Intelligent Design

Interesting proteins: DNA-binding proteins SATB1 and SATB2

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With this OP, I am starting a series (I hope) of articles whose purpose is to present interesting proteins which can be of specific relevance to ID theory, for their functional context and evolutionary history.

DNA-binding protein SATB1

SATB1 (accession number Q01826) is a very intriguing molecule. Let’s start with some information we can find at Uniprot, a fundamental protein database, about what is known of its function (in the human form):

Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma

And:

Transcriptional repressor controlling nuclear and viral gene expression in a phosphorylated and acetylated status-dependent manner, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes

IOWs, it is an important regulatory protein involved in many different, and not necessarily well understood, processes, which binds to DNA and in involved in chromatin remodeling.

It is also involved in hematopoiesis (especially in T cell development), and has important roles in the biology of some tumors:

Modulates genes that are essential in the maturation of the immune T-cell CD8SP from thymocytes. Required for the switching of fetal globin species, and beta- and gamma-globin genes regulation during erythroid differentiation. Plays a role in chromatin organization and nuclear architecture during apoptosis.

Reprograms chromatin organization and the transcription profiles of breast tumors to promote growth and metastasis.

Keywords for molecular function: Chromatin regulatorDNA-bindingRepressor

Now, some information about the protein itself. I will relate, again, to the human form of the protein:

Length: 763 AAs. It’s a rather big protein, like many important regulatory molecules.

Its subcellular location is in the nucleus.

It is a multi-domain protein, with at least 5 detectable domains and many DNA binding sites.

Evolutionary history of SATB1

Now, let’s see some features of the evolutionary history of this protein in the course of metazoa evolution.

I will use here the same tools that I have developed and presented in my previous OP:

The amazing level of engineering in the transition to the vertebrate proteome: a global analysis

So, I invite all those who are interested in the technical details to refer to that OP.

Here is a graph of the levels of homology to the human protein detectable in other metazoan groups, expressed as mean bitscore per aminoacid site:

 

Fig. 1: Evolutionary history of SATB1 by human-conserved functional information

 

The green line represents the evolutionary history of our protein, while the red dotted line is the reference mean line for the groups considered, as already presented in my previous post quoted above (Fig. 2).

As everyone can see, this specific protein has a very sudden gain in human-conserved information with the transition from pre-vertebrates to vertebrates. So, it represents a very good example of the information jump that I have tried to quantify globally in my previous post.

Here, the jump is of almost 1.5 bits per aminoacid site. What does that mean?

Let’s remember that the protein is 763 AA long. Therefore, an increase of information of 1.5 bits per aminoacid corresponds to more than 1000 bits of information. To be precise, the jump from the best pre-vertebrate hit to the best hit in cartilaginous fish is:

1049 bits

But let’s see more in detail how the jump happens.

I will show here in detail some results of protein blasts. All of them have been obtained using the Blastp software at the NCBI site:

https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome

with default settings.

Here is the result of blasting the human protein against all known protein sequences except for vertebrate sequences:

Fig. 2: Results of blasting human SATB1 against all non vertebrate protein sequences

 

As can be seen, we find only low homologies in non vertebrates, and they are essentially restricted to a small part of the molecule, that correspond to the first two domains in the protein, or just to the first domain. The image shows clearly that all the rest of the sequence has no detectable significant homologies in non vertebrates (except for a couple of very low homologies for the third domain).

The best hit in non vertebrates is 154 bits with Parasteatoda tepidariorum, a spider. Here it is:

Fig. 3: The best hit in non vertebrates (with a spider)

The upper line (Query) is the human sequence. The bottom line (Sbjct) is the aligned sequence of the spider. In the middle line, letters are identities, “+” characters are similarities (substitutions which are frequently observed in proteins, and are probably quasi-neutral), and empty spaces are less frequent substitutions, those that are more likely to affect protein structure and function if they happen at a functionally important aminoacid site.

The alignment here is absolutely restricted to AAs 71 – 245 (the first two domains), and involves only 177 AAs. Of these, only 78 (44%) are identities and 111 (62%) are positives (identities + similarities). So, in the whole protein we have only 78 identities out of 763 (10.2%).

The spider protein is labeled as “uncharacterized protein”, and that is the case in most of the other non vertebrate hits.

All the other non vertebrate hits, with a couple of exceptions, are well below 100 bits, most of them between 70 and 86 bits.

IOWs, the protein as we know it in vertebrates essentially does not exist in non vertebrates.

Even non vertebrate deuterostomia, which should be the nearest precursors of the first vertebrates, have extremely low homology bitscores with the human protein:

Saccoglossus kowalevskii (hemichordates):  87 bits

Branchiostoma floridae (cephalochordate): 67 bits

The information jump in vertebrates

Now, what happens with the first vertebrates?

The oldest split in vertebrates is the one between cartilaginous fish and bony fish (from which the human lineage derives). Therefore, homologies that are conserved between cartilaginous fish and humans had reasonably to be already present in the Last Common Ancestor of Vertebrates, before the split between cartilaginous fish and bony fish, and have been conserved for about 420 million years.

So, let’s see the best hit between the human protein and cartilaginous fish. It is with Rhincodon typus (whale shark). Here it is:

 

Fig. 4: The best hit of human SATB1 in cartilaginous fish (with the whale shark)

 

Here, the alignment involves practically the whole molecule (756 AAs), and we have 1203 bits of homology, 603 identities (79%), 659 positives (86%).

IOWs, the two molecules are almost identical. And the homology is extremely high not only in the domain parts, but also in the rest of the protein sequence.

Now, the evolutionary time between pre-vertebrates and the first split in vertebrates is certainly rather small, a few million years, or at most 20 – 30 million years. Not a big chronological window at all, in evolutionary terms.

However, in that window, this protein appears almost complete. 603 aminoacids are already those that will remain up to the human form of the protein, and only 78 of them were detectable in the best hit before vertebrate appearance.

1049 bits of new, original functional information. In such a short evolutionary window.

Functionality

Why functional? Because those 603 aminoacid have remained the same thorugh more than 400 million years of evolution. They have evaded neutral or quasi neutral variation, that would have certainly completely transformed the sequence in such a big evolutionary time, if those aminoacid sites were not under extreme functional constraint and purifying (negative) selection.

Now, I say that this fact cannot in any way be explained by any neo-darwinian model. Absolutely not.

Moreover, there is absolutely no evidence in the available proteome of any intermediate form, of any gradual development of the functional sequence that will be conserved up to humans (except, of course, for the 50 – 78 AAs which are already detectable in the first two domains in many pre -vertebrates).

By the way, Callorhincus milii, the Elephant shark, has almost identical values of homology:

1184 bits, 599 identities, 654 positives

But, how important is this protein?

In the ExAC database, a database of variations in the human genome, missense mutations are 110 out of 260.3 expected, with a z score of 4.56, an extremely high measure of functional constraint.

The recent medical literature has a lot of articles about the important role of SATB1 at least in two big fields:

  • T cell development
  • Tumor development (many different kinds of tumors)

If we want to sum up in a few words what is known, we could say that SATB1 is considered a master regulator, essentially a complex transcription repressor, involved mainly (but not only) in the development of the immune system, in particular T cells. A disregulation of this protein is linked to many aspects of tumor invasivity (especially metastases). The protein seems to act, among other possibilities, as a global organizer of chromatin states.

Here is a very brief recent bibliography:

Essential Roles of SATB1 in Specifying T Lymphocyte Subsets

SATB1 overexpression correlates with gastrointestinal neoplasms invasion and metastasis: a meta-analysis for Chinese population

SATB1-mediated Functional Packaging of Chromatin into Loops

DNA-binding protein SATB2

But there is more. There is another protein which is very similar to SATB1. It is called DNA-binding protein SATB2 (accession number Q9UPW6).

Its length is very similar to SATB1: 733 AAs.

Uniprot describes its function as follows:

Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes

Which is very similar to SATB1. But now come the differences. While SATB1 is implied prevalently in T cell development and tumor development, SATB2 is:

Required for the initiation of the upper-layer neurons (UL1) specific genetic program and for the inactivation of deep-layer neurons (DL) and UL2 specific genes, probably by modulating BCL11B expression. Repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex. May play an important role in palate formation. Acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation

So, similar proteins with rather different specificities. While SATB1 is mainly connexted to adaptive immunity (T cell development), SATB2 seems to be more linked to neuronal development. Like SATB1, it is involved in cancer development, although usually in different types of cancer.

Here is a brief recent bibliography about SATB2:

Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex

SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer

However, how similar is SATB2 to SATB1 in terms of sequence homology?

Here is a direct blast of the two human molecules:

 

Fig. 5: Blast of human SATB1 vs human SATB2:

 

OK, they are very similar, but…  only 460 identities, 550 positives, 854 bits. IOWs, these two human proteins are similar, but not so similar as the two sequences of SATB1 in the shark and in humans.

Now, here is the evolutionary history of SATB2:

 

Fig. 6: Evolutionary history of SATB2 by human-conserved functional information

 

As everyone can see, it is almost identical to the evolutionary history of SATB1. To see it even better, Fig. 7 shows the two evolutionary histories together (the green line is SATB1, the brown line is SATB2):

 

Fig. 7: Evolutionary history of SATB1 and SATB2 by human-conserved functional information

 

In particular, pre-vertebrate history and the jump in cartilaginous fish are practically identical. And yet these are two different molecules, as we have seen, with different specificities and about one third of difference in sequence.

Now, let’s blast human SATB2 against cartilaginous fish. Again the best hit is with the whale shark:

 

Fig. 8: The best hit of human SATB2 in cartilaginous fish (with the whale shark)

 

And the numbers are very similar, incredibly similar I would say, to those we found for SATB1:

1197 bits, 592 identities, 662 positives.

But what if we blast SATB1 of the whale shark against SATB2 of the whale shark?

Here are the results:

 

Fig. 9: Blast of whale shark SATB1 vs whale shark SATB2:

Now, please, compare the numbers we got here with those from the similar blast between the two proteins in humans:

SATB1 human vs SATB2 human:  460 identities, 550 positives, 854 bits

SATB1 shark vs SATB2 shark:      468 identities, 556 positives, 856 bits

Almost exactly the same numbers! Wow!

What does that mean?

It means that this system of two similar proteins with different function arises in vertebrates as a whole system, already complete, with the two components already differentiated, and is conserved almost identical up to humans. Indeed, SATB1 and SATB2 have the same degree of homology both in sharks and in humans, and the two SATB1 proteins in shark and humans, as well as the two SATB2 proteins in shark and humans, have greater similarity, after more than 400 million years of divergence, than SATB1 and SATB2 show when compared, both in sharks and in humans.

Would you describe that as sudden appearance of huge amounts of functional information, followed by an extremely long stasis? I certainly would!

The following table sums up these results:

Sequence 1 Sequence 2 Bitscore
SATB1 Human SATB2 Human 854
SATB1 Shark SATB2 Shark 856
SATB1 Human SATB1 Shark 1203
SATB2 Human SATB2 Shark 1197

IOWs, the whole system appeared practically as it is today, before the split of cartilaginous fish and bony fish, and has retained its essential form up to now.

So, the total amount of new functional information implied by the whole system of these two proteins is about 1545 bits (considering 855 bits of common information, and 345 bits x 2 of specific information in each molecule).

An amazing amount, for a system of just two molecules, considering that 500 bits is Dembski’s Universal Probability Bound!

Let’s remember that in my previous post, quoted above, I showed that the informational jump from pre-vertebrates to vertebrates is more than 1.7 million bits. That’s a very big number, but big numbers sometimes are not easily digested. So, I believe that seeing that just two important molecules can contribute for almost 1500 bits can help us understand what we are really seeing here.

Moreover, it’s certainly not a case that those two molecules seem to be fundamental in two very particular fields:

a) The adaptive immune system

b) The nervous system

if we consider that those are exactly the two most relevant developments in vertebrates.

And, as a final note, please consider that these are very complex master regulators, which interact with tens of other complex proteins to effect their functions. The whole system is certainly much more irreducibly complex than we can imagine.

But still, just the analysis of these two sister proteins is more than enough to demonstrate that the neo Darwinian paradigm is completely inappropriate to explain what we can see in the proteome and in its natural history. And this is only one example among thousands.

So, I want to conclude repeating again this strong and very convinced statement:

The observed facts described here cannot in any way be explained by any neo-darwinian model. Absolutely not. They are extremely strong evidence for a design inference.

305 Replies to “Interesting proteins: DNA-binding proteins SATB1 and SATB2

  1. 1
    kairosfocus says:

    GP, an article from you is always welcome, and the prospect of a series is even better. KF

  2. 2

    Excellent post. Thank you, thank you. The ending is priceless:

    “The observed facts described here cannot in any way be explained by any neo-darwinian model. Absolutely not. They are extremely strong evidence for a design inference.”

  3. 3
    gpuccio says:

    KF:

    Thank you!

    I am excited, too, by the prospect of a series. 🙂

    Let’s see what comes…

  4. 4
    gpuccio says:

    Truth Will Set You Free:

    Thank you for the kind comment, it is appreciated! 🙂

  5. 5
    Dionisio says:

    gpuccio,

    Glad to see a new insightful article from you. Thanks.

    As usual, very detailed and well illustrated.

  6. 6
    Dionisio says:

    A ton of information in this article for readers to process.

    I still haven’t chewed and digested the whole article.

    It’s heavily loaded with important information, literally causing a “Big Data” problem here. 🙂

    Let’s see how the discussion goes.

    Here’s science at its best. No reason for the politely dissenting interlocutors to whine again. Just come and discuss. Put aside the philosophical issues.

  7. 7
    Dionisio says:

    “The whole system is certainly much more irreducibly complex than we can imagine.”

    Making the amazing bacteria flagellum look like a Lego toy for toddlers. 🙂

  8. 8
    gpuccio says:

    Dionisio:

    “Making the amazing bacteria flagellum look like a Lego toy for toddlers.”

    Indeed. 🙂

    The fascinating thing is that we are still very far from understanding how such regulatory proteins work. I suppose that we still miss a lot about the role of chromatin remodeling, and 3D organization of DNA and RNA.

    I have found very interesting the video from AmNat by Sal Cordova posted by johhnyb, that deals with some of these aspects.

  9. 9
    RodW says:

    Thanks for the post. Its obvious you’ve put a lot of work into it.
    I disagree that this shows evidence for ID. While the protein is unique to vertebrates as you say, the domains that allow the protein to perform its function are not. In fact the CUT and HOX domains were discovered first in drosophila and the SATBIN domain is in flies as well. These domains are also part of larger families which perform similar functions.
    Ecclesiastes 1:9 says “there is nothing new under the sun” This reflects the fact that many of the things we at first think are new are really conglomerations of old things. This applies to many of the ‘novel’ proteins in vertebrates which are really just new combinations of old protein domains. This provides a good debating tactic for IDers. When we don’t know much about a new structure or protein it can be claimed that it required an infusion of information from an intelligent source. But when we discover how random genomic events could have created this new entity it can be dismissed as not really new.

    When one does a protein blast with humans one finds sharks with about 80% but as one gets closer to humans that number increases. The chimp protein is 100% identical. Its hard to explain why this would be the case for domains using ID since presumably the human HOX domain would work just as well in a shark. Its even harder for ID to explain the pattern of differences in the sequence between the domains since its function is to hold the domains together and an astronomically large number of aa sequences should suffice. Its also hard to explain why the pattern of difference would fit the same nested hierarchy build by assuming evolution from anatomy and the fossil record.

    The pattern of differences between SATB1 and SATB2 are fairly easy to explain and I admit I don’t understand why they suggest an irreducibly complex system as you say. An ancestral SATB gene would have duplicated in the vertebrate common ancestor. In each lineage the 2 genes would have accumulated differences starting from that initial divergence. When 2 lineages split from each other the SATB1 and SATB2 genes would then start to accumulate differences from their homolog in the other species. This is a pretty straightforward explanation that explains the pattern. I don’t see how one could explain the same pattern in terms of ID.

  10. 10
    gpuccio says:

    RodW:

    Thank you for your comments. Here are my answers:

    While the protein is unique to vertebrates as you say, the domains that allow the protein to perform its function are not. In fact the CUT and HOX domains were discovered first in drosophila and the SATBIN domain is in flies as well. These domains are also part of larger families which perform similar functions.

    As seen in Fig. 2, The SATB1_N and CUTL domains are the only two parts of the molecule which have any detectable homology in pre-vertebrates. I have clearly said it in my OP.

    I have never discussed if those domains are present, in different form, in other pre-vertebrate species. My analysis is based on sequences, and the sequence says that there is no relevant homology before vertebrates except for those that I have clearly mentioned and quantified.

    This is one of the most common biases of neo-darwinian thought. Those who reason as you are doing here are satisfied to detect any vague link between proteins in different species, sometimes only of structure, not even sequence, to rejoice and be sure that all is explained. But that is simply not true. ASome vague connection (which can certainly be present in many cases) does not explain the following jumps in information.

    Remember, I am not arguing that there is no contiuity in the proteome. I do believe that there is. I do believe in common descent, and indeed all my arguments are based on common descent. But common descent does not explain in any way the appearance of new huge amounts of functional information.

    Maybe you are missing the main point in my argument. I will try to be more clear.

    Human and sharks share in SATB1, after more than 400 million years, a conserved sequence of about 525 AAs (603-78) that was not at all detectable in all older species. These are functionally constrained AAS, because they are conserved for 400 million years. This specific sequence did not exist before. Can I be more clear than this?

    It’s not important if the domains, in different form, have been in some way identified before. I am not discussing the individual domains. I am discussing the functional sequence, because evolution through supposed RV happens in the space of sequences.

    More in next post.

  11. 11
    gpuccio says:

    RodW:

    Ecclesiastes 1:9 says “there is nothing new under the sun” This reflects the fact that many of the things we at first think are new are really conglomerations of old things.

    I don’t want to contradict Ecllesiastes, but do you mean that Shakespeare’s sonnets, or Windows 7, are just “conglomerations of old things”? Seriously, are you denying the informational novelty in designed things? Are humans the same thing as LUCA? Are E. coli and a fly the same thing, just “conglomerations of old things”? And the first living cells, were they just “conglomerations of old things”? Of stones and water and what else?

    This applies to many of the ‘novel’ proteins in vertebrates which are really just new combinations of old protein domains.

    Again, you make a gross error and oversimplification here.

    First of all, it is not true that there are no new domains in vertebrates. You certainly know that the appearance of new domains goes on throughout all natural history, even if at a constantly decreasing rate.

    But again, I am not discussing domains here.

    And do you really believe that a “new combinations of old protein domains” implies no new information?

    The domains, even when used in different proteins, are never the same. Their sequence changes a lot, and not only for neutral evolution, but also because domains are used differently in different proteins. Some similarity of sequence and structure and function does not mean that we are in front of the same thing.

    And, of course, the combination of new domains is in itself a huge bulk of new information, new planning, new purpose.

    Moreover, you seem to believe that all the parts of a protein between detectable domains are simply connections, almost useless. But that is completely wrong:

    a) We don’t know all domains, new ones are detected as our understanding gorws.

    b) A lot of interdomain sequences are extremely conserved, and certainly functional, as I have shown many times, including in this OP.

    c) You seem to ignore that a lot of proteins or protein parts are “intrinsically disordered” and lack a recognizable fixed structure, and yet they are very functional just the same.

    As I have clearly stated in my OP, in SATB1 and SATB2 the interdomain parts of the sequence are extremely conserved too, and therefore almost certainly functionally constrained.

    You seem to believe that proteins are just a collection of fixed modules in random order. But that is not the case. the connection between sequence and function in proteins is much more complex and in many cases still not well understood, and this is especially true for regulatory proteins, whose functional details still elude us. SAB1 and SATB2 certainly bind to DNA, but that is only the beginning of the story. In your reductionist approach, you seem to stop there.

    When we don’t know much about a new structure or protein it can be claimed that it required an infusion of information from an intelligent source. But when we discover how random genomic events could have created this new entity it can be dismissed as not really new.

    When we “discover how random genomic events could have created this new entity”?????

    Are you serious?

    Examples, please. I have been waiting for years!

    Just to start, why don’y you offer some thoughts about how “random genomic events could have created”, in a few million years, the new sequence of 525 functional AAs that did not exist before, and that was so successful that it was preserved by purifying selection for 400 million years afterwards?

    More in next post.

  12. 12
    Mung says:

    In fact the CUT and HOX domains were discovered first in drosophila and the SATBIN domain is in flies as well.

    The obvious conclusion is that flies evolved from humans.

  13. 13
    gpuccio says:

    RodW:

    When one does a protein blast with humans one finds sharks with about 80% but as one gets closer to humans that number increases. The chimp protein is 100% identical. Its hard to explain why this would be the case for domains using ID since presumably the human HOX domain would work just as well in a shark.

    You make some important errors here.

    Of course the homology, even if already high in sharks, continues to increase afterwards, up to the 100% or similar in primates. That is not difficult at all to explain, from an ID point of view.

    There are two different things that we must consider:

    a) Domains are not, as you seem to thing, rigid modules that will be always reused in the same way. They need to be adapted to each specific situation. That is true not only of domains, but of every biological structure.

    Many of the differences between species are obviously due to specific functional adjustments, even when the basic module is reused. A protein can be tweaked for a lot of reasons, like a different cell environment, different interactions, different regulations, and so on. Again, your idea of protein domains and of proteins in general is really rigid and simplistic.

    b) Neutral evolution happens, I absolutely believe that. That’s why I consider conserved sequences as functional only if they are separated by hundreds of millions of years.

    As I have explained in my previous post, neutral evolution can cancel practically all homologies from sequences that were the same at the beginning, provided that:

    1) Those sequences are not functional

    2) There is time enough for neutral evolution to happen.

    We know from the study of synonimous mutations in proteins that 400 million years are more than enough to ensure “saturation”, IOWs, that no homology can be detected between synonimous sites after that time.

    The thing is different, of course, for functionally constrained sites. That’s why our 600+ AAs are the same in shark and humans after more than 400 million years. That’s why such a conservation is a safe signature of functionality.

    But when we compare a sequence between humans and chimps, and we find 99% homology, we cannot really say if part of that homology is simply due to the fact that the twi lines diverged only a few million years ago: the time is too short.

    So, let’s say that with short chronological separations, we can expect some amount of “passive” homology, not corresponding to a true functional constraint.

    That’s why I have always used homologies between distant lineages to infer functional constraint.

    Its even harder for ID to explain the pattern of differences in the sequence between the domains since its function is to hold the domains together and an astronomically large number of aa sequences should suffice.

    Again, the same error, I have already discussed that. It is not true, absolutely not true, that the function of the sequence between the domains is to hold the domains together. Where did you get that strange idea? What are you proposing, that interdomain sequences are junk? 🙂

    More in next post

  14. 14
    gpuccio says:

    RodW:

    Its also hard to explain why the pattern of difference would fit the same nested hierarchy build by assuming evolution from anatomy and the fossil record.

    Why? I believe in common descent. Designed common descent. I have no problems with nested hierarchies. A lot of human designed artifacts fit in a natural nested hierarchy. What’s the problem?

    The pattern of differences between SATB1 and SATB2 are fairly easy to explain and I admit I don’t understand why they suggest an irreducibly complex system as you say.

    Really? Let’s see…

    An ancestral SATB gene would have duplicated in the vertebrate common ancestor. In each lineage the 2 genes would have accumulated differences starting from that initial divergence. When 2 lineages split from each other the SATB1 and SATB2 genes would then start to accumulate differences from their homolog in the other species. This is a pretty straightforward explanation that explains the pattern. I don’t see how one could explain the same pattern in terms of ID.

    Ah, I was really missing darwinian just so stories. It has been some time since someone offered some here in a discussion! 🙂

    So, let’s see. We have the original gene in the common ancestor. OK.

    What’s its function? What does it regulate? T cells or neurons?

    Nobody knows. Nobody will ever know.

    OK, but it duplicates. So, one of the copies goes on regulating T cells, or what else, and the other copy opts for neurons?

    No, wait, both copies accumulate differences. Because of neutral evolution, I suppose.

    So, after a short time, the two copies, in sharks, are a little different. They share only 468 identities, give or take, if we judge from the present proteome. At some point, however, that divergence stops. Those 468 identities remain for the following 400 million years.

    OK, you will say, we have reached the really functional core of 468 AAs. So, that is conserved.

    OK, say I, but then why in SATB1, if compared to human SATB1, the functional core which is conserved after 400 million years is of 603 AAs? And the same in SATB2?

    IOWs, as I have tried to explain in my OP, why is each single protein more conserved than what we see comparing the two proteins, both in humans and in sharks?

    The answer is simple enough: because the differences between SATB1 and SATB2, both in sharks and in humans, are not due to neutral evolution or divergence: they are functional. That’s why the differences are conserved for more than 400 million years, exactly like the similarities.

    IOWs, SATB1 and SATB2 share 468 AAs, give or take, because they do something in the same way, and are different for other 130 AAS, guve or take, because they do something else which is different.

    Because those 130 AAs are also functional, because in each protein those different 130 AAs are conserved, too, for more than 44 million years.

    Can you see my point?

    This is very easy to explain form a design point of view: the two sister proteins are designed together, as a whole system, probably starting form a similar precursor which is not yet functional. Then each of the two forms is specialized for different tasks, using the common basic sequence for the aspects which are shared in those tasks.

    That’s why I say that it is an irreducibly complex system. There is a common conception, and a very efficient differentiation. A very good design, which has performed well for a very long time.

    More in next post (the last one, I promise).

  15. 15
    gpuccio says:

    RodW:

    Well, I have said what I had to say. You will not be convinced, of course. I am well accustomed to that.

    Just one thing I want to add: I have really appreciated your comments.

    Indeed, what I really hope for when I publish my OPs, or simply my comments, is that some interlocutor from the other side will give intelligent and reasonable comments. That is the only way ideas can grow, and almost all my best ideas (if there are any) are the result of some passionate confrontation with my patient interlocutors.

    So, thank you again. 🙂

    (Of course, you are welcome to go on with your comments)

  16. 16
    gpuccio says:

    Mung:

    Of course flies evolved from humans. And beetles? 🙂

  17. 17
    Dionisio says:

    gpuccio:

    beetles evolved from Liverpool in the UK, though were spotted in Germany too, and later had several major random functional mutations:
    1. the sequence “The ” got added in the front.
    2. the ‘b’ changed to ‘B’ in the first position
    3. an ‘e’ changed to ‘a’ (3rd position)
    The whole change turned positive or advantageous and thus the mutated beetles became much louder The Beatles
    which were under selective pressure of wildly screaming crowds of teenagers 🙂

  18. 18
    Dionisio says:

    Well, RodW helped to heat up the discussion right after the thread started.

  19. 19
    gpuccio says:

    Dionisio:

    “beetles evolved from Liverpool in the UK,”

    That’s better than most neo darwinian just so stories 🙂

    “Well, RodW helped to heat up the discussion right after the thread started.”

    Yes, he was very kind, given the shortage of discussing opponents. And his arguments were stimulating. 🙂

  20. 20
    Dionisio says:

    Let’s repeat something important that gpuccio wrote @8:

    “The fascinating thing is that we are still very far from understanding how such regulatory proteins work. I suppose that we still miss a lot about the role of chromatin remodeling, and 3D organization of DNA and RNA.”

  21. 21
    RodW says:

    gpuccio

    I’ll try to write a substantial response in a few hours but I might have to wait till I can get to my work computer on Monday! My home computer is crap!

  22. 22
    Dionisio says:

    Let’s not forget that gpuccio has given us other long, well written and highly informative articles on this subject of functional specified information “somehow” added to proteins.

    This time he treats us with another deeply researched article, filled with technical data and analytical commentaries that shed much light on the important subject, while making it easier for the commoner laymen like myself to at least get an idea of the interesting situation that is presented. On top of this gpuccio promises a follow-up article.

    However, while trying to understand the significance of what is said in this thread, we should keep in mind the clever observation gpuccio wrote @8, which is quoted @20.

    All the complexity associated with the main idea proposed by gpuccio in his most recent articles –i.e. the inexplicable appearance of functional specified information in the analyzed proteins– is just the ‘antipasti’ in relation to what is implied by his comment @8, quoted @20.

    Let’s not be naïve. The deeper science looks into the biological systems, the more obvious the appearance of design is becoming, leading us to the logical realization that it’s much more than just appearance. We have no precedence to the marvelous informational systems seen in biology these days. The only things comparable are the sophisticated systems created by many scientists and engineers through cumulative knowledge and experience.

    Complex functional specified complexity.

    Whoever runs away from accepting that reality –which is increasingly supported by a growing avalanche of evidences– is surrendering to a philosophical worldview that is visibly doomed to becoming another shameful page of human history.

    We ain’t seen nothin’ yet.
    The most fascinating discoveries are still ahead.
    Work in progress… stay tuned.

  23. 23
    gpuccio says:

    RodW:

    I am looking forward to your interventions, and I hope that the discussion will go deeper and deeper. Please, take all the time that is necessary. 🙂

  24. 24
    gpuccio says:

    Dionisio at #22:

    How true, how true! 🙂

  25. 25

    gpuccio @ 10-15: Well done! I appreciate RodW’s challenging comments seeking understanding and truth. He clearly brings a lot to the table on this topic, and you responded admirably. I am learning a great deal from you both.

  26. 26
    kairosfocus says:

    Dionisio, do you mean complex, functionally specified information? KF

  27. 27
    gpuccio says:

    About SATB2:

    Just to understand what we are dealing with, here:

    Satb2 determines miRNA expression and long-term memory in the adult central nervous system. (November 2016)

    Abstract
    SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

    Link:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207769/pdf/elife-17361.pdf

  28. 28
    gpuccio says:

    SATB2 again:

    Satb2 Stations Neurons along Reflex Arcs. (2016)

    Abstract
    The nociceptive flexor withdrawal reflex has an august place in the history of neuroscience. In this issue of Neuron, Hilde et al. (2016) advance our understanding of this reflex by characterizing the molecular identity and circuit connectivity of component interneurons. They assess how a DNA-binding factor Satb2 controls cell position, molecular identity, pre-and postsynaptic targeting, and function of a population of inhibitory sensory relay interneurons that serve to integrate both proprioceptive and nociceptive afferent information.

    And:

    Satb2 Is Required for the Development of a Spinal Exteroceptive Microcircuit that Modulates Limb Position. (2016)

    Abstract
    Motor behaviors such as walking or withdrawing the limb from a painful stimulus rely upon integrative multimodal sensory circuitry to generate appropriate muscle activation patterns. Both the cellular components and the molecular mechanisms that instruct the assembly of the spinal sensorimotor system are poorly understood. Here we characterize the connectivity pattern of a sub-population of lamina V inhibitory sensory relay neurons marked during development by the nuclear matrix and DNA binding factor Satb2 (ISR(Satb2)). ISR(Satb2) neurons receive inputs from multiple streams of sensory information and relay their outputs to motor command layers of the spinal cord. Deletion of the Satb2 transcription factor from ISR(Satb2) neurons perturbs their cellular position, molecular profile, and pre- and post-synaptic connectivity. These alterations are accompanied by abnormal limb hyperflexion responses to mechanical and thermal stimuli and during walking. Thus, Satb2 is a genetic determinant that mediates proper circuit development in a core sensory-to-motor spinal network.

    Satb2 Regulates the Differentiation of Both Callosal and Subcerebral Projection Neurons in the Developing Cerebral Cortex. (2015)

    Abstract
    The chromatin-remodeling protein Satb2 plays a role in the generation of distinct subtypes of neocortical pyramidal neurons. Previous studies have shown that Satb2 is required for normal development of callosal projection neurons (CPNs), which fail to extend axons callosally in the absence of Satb2 and instead project subcortically. Here we conditionally delete Satb2 from the developing neocortex and find that neurons in the upper layers adopt some electrophysiological properties characteristic of deep layer neurons, but projections from the superficial layers do not contribute to the aberrant subcortical projections seen in Satb2 mutants. Instead, axons from deep layer CPNs descend subcortically in the absence of Satb2. These data demonstrate distinct developmental roles of Satb2 in regulating the fates of upper and deep layer neurons. Unexpectedly, Satb2 mutant brains also display changes in gene expression by subcerebral projection neurons (SCPNs), accompanied by a failure of corticospinal tract (CST) formation. Altering the timing of Satb2 ablation reveals that SCPNs require an early expression of Satb2 for differentiation and extension of the CST, suggesting that early transient expression of Satb2 in these cells plays an essential role in development. Collectively these data show that Satb2 is required by both CPNs and SCPNs for proper differentiation and axon pathfinding

    Link:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585495/pdf/bhu156.pdf

  29. 29
    gpuccio says:

    SATB1:

    Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. (2017)

    Abstract
    Most Foxp3+ regulatory T (Treg) cells develop in the thymus as a functionally mature T cell subpopulation specialized for immune suppression. Their cell fate appears to be determined before Foxp3 expression; yet molecular events that prime Foxp3- Treg precursor cells are largely obscure. We found that Treg cell-specific super-enhancers (Treg-SEs), which were associated with Foxp3 and other Treg cell signature genes, began to be activated in Treg precursor cells. T cell-specific deficiency of the genome organizer Satb1 impaired Treg-SE activation and the subsequent expression of Treg signature genes, causing severe autoimmunity due to Treg cell deficiency. These results suggest that Satb1-dependent Treg-SE activation is crucial for Treg cell lineage specification in the thymus and that its perturbation is causative of autoimmune and other immunological diseases.

    And:

    SATB1 Plays a Critical Role in Establishment of Immune Tolerance. (2016)

    Abstract
    Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that is expressed by T cells. T cell development is severely impaired in SATB1 null mice; however, because SATB1 null mice die by 3 wk of age, the roles of SATB1 in T cell development have not been well clarified. In this study, we generated and analyzed SATB1 conditional knockout (cKO) mice, in which the SATB1 gene was deleted from all hematopoietic cells. T cell numbers were reduced in these mice, mainly because of a deficiency in positive selection at the CD4(+)CD8(+) double-positive stage during T cell development in the thymus. We also found that SATB1 cKO mice developed autoimmune diseases within 16 wk after birth. In SATB1 cKO mice, the numbers of Foxp3(+) regulatory T (Treg) cells were significantly reduced at 2 wk of age compared with wild-type littermates. Although the numbers gradually increased upon aging, Treg cells in SATB1 cKO mice were still less than those in wild-type littermates at adulthood. Suppressive functions of Treg cells, which play a major role in establishment of peripheral tolerance, were also affected in the absence of SATB1. In addition, negative selection during T cell development in the thymus was severely impaired in SATB1 deficient mice. These results suggest that SATB1 plays an essential role in establishment of immune tolerance.

    Link: http://www.jimmunol.org/content/196/2/563.full.pdf

  30. 30
    gpuccio says:

    The articles quoted in my last posts fully confirm the role of SATB1 and SATB2 as critical super-regulators.

    These are obviously very important proteins, at the center of complex networks.

    They probably bind DNA in a similar way, especially at so called matrix attachment regions (MARs), and induce a local chromatin-loop remodeling.

    But what happens after the DNA binding, and in what cells and context it happens, is dramatically different for the two molecules.

    This is the rule for regulatory proteins and, in general, transcription factors. They do bind DNA, but the specificity of their regulatory action is given by the further interactions and bindings with many other complex molecules. TFs often act in macro-complexes that include even 10-15 proteins, or more. And the key to the effect is, very often, a modification of chromatin structure, often generating new loops that bring together distant genes that need to interact, especially enhancers.

    Are these regulatory systems irreducibly complex?

    Of course they are. The specificity of the regulation depends critically on the interaction of many complex agents. This kind of system is even more irreducibly complex than a protein cascade, like the famous coagulation cascade quoted by Behe in Darwin’s Black Box, because a cascade, although of course irreducibly complex, is in some way a linear connection of enzymatic activities, whose purpose is the amplification and regulation of a process that yields a final product.

    The regulatory networks we are dealing with here, instead, are complex 3D networks of interactions, with many more dimensions than a “simple” cascade. Chromatin 3D structure is a complex and flexible space of states, that we still understand only marginally. And the states of DNA from the point of view of biophysics are probably even more complex and elusive.

    We are here in the full domain of epigenetics, which is daily revealing itself as the master controller of all cell processes.

    With this kind of molecules, we are exactly at the core of the problem, of its mystery and fascination.

  31. 31
    john_a_designer says:

    It has been fashionable for those on the ID side to highlight (the critics would say quote-mine) the following quote from Richard Lewontin’s 1997 NYT review of Carl Sagan’s book, The Demon-Haunted World: Science as a Candle in the Dark.

    We take the side of science in spite of the patent absurdity of some of its constructs, in spite of its failure to fulfill many of its extravagant promises of health and life, in spite of the tolerance of the scientific community for unsubstantiated just-so stories, because we have a prior commitment, a commitment to materialism. It is not that the methods and institutions of science somehow compel us to accept a material explanation of the phenomenal world, but, on the contrary, that we are forced by our a priori adherence to material causes to create an apparatus of investigation and a set of concepts that produce material explanations, no matter how counter-intuitive, no matter how mystifying to the uninitiated. Moreover, that materialism is absolute, for we cannot allow a Divine Foot in the door.

    Indeed, Lewontin is to be commended for his honesty, for being up front about his philosophical biases. On the other hand, he provides absolutely no justification for his philosophical beliefs. Because Richard Lewontin believes something doesn’t make it true for everyone else. He just asserts without argument that scientific explanations based on materialism are for some reason absolute. According to what standard? Indeed, he contradicts the criticism he made just a few paragraphs earlier of his fellow Darwinists.

    As to assertions without adequate evidence, the literature of science is filled with them, especially the literature of popular science writing. Carl Sagan’s list of the “best contemporary science-popularizers” includes E.O. Wilson, Lewis Thomas, and Richard Dawkins, each of whom has put unsubstantiated assertions or counterfactual claims at the very center of the stories they have retailed in the market. Wilson’s Sociobiology and On Human Nature rest on the surface of a quaking marsh of unsupported claims about the genetic determination of everything from altruism to xenophobia. Dawkins’s vulgarizations of Darwinism speak of nothing in evolution but an inexorable ascendancy of genes that are selectively superior, while the entire body of technical advance in experimental and theoretical evolutionary genetics of the last fifty years has moved in the direction of emphasizing non-selective forces in evolution. Thomas, in various essays, propagandized for the success of modern scientific medicine in eliminating death from disease, while the unchallenged statistical compilations on mortality show that in Europe and North America infectious diseases, including tuberculosis and diphtheria, had ceased to be major causes of mortality by the first decades of the twentieth century, and that at age seventy the expected further lifetime for a white male has gone up only two years since 1950. Even The Demon-Haunted World itself sometimes takes suspect claims as true when they serve a rhetorical purpose as, for example, statistics on child abuse, or a story about the evolution of a child’s fear of the dark.

    I wholeheartedly agree. Just-so stories are never adequate. The honest answer when we don’t know is to honestly admit that we don’t know.

    With that said, I don’t think that the discussion here with Rob W. is going to go anywhere, because he is going to stick tenaciously to his just-so stories rather than admit that he just doesn’t know. The natural scientific theories need to be built on factually established evidence, not Darwin of the gaps just-so-stories.

  32. 32
    gpuccio says:

    john_a_designer:

    Thank you for your comments. I agree.

    The problem is that darwinists have become so accustomed to “explain” things by just building a narrative compatible with their theory, that they really believe, after decades of absolute power in the academy, that building a narrative is an explanation.

    They are not bothered by the complete absence of empirical support to their narratives. They are not bothered by the mathematical and probabilistic impossibilities implicit in the theory itself. A narrative is an explanation, provided that it is their won narrative, and that it supports their own theory.

    But an explanation is all another thing. An explanation must contribute to our understanding, must be formally appropriate, must correspond to what facts are saying.

    Let’s compare these two statements:

    a) These two proteins are complex master regulators. They share a lot of functional specificity, including the ability to bind DNA at some specific region, and they share a great part of their sequence, of course to implement those common functionalities. At the same time, they use those common functionalities to effect some fine regulation of completely different networks, and therefore there is a relevant part of the functional information conserved in each protein which differs in the two proteins. We are seeing a clear example of modular design, with differentiated functions, which implies the careful selection of long and specific AA sequences, for a total functional complexity of about 1500 bits, well beyond the range of any non design explanation.

    b) The pattern of differences between SATB1 and SATB2 are fairly easy to explain and I admit I don’t understand why they suggest an irreducibly complex system as you say. An ancestral SATB gene would have duplicated in the vertebrate common ancestor. In each lineage the 2 genes would have accumulated differences starting from that initial divergence. When 2 lineages split from each other the SATB1 and SATB2 genes would then start to accumulate differences from their homolog in the other species. This is a pretty straightforward explanation that explains the pattern. I don’t see how one could explain the same pattern in terms of ID.

    Everyone can decide for himself how these explanations match the facts.

    However, I don’t think that “the discussion here with RodW is going to go nowhere”. It has already been precious, allowing me (and others) to express our arguments, and I really hope that RodW will express further thoughts from his point of view, and I really hope that they will be quality thoughts, because only quality thoughts can really evoke quality answers. 🙂

    After all, the purpose is not to convince anyone, but rather to express good ideas about important stuff.

  33. 33
    Mung says:

    So, gpuccio, you don’t believe that evolution works by mixing and matching protein domains in order to see what new and useful arrangements might arise?

    Sort of like a 6 year old with a nice assortment of LEGO parts.

  34. 34
    gpuccio says:

    Mung:

    No, I don’t believe it, as you probably know… 🙂

    Domains are an important concept, and an useful way to classify functional units according to sequence similarity, structure similarity and function similarity.

    But we must look at them for what they are: a gross categorization.

    If we think of them as fixed, rigid modules, we miss the point: it’s just oversimplification.

    Categorization is the grouping of different things according to some common trait. But we must remember that they are different things.

    Our understanding of protein structure is gross at best. We analyze proteins as a medical examiner analyzes a corpse. We know little of how proteins really work.

    Domain homology has been vastly used by darwinists to trace connection throughout evolutionary history. That’s fine. But connections are not explanations. Sequences change and sequences are conserved. both in domains and outside of them. Some changes are functional, others certainly are not. But it is difficult to discriminate.

    I have always tried to emphasize that differences often tell more than homologies. It’s the sum total of differences and homologies that can reveal the general plan, provided that we don’t look at it through the eyes of ideology.

    Darwinists love to oversimplify things, because their theory hates too much complexity.

    But really, do you think that LEGO could be satisfactorily explained by a darwinist context? 🙂

  35. 35
    Dionisio says:

    Insightful quote:

    “Categorization is the grouping of different things according to some common trait. But we must remember that they are different things.”

  36. 36
    Dionisio says:

    Insightful quote:

    “Our understanding of protein structure is gross at best. We analyze proteins as a medical examiner analyzes a corpse. We know little of how proteins really work.”

  37. 37
    Dionisio says:

    KF @26:
    Yes, good catch! Thank you!

    But perhaps complex, functionally specified informational complexity could go along with the intentionally redundant phrase “complex complexity” too.
    🙂

  38. 38
    Dionisio says:

    gpuccio @30:

    “The specificity of the regulation depends critically on the interaction of many complex agents.”

  39. 39
    Dionisio says:

    gpuccio @32:

    “An explanation must contribute to our understanding, must be formally appropriate, must correspond to what facts are saying.”

  40. 40
    Dionisio says:

    gpuccio,

    Here’s a quasi-dumb question, which maybe has been answered in your text, or it’s related to basic knowledge which is assumed as prerequisite to understand the discussed subject.

    Do the regulatory proteins that you refer to in your OPs are the product of associated genes expressed through the central dogma procedure –i.e. straightforward transcription + translation of given genes– or the product of pleiotropic DNA material processed through alternative splicing and post-translational modifications, or all of the above + something else?

    Does the additional information in the given proteins correspond to additional information in the DNA too?

    Do my questions make sense?

    I could try to rephrase the questions if they are not clear.

    Thank you.

  41. 41
    Dionisio says:

    gpuccio,

    I just realized that my reference to genetic pleiotropic effect @40 is incorrect, because that concept has to do with phenotypic traits, not exactly with proteins resulting from gene expression.

    Mea culpa. I know you’re a forgiving teacher, specially to the more disadvantaged students.

    Nevertheless, the questions @40 remain open.

  42. 42
    Dionisio says:

    Does this have any relation at all to the discussed topic?

    Gene set selection via LASSO penalized regression (SLPR).
    Frost HR, Amos CI
    Nucleic Acids Res. 2017 May 2.
    doi: 10.1093/nar/gkx291

    Gene set testing is an important bioinformatics technique that addresses the challenges of power, interpretation and replication. To better support the analysis of large and highly overlapping gene set collections, researchers have recently developed a number of multiset methods that jointly evaluate all gene sets in a collection to identify a parsimonious group of functionally independent sets. Unfortunately, current multiset methods all use binary indicators for gene and gene set activity and assume that a gene is active if any containing gene set is active. This simplistic model limits performance on many types of genomic data. To address this limitation, we developed gene set Selection via LASSO Penalized Regression (SLPR), a novel mapping of multiset gene set testing to penalized multiple linear regression. The SLPR method assumes a linear relationship between continuous measures of gene activity and the activity of all gene sets in the collection. As we demonstrate via simulation studies and the analysis of TCGA data using MSigDB gene sets, the SLPR method outperforms existing multiset methods when the true biological process is well approximated by continuous activity measures and a linear association between genes and gene sets.

    Thanks.

  43. 43
    gpuccio says:

    Dionisio:

    Good questions, and certainly not easy to answer.

    I have checked the AspicDB, a database for alternative splicing and alternative transcripts.

    19 alternative transcripts are described for SATB1, only 3 for SATB2. I believe these are not exceptional values.

    Of course, some forms of post-transcriptional modifications are mentioned, too, in Uniprot, but again nothing special IMO.

    So, I would say that these are not exceptional proteins from that point of view.

    The question of how alternative trancripts are regulated and functionally used in different contexts remains, IMO, vastly unsolved. Maybe you can offer some literature reference, if you happen to find it in your remarkable activity of literature search and filtering. 🙂

    I would think that much of the “pleiotropism” of possible regulatory functions of these master regulators is already intrinsic in the protein itself, and in its ability to interact differently with its fellow proteins in different situations and cell contexts. But this is only my personal opinion.

    I don’t know if I have really answered your questions. You are welcome to clarify better your point of view, of course. Your contribution and support is always greatly appreciated. 🙂

  44. 44
    gpuccio says:

    Dionisio:

    OK, we could probably say “polymorphism” instead of “pleiotropism”, but I think we understand well what we are speaking of.

    Regarding the LASSO, paper, I really don’t know, it seems very technical. I should read it carefully to just try to understand what they are speaking of! 🙂

  45. 45
    john_a_designer says:

    gpuccio:

    However, I don’t think that “the discussion here with RodW is going to go nowhere”. It has already been precious, allowing me (and others) to express our arguments, and I really hope that RodW will express further thoughts from his point of view, and I really hope that they will be quality thoughts, because only quality thoughts can really evoke quality answers.

    Unfortunately, the track record for most of our naturalist/materialist interlocutors here has been poor to very poor. They mistake obfuscation and obstruction, pretension and posturing, or just being argumentative with sound reasonable evidence based arguments. In other words, we’re arguing about a particular mechanism “A” they’ll come back with well what about this, this and that– B, C, or D… Never mind that B, C or D have little or nothing to do with A.

    For example, in discussions about irreducible complexity I have had committed Darwinists try to argue that common descent not only refutes IR but is strong evidence that natural selection acting on random variation is the ubiquitous driver of evolution. Never mind the fact that ID’ists like Behe and Denton accept CD. (For some reason they just ignore that fact.) Never mind, that no one can explain step-by-step-step how an apparently IC mechanism is “planned”* and constructed by a mindless natural process. (*Of course, by planned we can only mean the appearance of being planned.)

    As a real life machine designer (now retired) I’d like to know how that is done. Isn’t the point of natural empirical science to explain HOW something originated?

  46. 46
    J-Mac says:

    I think that Ecclesiastes 1:9 has to be looked at in the context of what Solomon was writing about-the lack of purpose and meaning of life without God, that he came to realize after exploring the countless pursuits…

    New things were being invented and built during his life and he was the leader of that…and yet none of his projects or pursuits brought him lasting satisfaction…”…everything is vanity…”-he often reflected.

    From the prospect of quantum information conservation, no quantum information is created or lost…so if no quantum information is created or lost…quantum states of subparticles are just being re-arranged due to the laws of quantum mechanics…

    So in that sense, one can say that “…there is nothing new under the sun…”..

    Everything is just a re-arrangements of the ever existing stuff thanks to the existence of physical laws that allow for that..

  47. 47
    gpuccio says:

    J-Mac:

    Of course Ecclesiastes meant a different thing.

    I really believe that there is nothing really new under the sun, because in the end we all borrow, in some way, from God’s mind, but it is also true that, as independent agents, we are creative, and can use ideas in a personal, original way. So, things can be new and old at the same time.

    For the nth time, I feel compelled to quote my favourite Shakespeare’s sonnet:

    Why is my verse so barren of new pride,
    So far from variation or quick change?
    Why with the time do I not glance aside
    To new-found methods, and to compounds strange?
    Why write I still all one, ever the same,
    And keep invention in a noted weed,
    That every word doth almost tell my name,
    Showing their birth, and where they did proceed?
    O know, sweet love, I always write of you,
    And you and love are still my argument,
    So all my best is dressing old words new,
    Spending again what is already spent:
    For as the sun is daily new and old,
    So is my love still telling what is told.

    (emphasis mine! 🙂 )

    I think this could be one of the meanings of Ecclesiastes. However, it’s a concept that I deeply feel to be true.

    Ah, if only more people were able to “tell what is told” in the absolutely original and transcendent way Shakespeare did!

  48. 48
    gpuccio says:

    john_a_designer at #45:

    I can agree wholeheartedly with what you say here!

    I have been in similar contexts many times.

    And, being one of the IDists who explicitly accept CD, I must say that I have been in similar contextx with some of our friends here, too! 🙂

    However, I would like to say that some of our interlocutors are different. Not in the sense that they can be convinced of the value of at least some of our ideas: that’s probably too much to be expected, after all these people have a dogmatic commitment to their worldview, and it is very unlikely that they can accept any idea that, in their opinion, can really challenge that world-view. In the end, I must say that I have never seen any interlocutor accept even a tiny part of the obvious truths in ID thought. If they did, there would be no limit to what could happen… 🙂

    But some of them are good interlocutors, indeed. Not many, unfortunately, but some really are.

    A good interlocutor, IMO, must have at least the following two qualities:

    1) He must be intelligent, and precise in the discussion, and pertinent to what is being discussed. IOWs, he must not play tricks (or at least, not so often! 🙂 )

    2) He must be honestly interested in an intellectual confrontation. IOWs, he must like ideas, and interesting arguments, not for their sake, but because of some inherent respect for truth and reality.

    OK, have we met interlocutors who, more or less, not necessarily perfectly, met those requirements?

    I believe we have. Not many, not often, but one once in
    while can be enough.

    I have often praised some of them here. I don’t want to make names here, because I have forgotten many of them. I will only quote two “classics”, just to give an idea:

    Mark Frank, for his constant honesty

    Zachriel, because he is often brilliant

    But I had very deep and satisfying discussions with many others, especially in the past.

    It is rather obvious that those commenters are somewhat lacking here, at present. Except for Bob O’H, always serious, but rather shy, I have not seen much recently (if we don’t want to consider the generous, but rather idiosyncratic interventions of rvb8). I don’t know the reasons, maybe they were banned, or they are simply tired of the discussion.

    Whatever the reason, it’s a pity that we don’t have more like them.

  49. 49
    Dionisio says:

    gpuccio:
    Yes, your comment @43 helps me to understand how to approach the given topic. Thank you for the information. As per your suggestion, I’ll try to keep an eye on papers covering that topic, so we can share them here.

    Regarding your comment @44, yes, I agree that’s “polymorphism” instead of “pleiotropism”.
    Thank you for the correction.

    The more we know, more is there for us to learn.

  50. 50
    gpuccio says:

    Dionisio:

    “The more we know, more is there for us to learn.”

    Absolutely true!

  51. 51
    J-Mac says:

    gpuccio,

    “I really believe that there is nothing really new under the sun, because in the end we all borrow, in some way, from God’s mind, but it is also true that, as independent agents, we are creative, and can use ideas in a personal, original way. So, things can be new and old at the same time.

    Right on! I couldn’t agree more especially when we consider the free will/consciousness connection. You are so right about the mind of God, because although we can and should be creative and hopefully become wiser, we will never surpass the mind or wisdom of God…

    Shakespeare rocks! 🙂

  52. 52
    gpuccio says:

    J-Mac:

    “Shakespeare rocks!”

    He is the best! 🙂

  53. 53
    Dionisio says:

    J-Mac,
    Off-topic comment regarding your mentioning an OT book.

    Here’s a late 20th century Spanish secular version of Ecclesiastes:

    Lo tengo todo,
    completamente todo;
    mil amigos y amores
    y el aplauso en la noche.

    Lo tengo todo,
    completamente todo;
    voy por la vida
    rodeado de gente
    que siento mia.
    Voy de abrazo en abrazo,
    de beso en risa,
    me dan la mano,
    cuando es precisa;
    la loca suerte
    besa mi frente
    por donde voy.
    Pero cuando amanece,
    y me quedo solo,
    siento en el fondo
    un mar vacío,
    un seco río,
    que grita y grita
    que sólo soy
    un hombre solo,
    un hombre solo,
    un hombre solo.

    Basically someone who tried practically everything under the sun but got no satisfaction at the end of the day.
    What else is new?
    There were other famous secular versions of that OT book in the late 20th century:
    The Eagles – Hotel California
    Rolling Stones – Satisfaction
    Pink Floyd – Time
    Led Zeppelin – Stairway to Heaven
    And not so famous:
    Mashina Vremeny – ty ili ya
    Czerwone Gitary – Nie spoczniemy
    Basically a lost world desperately searching for the true meaning of life to no avail.

  54. 54
    Dionisio says:

    J-Mac,
    Here’s Mashina Vremeny – Ty ili ya:
    https://www.youtube.com/embed/qXvpGZvL8B8
    If you want, I can translate it for you.
    I heard them live in Sochi by the Black Sea in the mid ’70s!
    IL TEMPO VOLA!
    That’s it. Enough off topic digressions. Let’s get back to discuss the interesting topic of complex functionally specified information “somehow” added to proteins.
    This week RodW should come back to present his challenging ideas to gpuccio.
    I’m sure our beloved Italian doctor can sweep and mop the floor with any “challenging” ideas the politely dissenting interlocutors may present to him here.
    But still it must be interesting to watch such a debate.
    Get ready, it may start tomorrow.
    🙂

  55. 55
    gpuccio says:

    Dionisio, RodW and whoever may be interested:

    I would like to add a few words here to make more clear my point about the specificity of SATB1 vs SATB2.

    If we look at the alignment of the two human proteins, in Fig. 5, we can choose a segment where the homology is low.

    For example, I have taken the segment including AAs 242-312 of SATB1 (the one starting with HFKKT), which are aligned to the segment including AAs 228 – 299 of SATB2 (the one starting with KYKKI). That includes the final part of the second domain, and an interdomain sequence.

    Well, even if this part of the two molecules still shows some significant homology, it is definitely lower than the average homology of the two proteins as a whole. Blasting those two segments only, the result is:

    Bitscore: 24.6 bits
    Expect: 4e-04
    Identities: 27/74(36%)
    Positives: 35/74(47%)

    OK, the homology is significant, even for this short tract, but it is rather low.

    But, if we blast the same SATB1 segment against the whale shark SATB1, like in Fig. 4, we get:

    Bitscore: 100 bits
    Expect: 4e-26
    Identities: 51/75(68%)
    Positives: 57/75(76%)

    And if we blast the corresponding segment of SATB2 against the whale skark SATB2, like in Fig. 8, we get, similarly:

    Bitscore: 104 bits
    Expect: 1e-27
    Identities: 53/87(61%)
    Positives: 64/87(73%)

    The Expect value, which is a measure of the probability of finding such a homology by chance, goes down of about 22 orders of magnitude (4e-26, 1e-27) in the direct confrontation of the two SATB1 or the two SATB2 segments, while it is only of the order of 10e-4 if we confront SATB1 with SATB2 (always for this short segment).

    The only possible explanation is that this segment, which is largely interdomain, is highly specific for the two different functionalities of SATB1 and SATB2: it is tailored in each of the two molecules for specific functional reasons, and it retains only low basic homology when we compare the two different sister molecules in humans (or even in sharks, as can be seen in Fig.9).

    This reasoning is the same that I have given in the OP, but I thought that perhaps, by focusing on one short segment where the difference between SATB1 and SATB2 is apparent, the argument could be understood better.

    It also strongly supports the importance of specific interdomain sequences.

  56. 56
    Dionisio says:

    gpuccio,

    “The only possible explanation is that this segment, which is largely interdomain, is highly specific for the two different functionalities of SATB1 and SATB2”

    Hmm… Interesting observation.

    It also strongly supports the importance of specific interdomain sequences.

    More food for thoughts. Thanks.

    Let’s see what RodW has to say on this.
    Maybe someone else out there has a counter-argument?

    I have a few questions:

    Have you seen a similar research published out there?

    Have you considered publishing your conclusions along with this enormous amount of interesting data your research effort has produced?

    Have you contacted a journal?

    I’m having in mind your latest 3 OPs combined, though it might be too long for one single article.

    Maybe remove any ID reference so that it looks more politically correct thus increasing the odds of being accepted in a peer-reviewed journal? Also add a couple of “surprisingly” and “unexpectedly” to make it appear like a neo-Darwinian archaic pseudoscientific nonsense. Then it might be accepted right away. At least it should pass the peer reviews, because it will sound like music to their ears. 🙂

  57. 57
    Dionisio says:

    gpuccio,

    This is serious research you have presented here, as well as in the previous two OPs on related subject. I commend you for this effort. Thanks.

    Since this discussion is about the appearance of new information in the proteins SATB1 and SATB2, it may help to understand well how the information gets to SATB1 and SATB2 to begin with.

    Perhaps there are some readers who find this discussion interesting, but feel lost regarding certain basic technical concepts that are assumed as prerequisites for this discussion.

    I’ve asked this before, but after going through your answers, I still need help to understand a few basic concepts.

    When you BLAST the proteins SATB1 and SATB2 and analyze them, giving numbers that indicate relative positions within the proteins and their domains, what does that tell us about the actual DNA genetic information that was expressed into the given proteins?

    Where should one look to get a very simplified description of the DNA segments (containing introns + exons) that are transcribed into the corresponding mRNA molecules that are later translated by the ribosome machinery into the proteins SATB1 and SATB2? Basically, where in the DNA are the codons taken from? Is there an easy to understand map showing their relative locations within the DNA (i.e. chromosome number + relative position within the given chromosome)?

    You pointed to the databases where that is shown, but my ignorance level does not let me get the simplified picture of this basic sequential step-by-step process that is according to the central dogma of biology: DNA makes RNA makes Protein. As you pointed out before, some polymorphism might be included too.

    Would you find some time to write an OP explaining this for SATB1 and SATB2? It could be considered a complement material to this current thread.

    Please, correct any misconception or misrepresentation in this comment.

    Thank you.

  58. 58
    Dionisio says:

    gpuccio,

    You wrote this:

    Evolutionary history of SATB1 by human-conserved functional information

    the jump from the best pre-vertebrate hit to the best hit in cartilaginous fish is: 1049 bits

    the protein as we know it in vertebrates essentially does not exist in non vertebrates.

    The information jump in vertebrates

    Now, the evolutionary time between pre-vertebrates and the first split in vertebrates is certainly rather small, a few million years, or at most 20 – 30 million years. Not a big chronological window at all, in evolutionary terms.

    However, in that window, this protein appears almost complete. 603 aminoacids are already those that will remain up to the human form of the protein, and only 78 of them were detectable in the best hit before vertebrate appearance.

    1049 bits of new, original functional information. In such a short evolutionary window.

    this fact cannot in any way be explained by any neo-darwinian model.

    gpuccio, you also wrote this:

    Evolutionary history of SATB1 and SATB2 by human-conserved functional information

    this system of two similar proteins with different function arises in vertebrates as a whole system, already complete, with the two components already differentiated, and is conserved almost identical up to humans.

    Would you describe that as sudden appearance of huge amounts of functional information, followed by an extremely long stasis? I certainly would!

    the whole system appeared practically as it is today, before the split of cartilaginous fish and bony fish, and has retained its essential form up to now.

    the total amount of new functional information implied by the whole system of these two proteins is about 1545 bits

    the informational jump from pre-vertebrates to vertebrates is more than 1.7 million bits.

    The observed facts described here cannot in any way be explained by any neo-darwinian model. Absolutely not. They are extremely strong evidence for a design inference.

    So how is this explained in the biology textbooks?

    Do they say it happened through the so called co-option or something like that?

    Do they leave it as a temporary knowledge gap to be filled later when technology improves and science can get better information on how things could happen?

    Do they ignore it or skip over it as if nothing important happened?

  59. 59
    Dionisio says:

    RodW should appear with his challenging comments anytime, that’s why I wanted to get my questions in first. 🙂

  60. 60
    Dionisio says:

    Isn’t it ironic that the whining politely dissenting interlocutors don’t join this discussion to present their strong arguments?

    Their absence is suspicious, isn’t it?

    Don’t they like serious scientific discussions?

    Can it get more serious and scientific than this?

    Right now their nonsense comments are seen in other threads.

  61. 61
    gpuccio says:

    Dionisio:

    “Have you seen a similar research published out there?”

    Not that I am aware of.

    “Have you considered publishing your conclusions along with this enormous amount of interesting data your research effort has produced?

    “Have you contacted a journal?”

    No.

    “”Maybe remove any ID reference so that it looks more politically correct thus increasing the odds of being accepted in a peer-reviewed journal? Also add a couple of “surprisingly” and “unexpectedly” to make it appear like a neo-Darwinian archaic pseudoscientific nonsense. Then it might be accepted right away. At least it should pass the peer reviews, because it will sound like music to their ears.””

    Sure. That could probably work! 🙂

  62. 62
    gpuccio says:

    Dionisio:

    “This is serious research you have presented here, as well as in the previous two OPs on related subject. I commend you for this effort. Thanks.”

    Thanks to you. 🙂

    When you BLAST the proteins SATB1 and SATB2 and analyze them, giving numbers that indicate relative positions within the proteins and their domains, what does that tell us about the actual DNA genetic information that was expressed into the given proteins?

    If the aminoacid sequence is conserved through hundred of millions of years, it means that it is under strong functional constraint.

    And if the aminoacid sequence is conserved in the protein, that means that the nucleotide sequence is conserved too in the corresponding gene, except for possible synonymous mutations.

    Where should one look to get a very simplified description of the DNA segments (containing introns + exons) that are transcribed into the corresponding mRNA molecules that are later translated by the ribosome machinery into the proteins SATB1 and SATB2? Basically, where in the DNA are the codons taken from? Is there an easy to understand map showing their relative locations within the DNA (i.e. chromosome number + relative position within the given chromosome)?

    There are many ways to get that information. The simplest way is probably the following:

    a) Go to the Uniprot page: http://www.uniprot.org/

    b) Search SATB1

    c) In the SATB1 page, scroll down till you find the Sequences section. After the protein sequence itself, there are other subsections. One of them is “Genome annotation databases”. Click on the link corresponding to the GeneID number

    d) You should be brought the the SATB1 gene page at NCBI. Here you can see that the SATB1 gene is located in chromosome 3, at the location 3p24.3, and that it includes 17 exons.

    e) Now, click on the link “Genome data viewer”. If you are lucky (at this precise moment it does not work for me! 🙂 ) you should be brought to a detailed graphical view of the pertinent genome segment.

    f) Another alternative (which at present is working) is to click on the link “Map viewer”, which bring you at a different form of graphic representations, where you can see the exons and the transcripts.

    I hope that helps.

  63. 63
    gpuccio says:

    Dionisio:

    By the way, SATB2 is on chromosome 2, at location 2q33.1, and it includes 16 exons.

  64. 64
    gpuccio says:

    Dionisio:

    “So how is this explained in the biology textbooks?”

    I don’t think it is explained.

    “Do they say it happened through the so called co-option or something like that?”

    I can think of a few different imaginative stories they could use, if asked. 🙂

    “Do they leave it as a temporary knowledge gap to be filled later when technology improves and science can get better information on how things could happen?”

    More likely, it’s no problem at all, for them.

    “Do they ignore it or skip over it as if nothing important happened?”

    Something like that, I suppose. Of course, I am not speaking of the specific issue that I have raised here in my OP about these two specific proteins, an issue of which only the lucky readers of this thread are probably aware! 🙂

    But of all the thousands of similar issues that can be found in the proteome, if one really wants to look at them.

  65. 65
    gpuccio says:

    Dionisio:

    “Isn’t it ironic that the whining politely dissenting interlocutors don’t join this discussion to present their strong arguments?”

    This is a free world.

    “Their absence is suspicious, isn’t it?”

    This is a free world.

    “Don’t they like serious scientific discussions?”

    This is a free world.

    “Can it get more serious and scientific than this?”

    It certainly can. But I am satisfied of the scientific context in my OPs.

    “Right now their nonsense comments are seen in other threads.”

    It is a free world.

    I am not joking: the same freedom that allows me to post my ideas here, certainly allows them not to comment on my ideas.

    OK, maybe I feel a little lonely at times, but I certainly do appreciate our quiet, intimate conversations here! 🙂

  66. 66
    Dionisio says:

    gpuccio @63:
    Thank you!

  67. 67
    Dionisio says:

    gpuccio @62:

    If the aminoacid sequence is conserved through hundred of millions of years, it means that it is under strong functional constraint.

    And if the aminoacid sequence is conserved in the protein, that means that the nucleotide sequence is conserved too in the corresponding gene, except for possible synonymous mutations.

    Thanks!

  68. 68
    Dionisio says:

    gpuccio @65:
    Yes, you’re right, it’s a free world. 🙂

    Well, at least one person showed enough interest to debate your ideas. RodW should be back with his strong counterarguments anytime soon, as he promised @21.
    I can’t wait to see the continuation of your interesting discussion with RodW.
    🙂

  69. 69
    Dionisio says:

    gpuccio @62:

    There are many ways to get that information. The simplest way is probably the following:

    a) Go to the Uniprot page: http://www.uniprot.org/

    b) Search SATB1

    c) In the SATB1 page, scroll down till you find the Sequences section. After the protein sequence itself, there are other subsections. One of them is “Genome annotation databases”. Click on the link corresponding to the GeneID number

    d) You should be brought to the SATB1 gene page at NCBI. Here you can see that the SATB1 gene is located in chromosome 3, at the location 3p24.3, and that it includes 17 exons.

    e) Now, click on the link “Genome data viewer”. If you are lucky (at this precise moment it does not work for me! ) you should be brought to a detailed graphical view of the pertinent genome segment.

    f) Another alternative (which at present is working) is to click on the link “Map viewer”, which bring you at a different form of graphic representations, where you can see the exons and the transcripts.

    I hope that helps.

    Yes, that helps much! Thank you.

    Thank you for providing the loci for SATB1 and SATB2 and for commenting on that particular subject too, providing detailed step-by-step instructions to find that kind of information.
    I should have searched for that information myself, but got used to ask the teacher instead. You have spoiled us here. We ask you easy technical questions instead of searching for the answers ourselves. That’s laziness, isn’t it? 🙂

  70. 70
    Dionisio says:

    To whom this may concern:

    Here’s some basic information –provided by gpuccio– about the genes that express the two important regulatory proteins discussed by gpuccio in this interesting thread:

    SATB1 gene is in chromosome 3, at the location 3p24.3, and it includes 17 exons.

    SATB2 gene is in chromosome 2, at the location 2q33.1, and it includes 16 exons.

    BTW,

    p stands for the short (petit) arm and q for the long (queue) arm.

    The digits that follow represent the region, band and sub-band respectively.

  71. 71
    Dionisio says:

    gpuccio,

    I followed your detailed instructions and the click on the link “Genome data viewer” did work for me. Thanks!

    Now I know how to find that information easily!

    Next time I visit Italy we’ll take you out for dinner. Just let me know your favorite local restaurant. Both my wife and I like Italian food. My children too. Still don’t know if my grandchildren will like it though. But anyway, who doesn’t like it? 🙂

  72. 72
    gpuccio says:

    Dionisio:

    And Sicilian food is fine, I would say. 🙂

  73. 73
    Dionisio says:

    these are fine:

    Arancine, Caponata, Sfincione, Panella, Maccu, Crocché, Fritedda (fritella), Pane con milza, Stigghiola, Ricotta Salata, Caciocavallo, Canestrato, Tuma, Primo Sale, Gattò, triglie, pesce spade, cipollata, Seppia, finnochio con sarde, Ricci, Beccafico, vitello alla marsala, Spiedini, involtini, Cannoli, Cassata, Frutta di Martorana (pasta reale),
    gelato, pistachio, nocciola, gelsomino, gelsi, fragala, zuppa inglese, Granita, Gelo di melone, Cuccìa

  74. 74
    gpuccio says:

    Dionisio:

    You are a true expert! 🙂

  75. 75
    RodW says:

    gpuccio

    Sorry for the delay. I’ll try to answer as many of your points as possible. I have a feeling this thread is dead so if you want to continue on a new thread let me know

    #10 CUT and HOX are also found in drosophila so even though the proteins are unique to vertebrates their parts are not.

    #11 There are new domains in vertebrates, but again, to continue on a common theme those domains are in turn made of combinations of secondary structure that are found in all proteins in all living things.

    I don’t think proteins are made of “fixed modules” and there are certainly functional sequences in some proteins between modules. But with all the massive sequencing and computing power I think most domains have probably been discovered. Still, I think its generally true that most of the functionality comes from the modules.

    The larger point I didn’t make in the last post is this: IDers try to make their case by highlighting the extreme improbably of generating function by natural processes. But when one looks at how proteins are put together and how function arises we can see that function could be generated by natural genetic mechanism and whats more theres abundant evidence for it. God could have done it any of a thousand ways so why he chose to do it exactly the way evolution would do it requires an explanation.

    Of course the homology, even if already high in sharks, continues to increase afterwards, up to the 100% or similar in primates. That is not difficult at all to explain, from an ID point of view.

    I’m not sure why you say this because you accept common descent. I got the impression from what you said in #13 that you’d agree that God created the sequences in an ancestral vertebrate and the differences in shark and human now are due to drift. I disagree that an IDer who doesn’t accept CD could explain it. Of course they’d have an explanation, but that explanation would fail on inspection.

    OK, well let me know where/if you want to continue. I purposely didn’t expand on some of the ideas because I thought we could get to that later.

  76. 76
    Dionisio says:

    RodW @75:

    I have a feeling this thread is dead […]

    Why do you have such a feeling? What makes you thing that way?

    Thanks.

  77. 77
    Dionisio says:

    RodW @75,

    Since you have been the only politely dissenting interlocutor who dared debating with gpuccio, but last week you had to pause until this week, the discussion here turned into a more intimate chat between friends., while waiting for you or someone else to heat up the room.

    Let me tell you that in my professional experience, had my former employer had the computers, the best programmers, all the office conditions and resources, but not the brilliant mind of my project leader who came up with the idea of the product and directed its development, testing, debugging, implementation, delivery and technical support, most probably it wouldn’t have been the successful product that it was, which allowed many engineers to do their design work more productively and accurately. The product existed in my project leader’s mind long before it was written in the tech and programming specs that my fellow programmers and I followed in order to develop the software.

    All the computers, programmers, and the whole nine yards together wouldn’t have produced such a successful software product in a million years, no matter how hard they would have tried.
    And note that I’m talking computers, programmers and all the required resources being available. We could have come up with many nice programs, maybe a few cool games, but not the serious engineering design software that was produced based on the ideas that were initially in my project leader’s mind and his marching orders to the rest of us.
    Ideas were first, implementation was next.

    The same is seen in biology these days, thanks to the tremendous technological advance that is allowing researchers to peek deeper into the biological systems, thus discovering elaborate molecular and cellular choreographies orchestrated in amazing shows that keep surprising the most dedicated scientists, who constantly see unexpected things and scratch their heads trying to figure out what next.
    Let’s stop fooling ourselves with all that barrage of Darwinian nonsense we hear around. The gross extrapolation of the embedded variability framework associated with the biological systems has inflicted an enormous damage to science for over a century. It’s time to trash all that and move on to cleaner science.

    BTW, Many times the anti-God folks are the first who mention Him. It’s their hatred that betrays them. Let’s keep God out of the scientific discussions, but let’s talk rigorous science, very technical, the whole enchilada.
    I want to love God with all my heart, my mind, my strength, He’s above science and everything else. He made everything that is. He’s the root of the true ultimate reality. That’s it. beginning and end. Alpha and Omega. All in all.
    But for the sake of clarity I don’t have to mention Him in the purely scientific discussions.
    But then let’s roll up our sleeves and get to serious discussions. It ain’t gonna be easy, but we can try.

    We ain’t seen nothin’ yet.
    The most fascinating discoveries are still ahead.
    The ride has just started. Let’s fasten our seatbelts.

  78. 78
    gpuccio says:

    RodW:

    Glad to hear from you again! 🙂

    I think we can continue our discussion here. No thread is really dead until there are people who want to discuss.

    I will try to address your points in order, starting with next post. In the meantime, if you like, you can look at some interesting exchanges between Dionisio and me, for example about Sicilian cuisine! 🙂

    You could also, always if you like, look at my post #55 here, which adds some detail to one of the points I have tried to make.

    And now, let’s start the discussion.

  79. 79
    Dionisio says:

    RodW @75,

    I invite you to join us for dinner next time I visit Sicilia. gpuccio will let us know his restaurant preferences, but I already indicated @73 my “limited” list of acceptable items that should be in the menu –approved by gpuccio. My only additional request is that the restaurant is located by the littoral, and the table outside, under a large umbrella. 🙂
    Another caveat: if my wife joins us too, then the conversation should not include any scientific topics, because she does not care much about our boring nerdy issues. Therefore we should use the opportunity to let gpuccio describe the beautiful views of the sea and the mountains and the surroundings, along with the history of the city. That should make her happy! 🙂

    just FYI – please, be aware of the fact that you’re on the side of the debate that is doomed to become a shamefully stained page in science history. You’ll do yourself a favor if you realize that sooner. Many folks here can help you understand this. Most probably gpuccio is willing to answer any questions you have, considering that “I don’t know” is a valid answer too. I don’t expect gpuccio to embarrass himself by claiming to know something that he knows that he does not know. A Canadian professor made that embarrassing mistake here a couple of years ago, but still some politely dissenting interlocutors here keep basing their nonsense commentaries on the opinion of that professor.
    Let’s hope you can do better than that. Thanks.

  80. 80
    gpuccio says:

    RodW:

    OK, let’s try to deepen our discussion about domains.

    Just as a start, I would like to say that, even if my recent analysis has not focused in particular on daomains, it is absolutely true that domains were one of my forst arguments in discussing ID.

    Indeed, one of the best arguments for ID remains the existence of about 2000 domain superfamilies (referring to SCOP, release 1.75, we have 1195 different folds, 1962 superfamilies, 3902 families).

    As superfamilies are by definition groups for which no evolutionary relationship can be shown, neither at the level of structure nor at the level of sequence, the simple fact remains that we have to explain how about 200 functional superfamilies of protein domains came into existence, each of them with specific functions, each of them and isolated island of functionality in the ocean of sequence space.

    There is no possible neo darwinian explanation for that.

    One of the first examples I used was ATP syntase, alpha and beta chains. For example, the alpha chain is 553 AAs long, and the human sequence shows 561 bits of homology with the protein in E. coli, 290 identities, 373 positives.

    This homology has survived for… what? 3-4 billion years?

    I have asked to all neo darwinists who have posted here: how do you explain that? What possible pathway can you show for this highly optimized protein domain, existing practically at the beginning of life on our planet, which is part of a much more complex and sophisticated molecular machine?

    Nobody has ever even tried to offer an answer.

    But you say:

    “But when one looks at how proteins are put together and how function arises we can see that function could be generated by natural genetic mechanism and whats more there’s abundant evidence for it.”

    And I ask: what evidence? I am aware of no evidence at all that “natural genetic mechanism” can generate any amount of specific functional information above a few bits, certainly not above 120 bits (which is the threshold that I have proposed as a biological probability bound), even less above 500 bits (Dembski’s Universal Probability Bound, computed for the whole universe as a whole machine).

    Now, I will call you to reference your statement. What is the abundant evidence?

    In particular, if you can, could you suggest how “natural genetic mechanisms” could generate the following?

    a) 561 bits of functional information in ATP synthase alpha chain (conserved for billions of years)

    b) 663 bits of functional information in ATP synthase beta chain (conserved for billions of years)

    c) 1545 bits of functional information in the system SATB1 – SATB2 (conserved for more than 400 million years): see my OP here

    d) More than 1.7 million bits of functional information in the transition from non vertebrate chordates to the first vertebrates (conserved for more than 400 million yeras). See my previous OP:

    https://uncommondescent.com/intelligent-design/the-amazing-level-of-engineering-in-the-transition-to-the-vertebrate-proteome-a-global-analysis/

    OK, this for a start. More in next post.

  81. 81
    gpuccio says:

    RodW:

    More about domains.

    You say:

    “CUT and HOX are also found in drosophila so even though the proteins are unique to vertebrates their parts are not.”

    But I have blasted SATB1 (human) against drosophila melanogaster (all sequences), and the result is:

    62.4 bits of maximum homology, with protein Dve.

    The only local alignment includes 186 AAs, segment 74 – 240 of the human sequence, with 47 identities and 92 positives. As you can see, this homology (very partial) refers to the first two domains (SATB1N and CUTL) as shown in the Blast figure, and not to the two CUT domains or to the HOX domain, where no homology can be detected.

    Now, let’s look to the segment that, in the Blast Figure, is marked as HOX domain. It corresponds to AAs 644 – 701, and Blast gives a low homology of that sequence to the reference HOX domain (Expect 2.38e-08).

    Now, if we blst that specific sequence of 58 AAs vs drosophila, the best hit is:

    Chain A, Even-Skipped Homeodomain Complexed To At-Rich Dna

    28.1 bits Expect 0.17 12 identities 17 positives, in a partial alignment of only 20 AAs.

    Here it is:

    Query 678 LSAQLDLPKYTIIKFFQNQR 697
    L+AQL+LP+ TI +FQN+R
    Sbjct 34 LAAQLNLPESTIKVWFQNRR 53

    While, if we blast the same “domain” (segment) with cartilaginous fish, we have:

    114 bits Expect 1e-31 55 identities 56 positives

    and an alignment if all the 58 AAs in the segment.

    Here it is:

    Query 644 KTRPRTKISVEALGILQSFIQDVGLYPDE
    K R RTKISVEALGILQSFIQDVGLYPDE
    Sbjct 550 KPRSRTKISVEALGILQSFIQDVGLYPDE

    EAIQTLSAQLDLPKYTIIKFFQNQRYYLK 701
    EAIQTLSAQLDLPKYTIIKFFQNQRY+LK
    EAIQTLSAQLDLPKYTIIKFFQNQRYHLK 607

    This is the domain as it appears in this specific protein, and is conserved in vertebrates throughout 400 million years. As you can see, it has only a vague resemblance, not even significant, with the domain we find in drosophila (Expect 0.17).

    Are you really sure that we are discussing the same thing?

    Don’t you suspect that there is a lot of specific functional information in the vertebrate domain which is not present before the appearance of vertebrates?

    How do you believe that specific sequences, which are so optimized that they are conserved after they appear, are found by RV? And without any trace of empirical evidence of any possible selectable pathway, and no trace at all of intermediate forms?

    My question is very simple: these highly specific sequences appear for the first time in cartilaginous fish. And they are conserved throughout the human lineage.

    Of course they arise at some time in the last common ancestor of vertebrates. How? When? With what mechanism?

    We are discussing thousands of functional bits, millions if you consider the whole vertebrate plan.

    What do you say?

  82. 82
    gpuccio says:

    RodW:

    I should discuss the aspect of Common Descent now, I suppose. But dinner awaits me (and a wife!). More in next post, as soon as possible! 🙂

  83. 83
    RodW says:

    Dionisio

    Yes, I realize gpuccio is from Italy. Americans who visit Europe and some Italians I know all insist the food is much better in Europe and especially Italy. I’m willing to believe that but I don’t know why that should be the case. Can’t we produce good food in the US?? Sometimes I think they’re just so happy to be in Italy they imagine the food is better. Some have even said the Nutella is better in Italy but that cant be the case

  84. 84
    gpuccio says:

    RodW:

    Nutella is probably the same. But what about pasta? 🙂

  85. 85
    gpuccio says:

    RodW:

    Now, let’s be serious again.

    You say:

    I don’t think proteins are made of “fixed modules” and there are certainly functional sequences in some proteins between modules. But with all the massive sequencing and computing power I think most domains have probably been discovered.

    Not necessarily. The identification of a domain usually requires studies of the structure, which at present are still difficult.

    However, two important points that I mentioned are:

    a) Very similar structures can certainly behave differently, if there are differences, even slight ones, in the sequence and in the general context of the whole molecule. That’s why multidomain proteins are never simply a collection of domains, even when the domains are similar enough (that, as we have seen, is not always the case, at all). The domains must interact in specific ways, and it is the general architecture of the proteins that ensures that.

    b) Much protein function is not rigidly tied to a fixed structure. It’s the case of intrinsically disordered proteins, which have become a very important part of our understanding of protein function. I quote from Wikipedia:

    “An intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure.[2][3][4] IDPs cover a spectrum of states from fully unstructured to partially structured and include random coils, (pre-)molten globules, and large multi-domain proteins connected by flexible linkers. They constitute one of the main types of protein (alongside globular, fibrous and membrane proteins).[5]

    The discovery of IDPs has challenged the traditional protein structure paradigm, that protein function depends on a fixed three-dimensional structure. This dogma has been challenged over the last decades by increasing evidence from various branches of structural biology, suggesting that protein dynamics may be highly relevant for such systems. Despite their lack of stable structure, IDPs are a very large and functionally important class of proteins. In some cases, IDPs can adopt a fixed three-dimensional structure after binding to other macromolecules. Overall, IDPs are different from structured proteins in many ways and tend to have distinct properties in terms of function, structure, sequence, interactions, evolution and regulation.”

    Then you say:

    Still, I think its generally true that most of the functionality comes from the modules.

    Maybe, but as I have said that is questionable. And, in any case, the “modules” are not fixed and can be modified in thousands of ways for each functional requirement. And all that means functional information.

    And, in the end, the important point is: there is only one place where that functional information can and must be found: the sequence

    Why?

    Because it’s the sequence, the primary structure, which in the end generates all the rest. The sequence is written in the mass memory (protein coding genes), and it’s in the sequence space that variation happens.

    Mutations, be they random or guided, happen in the sequence of the protein coding gene, and therefore they are variations in the sequence space. Especially random variations, which are the only engine in the neo-darwinian paradigm, know nothing of secondary and tertiary structure, least of all of function. Random variation is by definition blind, therefore it is just a “movement” in the sequence space. Nothing else.

    It’s in the sequence space that the search is done, whatever the search is. And the sequence space dictates the probability context, if the movements is random. And we know all too well how big and disconnected is the sequence space of proteins: let’s say 20^100 different states for a “short” 100 AAs protein sequence?

    It’s 432 bits of total information for that short sequence. And, already, it’s an ocean that no RV can traverse.

    Again, I call for some explanation of the following facts:

    a) 561 functional in ATP synthase alpha chain (conserved for billions of years)

    b) 663 functional bits in ATP synthase beta chain (conserved for billions of years)

    c) 1545 functional bits in the system SATB1 – SATB2 (conserved for more than 400 million years): see my OP here

    d) More than 1.7 million functional bits in the transition from non vertebrate chordates to the first vertebrates (conserved for more than 400 million years). see my previous OP.

    More in next post.

  86. 86
    gpuccio says:

    RodW:

    You say:

    God could have done it any of a thousand ways so why he chose to do it exactly the way evolution would do it requires an explanation.

    Ah, this is strange indeed.

    A) Whoever spoke of God?

    Let’s be clear, I am not trying to hide behind tricks. I really am not speaking of God here.

    I have never, never invokes any religious idea when I am discussing ID. ID for me is science. Period.

    Then, what are we speaking of? We are speaking of the necessity of one or more designers to explain the generation of functional information in biology and its natural history.

    We are speaking of the simple fact that complex functional information never, never originates without the intervention of some conscious designer capable og the specific conscious representations of meaning and purpose. Only those conscious representations can overcome the probabilistic barriers that make the generation of complex functional information practically impossible in all non design contexts.

    Is that designer or designers God?

    My answer is: what do observed facts tell us? Only that conscious and purposeful intelligence is required. Is that enough to say it was God?

    No. Not from a scientific point of you. The only requirement is conscious purposeful intelligence, and the ability to interact with biological beings in order to input some specific form to their stored information.

    So, we don’t know why and how the designer designed biological information, and certainly we cannot try to derive that from some a priori concept of God. As you seem to do.

    But I have never done that.

    So, let’s try to see what the facts have to tell us.

    The facts tell us that information in natural history grows suddenly, in big jumps. Of course the first, and most relevant, jump is OOL, but unfortunately we know really little about that.

    But I have tried to show, with my last OPs that some definite information jumps can be very well identified in more “recent” natural history, for example in the transition to vertebrates. And I have tried to quantify those jumps, and to support my conclusions as empirically as I could.

    I am still waiting for real objections to my procedure and conclusions.

    More in next post.

  87. 87
    Dionisio says:

    RodW @83,

    sometimes I feel Italian too 🙂

    Except that my Italian vocabulary is very poor compared to gpuccio’s 🙂

    the best food is the Sicilian! 🙂
    [see it @73]

    the worst was in the archipelago Gulag 🙁

    regularly I eat Polish or Spanish food, but like any cuisine, as long as it’s affordable 🙂

    Now, seriously, the best biochemical food is the one we can share!

    But of course, it must provide the essential nutrients required by our bodies to function, so our souls can operate in this world.

    OK, enough digression, time to focus in the discussion.

  88. 88
    Dionisio says:

    gpuccio @80:

    Indeed, one of the best arguments for ID remains the existence of about 2000 domain superfamilies (referring to SCOP, release 1.75, we have 1195 different folds, 1962 superfamilies, 3902 families).

    interesting information

  89. 89
    gpuccio says:

    RodW:

    Another thing that facts tell us is that the input of new functional information takes place in already existing beings, in some way.

    That’s what I mean with “Common descent”, and more in particular with “Designed Common Descent”.

    It’s not different from what happens in human design, for example in design of cars or of software.

    Designers who work on a new model of car, often reuse some old model and just modify it as desired.

    Of course, that is not always the case, but let’s imagine a world where the only practical way to make a new car is to take an old one and modify it. That would generate an Universal Common Descent of cars, and yet each single new car would be designed. That would also generate naturally a nested hierarchy of designed cars.

    Now, I really don’t know if CD is universal or not. I only know that some form of CD is apparently neede to explain many important observed facts. That’s why I believe in CD. Again, it’s not form of religion or anti-religion: it’s just my scientific conviction.

    And, of course, it makes sense only with design. Because “natural” CD (non designed CD), without any design intervention, can never explain functional information.

    B) So, why do you say that:

    “why he chose to do it exactly the way evolution would do it requires an explanation”

    But facts are exactly the opposite of “the way evolution would do it”.

    The way evolution (neo-darwinian evolution) would do it is what we could call “Dawkins’dream”: a natural history full of gradual modifications, each of them slightly more functional, each of them naturally selected and amplified and fixed, so that we can at least find traces of it, and clear pathways of gradual increases of functionality.

    The opposite of what we can observe.

    The way evolution would do it would provide lots and lots of empirical examples of how really new original functional information can arise thorugh RV + NS: in natural history, in the lab, even in software. Insted, we have none. Absolutely none. (OK, now you will quote the usual mystifications, like Szostak’s paper, or evolutionary softwares, and so on. I have debated those things hundreds of times, and I am a little tired of doing that. But you are a new person, and therefore, if you want to do that, let it be).

    So, observed facts tell us that whatever happened, it’s not “the way evolution would do it”. It’s the way one or more designers, constrained by context, not necessarily omnipotent, and constrained by some necessity, or opportunity, to operate through some Common Descent, more or less universal, would do it.

    Is that clear? Natural history is not the way evolution would do it. It’s the way designers would do it. That’s what is meant when we say that biological beings have, strongly, the appearance of design, something that even die hard evolutionists like Dawkins admit.

    Otherwise, we would simply say that biological beings have the appearance of neo-darwinian evolution (whatever that can mean).

    So, what is at stack here is not what some imaginary idea of God would have done. We must ask ourselves what a designer would have done, given specific constraints. Exactly as happens in human design.

    More in next post.

  90. 90
    RodW says:

    gpuccio

    I don’t have time to do research now so I’ll go from memory, but this discussion is a good excuse to look up some papers on the topic

    I am aware of no evidence at all that “natural genetic mechanism” can generate any amount of specific functional information above a few bits,

    The mechanisms are inversions, translocation, deletions and insertions. They could be caused by random breaks, TEs and meiotic slippage during pairing. There is a new protein in drosophical (I think its called jumanji) created by the fusion of parts of 2 other proteins. When you look at protein families some of the proteins will be almost identical, others will differ in the regions between the domains and still others will add or delete a domain or 2.

    and not to the two CUT domains or to the HOX domain, where no homology can be detected.

    The CUT domain was first found in the cut protein in drosophila, so named because it made the wing margin look ‘cut’. And of course the hox genes were discovered first in drosophia. They were responsible for the famous homeotic transformation mutants. Didn’t you see the 4-wing fly picture that Wells used in Icons of Evolution? The genes were found in mouse when G Rubin at UCLA probed a mouse library with the fly gene. You might be interested to know that if you put the homologous (equivalent) mouse gene into the fly mutant it corrects the mistake. (I think the reverse experiment works sometimes)

    As for domains

    Indeed, one of the best arguments for ID remains the existence of about 2000 domain superfamilies (referring to SCOP, release 1.75, we have 1195 different folds, 1962 superfamilies, 3902 families)………
    There is no possible neo darwinian explanation for that.

    I disagree. When one looks closely at domains most are composed of a few bits of secondary structure and function by binding specifically to some molecule. You may be aware that its very easy to generate a random series of proteins, or even short polypeptides, and find the ability to bind to something specific. So the big complex proteins we see today could easily have arisen by cobbling together simpler elements that predated LUCA. One researcher (Tawflik I think) did an analysis of several domains and found that they appear to have been generated from modification from much simpler repeat sequences of aa. Its know that very simple repeat polypeptides..ex. Glu-Pro-Glu-Pro etc can have a function. What all this means is that even though we don’t have a detailed picture for how these came about we can still see that an ID isnt required. The picture we have now may be an outline, but it still suggests the gradual ratcheting up of complexity by natural mechanisms.

  91. 91
    RodW says:

    I’ve always thought books make bad presents. When you give someone a book you’re essentially saying “here, now spend ~50 hours of your free time reading this!”

    I’m going to go ahead and recommend 2 books to you guys. This is not the same thing because you all clearly put a lot of time and thought into this topic. The thing is it seems you get most of your info and interpretation through an ID community filter. I’m not saying this will persuade you that ID is wrong but you’ll see that outside of the ID community no one thinks that evolution is on the verge of collapse. Every day papers come out that interpret their results in terms of evolution. At the very least evolution is consistent with their results. In some cases ID isn’t.

    So the books you should read cover to cover are the latest editions of
    Molecular Biology of the Cell by Alberts
    Evolution by Futuyma

  92. 92
    gpuccio says:

    RodW:

    Now you say:

    I got the impression from what you said in #13 that you’d agree that God created the sequences in an ancestral vertebrate and the differences in shark and human now are due to drift.

    No, I will try to be more clear. And let’s get rid of the idea of God in this discussion.

    My point are:

    a) The sequences that are conserved throughout the 400+ million years must be considered functional sequences.

    b) Those that are shared between cartilaginous fish and humans, and were never observed in non vertebrates, including non vertebrate chordates, must have originated in the last common ancestor of vertebrates, and therefore in a rather short evolutionary time. For those sequences, if complex enough, I infer design, according to the most classic ID theory.

    c) Now, we have two molecules, SATB1 and SATB2. In humans, they share a relevant quote of sequence information (854 bits, 460 identities). In sharks, the two molecules share almost exactly the same sequence information (856 bits, 468 identities).

    d) The obvious conclusion is: the two molecules share about 855 bits of functional information, and that quote of functional information was already present in the last
    ancestor of vertebrates, and it has been conserved from then on.

    OK? Is it clear?

    e) But the two molecules have additional functional information that has been conserved for 400+ million years. Only, that information is different in the two molecules, but in each molecule it has been conserved for 400+ million years. That information must be related to the specific function that each molecule performs differently from what the other one does.

    f) I have quantified that specific information. Let’s consider 855 bits the information shared by the two molecules (the mean of 854 and 856).

    Then, for SATB1, the specific conserved information is:

    348 bits

    (1203, that is the total homology between human and shark SATB1, – 855)

    And for SATB2, the specific conserved information is:

    342 bits

    (1197, that is the total homology between human and shark SATB2, – 855)

    Remarkably similar, again.

    The point is, the 348 bits conserved in SATB! (beyond the shared 855 bits in the two molecules) are completely different from the 342 bits conserved in SATB2 ((beyond the shared 855 bits in the two molecules). They are completely different functional sequences, not shared bewteen the two molecules.

    That’s why I say that the whole functional information in the system is:

    855 + 348 + 342 = 1545 bits.

    However, if we consider that 154 bits were alredy detectable in pre-vertebrates, we can conclude that the total information jump in vertebrates for the two molecules is:

    1545 – 154 = 1391 bits.

    (By the way, I apologize for having written 1545 in my last comments, I had forgotten to subtract the 154 bits of the best pre-vertebrate hit. Not that it makes a big difference… 🙂 )

    g) What about the sequence that is not conserved between sharks and humans?

    As always, let’s be quantitative. As the maximun homology in blast results is about 2.2 bits per aminoacid (for total identity) we can say that the non conserved part is:

    About 476 bits for SATB1

    About 416 bits for SATB2

    Not too much, I would say.

    As you correctly say, this “gap” with the human sequence is, more or less gradually, filled in the course of the remaining natural history.

    That is rather obvious, After all, we must get to primates, which have almost complete sequence identity with humans.

    As you can see in Fig. 7, the gap is almost completely filled already in crocodiles, even more in mammals.

    What does that mean?

    I have tried to discuss it in post #13, and I invite you to read it again.

    In brief, I don’t think that “all” the sequence must have functional constraints. There can be neutral divergence, of course. In that case, only par of those remaining bits are functional, and can be traced to specific new functional adaptations of the molecule in the new species. The rest could be neutral or quasi-neutral. The almost complete homology in mammals, for example, can be explained in part by passive conservation of neutral sites, in a time window (100 million years or less) that cannot ensure saturation of neutral site divergence.

    But, with what we know, it is almost impossible to separate additional functional information from neutral conservation in the part of the molecule which is not conserved from sharks, or at least from bony fish.

  93. 93
    gpuccio says:

    RodW:

    Thank you for your contributions. It is late now here, so I will answer tomorrow.

    Good discussion, anyway! 🙂

  94. 94
    gpuccio says:

    RodW:

    By the way, to prepare some of my answers tomorrow, I would appreciate if you could give more precise references to the following things you mentioned:

    Tawflik

    jumanji

    Thanl you.

  95. 95
    Dionisio says:

    gpuccio @85:

    And, in the end, the important point is: there is only one place where that functional information can and must be found: the sequence
    Why?
    Because it’s the sequence, the primary structure, which in the end generates all the rest. The sequence is written in the mass memory (protein coding genes), and it’s in the sequence space that variation happens.

    It’s in the sequence space that the search is done, whatever the search is. And the sequence space dictates the probability context, if the movements is random.

    Interesting information.

    That’s one of the reasons I wanted to learn how to look at the genes that code for the proteins SATB1 and SATB2. You told me the tips and tricks. Thanks.

  96. 96
    Dionisio says:

    gpuccio @86:

    Whoever spoke of God?
    Let’s be clear, I am not trying to hide behind tricks. I really am not speaking of God here.
    I have never, never invokes any religious idea when I am discussing ID. ID for me is science. Period.

    Yes, RodW and other politely dissenting interlocutors should keep God out of the technical discussions. Sometimes it seems like they bring God into the discussion to detour it or to hide their lack of serious scientific arguments. To me mixing the two concepts the naïve way they do it is even disrespectful to God. I believe God is above and beyond everything that is. Science is a minuscule –actually insignificant– area in comparison. But for some of us it’s very interesting and important at this moment, and it’s overwhelmingly huge and has many unknowns we want to identify. Science presents difficult tasks before us. Let’s not digress. Let’s stick to the discussed subject.

    On this topic I wrote @77:

    BTW, Many times the anti-God folks are the first who mention Him. It’s their hatred that betrays them. Let’s keep God out of the scientific discussions, but let’s talk rigorous science, very technical, the whole enchilada.
    I want to love God with all my heart, my mind, my strength, He’s above science and everything else. He made everything that is. He’s the root of the true ultimate reality. That’s it. beginning and end. Alpha and Omega. All in all.
    But for the sake of clarity I don’t have to mention Him in the purely scientific discussions.
    But then let’s roll up our sleeves and get to serious discussions. It ain’t gonna be easy, but we can try.

    Everywhere I look around I hear people saying OMG for anything, no matter how insignificant it is. Most probably they careless about God. It’s just a filler, like “you know”, to cover a pause when the vocabulary is poor or when silent pauses are avoided, so that others don’t jump in and start talking.

    Let’s stick to technical and scientific terminology as rigorously as possible. Then we’ll understand things better.

    There’s much more to life beyond science, but when discussing science, let’s stick to it. Let’s not cross the boundaries around the scientific domain.

    Perhaps sometimes I mention God when the subject lacks seriousness because archaic pseudoscientific nonsense is presented as scientific facts. But in gpuccio’s OPs the technical level is pretty high, hence serious concentration is required to digest its content and discuss.

  97. 97
    Dionisio says:

    gpuccio @93:

    Yes, the discussion between RodW and you is very interesting.

    Thanks to both of you for keeping it going.

  98. 98
    Dionisio says:

    RodW @91:

    The thing is it seems you get most of your info and interpretation through an ID community filter.

    In my case you got it wrong.

    I get most of my biology-related information directly from peer-reviewed online journals that definitely are NOT ID-friendly. I may not like their reductionist bottom-up reverse-engineering approach to research, and definitely dislike the archaic pseudoscientific hogwash they insert in their text, but still I use those papers, because there is not much more out there to look at.
    Also, watched a few biology-related online courses from MIT and the Weizmann Institute. One on Development, and two on Systems Biology.
    My main activity in this website is sharing references to research papers I’ve gathered for a project I’m working on. Sometimes I write comments in some discussion threads.
    Next time make sure you verify the information you have before you say something publicly about it. It seems like your sources are not very reliable. 🙂

  99. 99
    Dionisio says:

    gpuccio @92:

    By the way, I apologize for having written 1545 in my last comments, I had forgotten to subtract the 154 bits of the best pre-vertebrate hit. Not that it makes a big difference…

    Thank you for publicly admitting that mistake and for quickly making the required correction. Such an honest act increases the credibility of the research work you do.
    Well done!

  100. 100
    RodW says:

    Gpuccio
    Correction. Jingwei not jumanji. And Dan Tawfik not tawflik. Look up his refs. Having trouble tracking down that paper

    Dionisio. Apologies but I think that applies to most people here

  101. 101
    DATCG says:

    Gpuccio, always interested to read what you post 🙂

    Look forward to the series.

    Enjoying the post, your commentary and responses. As well as RodW and Dionisio. I think each debated area brings out more information overload for Darwinist.

    I’ve read, skimmed over 15 different science publications on SATB1, SATB2 and Inter-domain, Inter-Domain linkers functionality, and coordination of multi-domain proteins so far. But time to call it a night.

    I became interested about inter-domain linkers.

    A quote from research for improved search efficiency of “inter-domain linkers” …

    Inter-domain linkers tie neighboring domains and support inter-domain communications in multi-domain proteins. They also provide sufficient flexibility to facilitate domain motions and regulate the inter-domain geometry [4].

    Recap, Inter-domain linkers:
    1) Tie neighboring domains
    2) support inter-domain communications across multi-domain proteins
    3) Facilitate domain motions
    4) regulate inter-domain geometry

    Besides the question, how do Linkers arise thru Blind RV over time, I thought after your discussion and reading, okay, how might they vary? And here’s another quote from a different paper: Structural properties of the linkers connecting…

    3.4. Sequence similarity
    Linker sequences were used as queries in a BLAST search against the entire RefSeq protein databank to verify the presence of significant similarity to any other protein segments. Results suggest that linker sequences are hypervariable: we detected indeed only similarities between MocR linkers from organisms related at the level of species or genus. Only in a few cases, significant similarities were found between MocR linkers from different bacteria phyla (an example is reported in Fig. 5).

    This example was from bacteria. Do you find this interesting in relation to your comments above on inter-domain?

    Ran a BLAST query against Zebra Fish. Showed a 76% Identity.

    Look forward to more reading tomorrow and rest of series.

  102. 102
    DATCG says:

    Gpuccio, or UCD writers,
    Off-subject… maybe another post or Series after this one on Haldane’s Dilemma, Kimura – Neutral Theory and JUNK DNA?

    JohnnyB’s post, including Sal’s videos(1 & 2) with interesting insight to Graur’s rant against ENCODE I think sheds more light on fallacy of so much “JUNK” DNA.

    Plus, how the different functions, markers, enchancers, silences, linkers, etc., all combine and coordinate appears to overwhelm any blind, unguided variation, even with neutral model.

    Since there are differing opinions in ID community on Neutral model, might be a good subject with interesting insights.

  103. 103
    gpuccio says:

    DATCG:

    Thank you for your very interesting contributions.

    Interesting paper about MocR linkers in bacteria.

    I became aware of the extreme conservation of some interdomain sequences when I worked at my two OPs about Prickle proteins:

    https://uncommondescent.com/intelligent-design/homologies-differences-and-information-jumps/

    and

    https://uncommondescent.com/intelligent-design/information-jumps-again-some-more-facts-and-thoughts-about-prickle-1-and-taxonomically-restricted-genes/

    where I found that the non domain part of those regulatory proteins was the one that presented a high information jump in vertebrates.

    The results presented here about SATB1 and SATB2 are very interesting, too.

    Regulatory proteins seem to have, quite often, long non domain sequences.

    For example, ATM, an important human protein 3056 AA long, has an interdomain sequence which is 1930 AAs long!

    This protein has a significant vertebrate jump (although less prominent than in the SATB couple) of about 0.6 bits per aminoacid site.

    However, that interdomain sequence shows 2152 bits of homology between humans and sharks (callorhincus milii), with 1091 identities!

    Isn’t that a strong signature of functionality?

    I find very useful blasting segments: that gives an immediate idea of the conservation of different parts of the molecule, which could not be obvious when we look at the whole molecule blast.

    Regarding neutral variation, I absolutely believe that it has an important part in natural history. Indeed, my reasonings are based exactly on the concept of neutral variation: it’s the absence of neutral divergence where it should be found that represents my basici metrics for functional information.

    But I will say something more about that in my answers to RodW! 🙂

  104. 104
    Dionisio says:

    RodW @100:

    “Apologies but I think that applies to most people here”

    Huh? What’s “that” ?
    Can you quote the text your statement relates to?
    Also, please indicate the post # where the quoted text was copied from.
    Thanks.

  105. 105
    gpuccio says:

    RodW:

    Before going in more details about your comments, I would like to say a couple of general things:

    a) the main argument in my OP and in the following comments is about the sudden appearance of complex sequences in vertebrates, that are then conserved up to humans. I consider such conservation as a signature of functionality, and I infer design because no neo darwinian process could build such a huge amount of functional information in such a short evolutionary time, and without leaving any trace of its imagined pathways.

    The simple fact is: you have made no specific comment about these points. I would really like to know what you think of the conservation issue, and its relationship to functionality.

    b) You say:

    The thing is it seems you get most of your info and interpretation through an ID community filter.

    Well, I absolutely agree, except for the word “community”. The statement should be rephrased, IMO, as follows:

    “The thing is it seems you get most of your info and interpretation through an ID filter.”

    I derive my info from the scientific literature (and, of course, from my personal scientific background), but I certainly build my interpretations, when appropriate, through an ID filter. And I am very happy to do that!

    Why? Because I have chosen ID as my paradigm for the interpretation of biology, and I have done that with full understanding of its meaning and import, and with full awareness of what I was doing.

    I can certainly say that it is equally true that most researchers and scientists get most of their info and interpretation through a neo-darwinian (community) filter.

    Each person has the privilege and duty to filter reality, and science, through the cognitive paradigms he has chosen.

    Finally, you say:

    you’ll see that outside of the ID community no one thinks that evolution is on the verge of collapse.

    Believe me, we are not completely stupid. We know that all too well.

    I have chosen ID with the absolute awareness that it was a super-minority choice. But I am convinced of it, and I try to share with others the reasons why.

    In my conscience, the neo-darwinian paradigm has already collapsed. It has really no credibility for me.

    The more I know about scientific advances in biology (and other fields), the more I am convinced of it.

    But of course, it has not collapsed in the general consensus. The cognitive bias that has established itself in our culture has such a dogmatic grip, that frankly I don’t know how long it will take for that collapse to come. But it will come, I am certain of that.

    But if you ask if I am aware that almost everybody thinks differently, then the answer is simple enough: yes, I am well aware of that.

    In next posts, I will try to address some of the issues that you have commented upon.

  106. 106
    gpuccio says:

    RodW at #90:

    Now, let’s go to the specifics of what you say.

    The statement of mine that you quote is the following:

    “I am aware of no evidence at all that “natural genetic mechanism” can generate any amount of specific functional information above a few bits,”

    I have emphasized here the important concept. As you can see, I always reason in terms of functional complexity, and I try to quantify it. Any other approach makes no sense from the point of view of ID.

    For my definitions of functional information, you can look at this old OP of mine:

    https://uncommondescent.com/intelligent-design/functional-information-defined/

    OK, let’s take for granted that you know what I mean (we can always go back to that, if necessary).

    In this OP, like in those that preceded it, I use a specific metrics to measure functional information, or at least part of it, in proteins. I have already explained what you do, so I will not repeat myself for the moment.

    That’s why it would be important that you gave some feedback on the points I have listed at my post #105, a). If I don’t know what you think of my metrics, and why, it can be difficult to discuss in depth.

    After quoting my statement, you say:

    The mechanisms are inversions, translocation, deletions and insertions. They could be caused by random breaks, TEs and meiotic slippage during pairing.

    Now, let’s be clear: all the “mechanisms” you mention can be briefly described as forms of Random Variation (form now on, RV). So, you are saying that RV is the mechanism
    that “can generate amounts of specific functional information above a few bits”.

    It’s strange that you don’t mention Natural Selection here, but OK, we will certainly come back to that in the discussion.

    So, you believe that RV (+NS) can generate complex functional information. OK, you are entitled to that. But where is the evidence?

    I have already stated that I am not aware of any of it.

    Well, my statement was in response to this statement of yours:

    IDers try to make their case by highlighting the extreme improbably of generating function by natural processes. But when one looks at how proteins are put together and how function arises we can see that function could be generated by natural genetic mechanism and whats more theres abundant evidence for it.

    I think we must clarify an important issue here. You cannot use the word “function”. You must use “new original complex functional information”.

    Function is not good. It is not something that can be quantified. Functional information (the information in bits necessary to implement a function) is the real thing. ID infers design from complex functional information, not from function.

    Are we OK about that? It’s very important.

    So, I will take your statement as though it were:

    “But when one looks at how proteins are put together and how new complex functional information arises we can see that new complex functional information could be generated by natural genetic mechanism and whats more there’s abundant evidence for it

    (emphasis mine)

    Otherwise, your statement makes no sense from the point of view of ID. ID is not a theory of function. It is a theory of complex functional information as the signature of detectable design.

    Now, what is the “abundant evidence” that you are offering, and of which I was not aware?

    It’s not so clear, but I will try to interpret what you say.

    And I will start from your conclusive statement:

    Its know that very simple repeat polypeptides..ex. Glu-Pro-Glu-Pro etc can have a function.. What all this means is that even though we don’t have a detailed picture for how these came about we can still see that an ID isnt required. The picture we have now may be an outline, but it still suggests the gradual ratcheting up of complexity by natural mechanisms.

    (emphasis mine)

    So much for the “abundant evidence” (in your own words)!

    And still, it seems that you are talking of “function”, not of complex functional information, thereby completely missing the point of ID theory, even if the word “complexity” finally comes out at the end of your statement, smartly coupled to the concept of “gradual ratcheting up”. Maybe NS is coming out, in the end!

    More in next post.

  107. 107
    gpuccio says:

    RodW at #90:

    You say:

    There is a new protein in drosophical (I think its called jumanji) created by the fusion of parts of 2 other proteins. When you look at protein families some of the proteins will be almost identical, others will differ in the regions between the domains and still others will add or delete a domain or 2.

    You then clarified at #100 that the protein’s name is Jingwei, not jumanji.

    I am not sure of your point here, it seems to be that exon shuffling, or other forms of remixing of existing information do take place in natural history.

    But I obviously agree on that. To decide if those events are easily explained by RV, or if they could imply design, is all another story. Again, it depends on the complexity of the event and on its functional meaning. Usually I prefer to analyze sequences, because the computation of the search space and of the functional space is much more direct. With exon shuffling and similar remixing events, it’s much more difficult, at least IMO.

    However, that such events do happen is not questionable. A fusion of two different components from different genes is not exactly common, but it happens. Sometimes with functional results. Some of these events can be due to transposon activity.

    Reutilization of domains, in more or less conserved form, is certainly more common, in the class of multidomain proteins. As I have said, I don’t believe that, in most cases, it is a mechanical reuse of the same domain with exactly the same context. We seem to differ a bit on that point.

    But there can certainly be cases where the same domain is used in similar ways, and without so much tweaking. In that case, not a lot of new information is probably generated in that kind of events. But again, it is difficult to assess all the variables in those cases (the probability of the event vs all possible similar events, for example).

    So, I stick to sequence analysis, not because it’s the only issue at stake, but because of procedural reasons.

    However, there can be no doubt that he generation of new functional sequences is the main engine in creating new protein function and complexity. That can in no way be denied. So, by sticking to sequence, I am anyway dealing with a very important part of the scenario.

    By the way, here is what I found about Jingwei:

    The origin of the Jingwei gene and the complex modular structure of its parental gene, yellow emperor, in Drosophila melanogaster.

    Mol Biol Evol. 2000 Sep;17(9):1294-301.

    Abstract:

    Jingwei (jgw) is the first gene found to be of sufficiently recent origin in Drosophila to offer insights into the origin of a gene. While its chimerical gene structure was partially resolved as including a retrosequence of alcohol dehydrogenase (ADH:), the structure of its non-ADH: parental gene, the donor of the N-terminal domain of jgw, is unclear. We characterized this non-ADH: parental locus, yellow emperor (ymp), by cloning it, mapping it onto the polytene chromosomes, sequencing the entire locus, and examining its expression patterns in Drosophila melanogaster. We show that ymp is located in the 96-E region; the N-terminal domain of ymp has donated the non-ADH: portion of jgw via a duplication. The similar 5′ portions of the gene and its regulatory sequences give rise to similar testis-specific expression patterns in ymp and jgw in Drosophila teissieri. Furthermore, between-species comparison of ymp revealed purifying selection in the protein sequence, suggesting a functional constraint in ymp. While the structure of ymp provides clear information for the molecular origin of the new gene jgw, it unexpectedly casts a new light on the concept of genes. We found, for the first time, that the single locus of the ymp gene encompasses three major molecular mechanisms determining structure of eukaryotic genes: (1) the 5′ exons of ymp are involved in an exon-shuffling event that has created the portion recruited by jgw; (2) using alternative cleavage sites and alternative splicing sites, the 3′ exon groups of ymp produce two proteins with nonhomologous C-terminal domains, both exclusively in the testis; and (3) in the opposite strand of the third intron of ymp is an essential gene, musashi (msi), which encodes an RNA-binding protein. The composite gene structure of ymp manifests the complexity of the gene concept, which should be considered in genomic research, e.g., gene finding.

    Interesting and complex, but I really cannot find any simple message that can be derived from these interesting facts, except that we still don’t understand a lot of things.

    To discuss better the other two examples you mention, Rubin and Tawfik , I would really need some more specific reference, because I have difficulties in finding exactly what you mention. On Tawfik’s site there is a general reference, and a long list of publications, but it would help to know what experimental results, in particular, are relevant in your opinion.

    Abstract theories are of no use, if they are not supported by specific facts, and I am looking forward to examining those facts through my ID filter. 🙂

  108. 108
    Dionisio says:

    .

  109. 109
    DATCG says:

    Gpuccio #103

    However, that interdomain sequence shows 2152 bits of homology between humans and sharks (callorhincus milii), with 1091 identities!

    Isn’t that a strong signature of functionality?

    Indeed it “appears to be Designed!” 😉

    I read/followed your first OP. Plan to read next one. Thanks for the work you’re putting into this, discussion and feedback.

    Inter-domains are fascinating. I’m mining information thru PubMed and Google Scholar. If you know other resources, would appreciate it.

    More research of inter-domains could turn up more functionality and/or deleterious effects by mutations, leading to disease. It appears to be a very delicate balancing act of energy levels and coordination between domains.

    Quantifying SATB1 and SATB2 through BLAST comparisons like you’re doing helps me understand the issues.

    On Neutral Theory,
    I’ll refrain from more comments. And wait for another post hopefully to discuss, learn varying opinions and insights 🙂

    Back to this OP, enjoying it!

  110. 110
    gpuccio says:

    DATCG:

    Thank you for the interest and for the kind words! 🙂

  111. 111
    Dionisio says:

    RodW and gpuccio:

    regarding RodW’s comment @91 and gpuccio’s comment @105(b) and my own comment @98:

    I agree with gpuccio that we all interpret things differently.

    But perhaps my main interpretation filter when reading science-related papers –which happen to be mainly from sources that are not ID-friendly– most probably has been influenced by my work experience among other things.

    For a substantial proportion of my existence I was pretty oblivious of and careless about the detailed meaning of things, even the things I was interested in. I was very superficial, immature. Probably I still am, but unlike then, at least now I’m aware of it. 🙂

    I remember attending a student meeting in the Lomonosov university auditorium, where the main speaker said something that made everybody -including myself- get up and give him a long standing ovation. The palms of my hands hurt from the enthusiastic strong applauding.

    Obviously back then I acted with a herd mentality, without reasoning. I liked what I heard without analyzing it in detail. It sounded like music to my ears. It was what I wanted to hear. I’m tempted to think that many people in that crowded auditorium that day were in similar situation, but that’s speculation.

    Years later, when I analyzed what that speaker had said at that event, I realized that it was a big mistake for me to have applauded, because once I understood what that speaker had said, I was totally against it. Now I know that I must test everything and hold what is good. But in my student years I was not aware of the importance of true meaning.

    Not too long ago some relatives of mine were booking hotel rooms for their planned trip to California. I jokingly told them to avoid Hotel California. Their reaction surprised me, because English is their first language, but not mine. They said there’s nothing wrong with Hotel California, because the most repeated phrase in that famous song was “such a lovely place”, which is said 4 times. Basically the phrase was taken at its face value out of context.

    Here I noticed that it seems like many folks don’t make any effort to understand the other party’s point of view. Thus they seem to talk past each other. The whole scene looks discouragingly bizarre.

    gpuccio’s OP is very technical. But it is written in an easy to understand language. Obviously people familiar with the concepts and terminology used by gpuccio can get more out of it than the folks like me who are practically biology-illiterate.

    That’s why I ask so many basic easy –maybe dumb?– questions. I could ask more, but don’t want to abuse gppucio’s courteous generosity. Instead I try to search for the answers myself. But sometimes I give up and ask the questions here.

    For a number of years I worked –under the direction of a brilliant engineer who was a role model in work dedication but who also was very demanding– on software development projects for engineering design programs. The final product existed in his mind long before the tech specs were written. But perhaps many details were not accounted for until the programming specs were written. And even then, a few details were omitted until the programmers realized that some conditions were not comprehensively treated in the programming documentation.

    This is where I want to point at now. The project leader, a very well educated and highly experienced engineer, who was very thorough in his technical analysis, could have missed some details about specific situations that had different possible solutions depending on the given conditions. However, when I was writing the programs, I could find some “black boxes” in the programming documentation. Sometimes they were intentionally placed there in the documentation, in order to be resolved at a later opportunity, maybe because someone had to be consulted outside the company or some technical meeting had to be scheduled to discuss the resolution. But sometimes the missing details resulted from inadvertent omissions.
    In some of those cases my fellow programmers or I could detect the detail omissions in the programming documentation. In those situations we reported the problem back to our supervisor or directly to the project leader.

    I think those years of constantly looking at details and trying to understand them as accurately as I could, made me so annoyingly picky about the nitty-gritty stuff.

    A couple of years ago someone I know well, read a paper that discussed post-translational modifications. However, the conclusions of the paper spoke about post-transcriptional modifications. Both concepts happen to have the same acronyms PTM. The person I know emailed the main author of the paper, who replied saying that it was an error that had not been caught by the peer reviewers.

    Sometimes the experts know so much about what they are reviewing that their minds betray them and correct the mistakes –i.e. the author(s) thought of “post-translational” but wrote “post-transcriptional”. Similarly the reviewers read “post-transcriptional” but thought of “post-translational”. Their knowledge betrayed them.
    BTW, the person who discovered and reported the inconsistency presented himself as a student but the author replied addressing the person as Doctor!!! Go figure that! 🙂

    Here in this thread we see that gpuccio is a doctor who is careful about details. His insightful OPs and follow-up comments show it. Other folks, like KF also seem very attentive to details. But some people don’t seem to care much about details. And I think that in science details are important, at least some times.

    Perhaps one reason why we see physicists and electrical engineers getting into the biological science research or academics is the advantage they have at looking at complex systems while paying attention to details.

    The two Systems Biology courses I watched online were taught by physicists, not biologists.

    Now you know the rest of the story. 🙂

  112. 112
    Dionisio says:

    DATCG @109:

    Indeed it “appears to be Designed!”

    But remember that’s just appearance. OK?
    It’s an illusion created by the quantum entanglement of the electrons in your brain.
    🙂

    Inter-domains are fascinating. I’m mining information thru PubMed and Google Scholar. If you know other resources, would appreciate it.

    Please, would you mind sharing with us what you find? Thank you.

  113. 113
    DATCG says:

    RodW,

    You say,

    “you’ll see that outside of the ID community no one thinks that evolution is on the verge of collapse.”

    As Gpuccio states, this is well known. But why not address the meat of Gpuccio’s Op? He’s given direct information you can challenge.

    Also, you make an error identifying ID against evolution. Not true. Many ID scientist, researchers, writers, etc., believe macro-evolution and common descent occurred. But not as defined by neo-Darwinism.

    neo-Darwinism is what’s collapsing. Evolutionary Biologist teacher at Cornell like Allen MacNeill stated Darwinism is Dead and neo-Darwinism is superseded. Actually, in trying to find the reference, Allen went farther on to say Modern Synthesis(neo-Darwinism) is Dead…

    “The modern synthesis is dead – long live the evolving synthesis!”

    And he comments…

    What is “dead” is the core doctrine of the “modern evolutionary synthesis” that based all of evolution on gradualistic changes in allele frequencies in populations over time as the result of differential reproductive success.

    This idea was essentially based on theoretical mathematical models originally developed by R. A. Fisher, J. B. S. Haldane, and Sewall Wright, with some experimental confirmation (using Drosophila) by Theodosious Dobzhansky and field observations (chiefly of birds) by Ernst Mayr (with some supporting observations on the fossil record by G. G. Simpson and plants by G. Ledyard Stebbins). Its high water mark was the Darwin centenial celebration at the University of Chicago in 1959, which most of the aforementioned luminaries attended, and which has been chronicled by Ernst Mayr and William Provine.

    However, cracks were already showing in the “synthesis” by 1964, when W. D. Hamilton proposed his theory of kin selection. They widened considerably in 1969 when Lynn Margulis proposed her theory of serial endosymbiosis. Then, in 1972, the dam broke, when Niles Eldredge and Stephen J. Gould published their landmark paper on “punctuated equilibrium. Not content to pull the rug out from under the “micro=macro” doctrine lying at the heart of the “modern synthesis”, Gould went on to publish yet another landmark paper with Richard Lewontin, this one undermining the “Panglossian paradigm” promoted by the founders of the “modern synthesis”: that natural selection is the primary mechanism of evolutionary change at all levels, and that virtually all of the characteristics of organisms are adaptive.

    And then Motoo Kimura and Tomiko Ohto dealt the “modern synthesis” its coup de grace: the neutral theory of genetic evolution, which pointed out that the mathematical models upon which the “modern synthesis” was founded were fundamentally and fatally flawed.

    Thus JUNK DNA was born.

    Which is why ENCODE is so important in todays debate. Epigenetics, EpiTranscriptome and why Dan Graur is so heated, angry and fighting with ENCODE today.

    You do realize there’s a large battle going on over evolutionary mechanisms and the failure of neo-Darwinism? This is happening within the evolutionary community.

    People are taking sides between Extending the Synthesis or scrapping it. Thus the historic meeting at Royal Society in England.

    They all realize they must extend it or it dies. Some, not many desire to scrap it. Rebuild on new grounds.

    Evolutionary Biologist Dan Graur said, “If ENCODE is right, evolution is wrong” See the Dan doubling-down post here at UD on JUNK DNA.

    ID is not the only critic of neo-Darwinism. Many evolutionary biologist, geneticist, microbiologist are openly critical of modern synthesis as an explanatory mechanism for new body plans and creative force.

    Take a look at Third Way Evolution, a group of scientist formed by Denis Noble, Shapiro and Koonin to name a few. All well respected evolutionist. But openly acknowledging neo-Darwinism has failed…

    The commonly accepted alternative is Neo-Darwinism, which is clearly naturalistic science but ignores much contemporary molecular evidence and invokes a set of unsupported assumptions about the accidental nature of hereditary variation. Neo-Darwinism ignores important rapid evolutionary processes such as symbiogenesis, horizontal DNA transfer, action of mobile DNA and epigenetic modifications. Moreover, some Neo-Darwinists have elevated Natural Selection into a unique creative force that solves all the difficult evolutionary problems without a real empirical basis. Many scientists today see the need for a deeper and more complete exploration of all aspects of the evolutionary process.

    So IDist are not alone, nor is GPuccio in declaring neo-Darwinism having collapsed. In fact, it’s long known to have problems going back to Kimura and Haldane’s dilemma. Long before 2006 admission by MacNeil. And more scientist are openly challenging and saying it’s not enough. It’s failed. From Alternberg 16 discussions to Third Way Evolution and more.

    I suspect as the old Darwinist dinosaurs go extinct, there will be a more robust and open debate and hopefully textbooks will reflect it.

  114. 114
    gpuccio says:

    Dionisio:

    Thank you for the details you gave us about your personal history. They are fascinating. 🙂

  115. 115
    gpuccio says:

    DATCG:

    Very well said. 🙂

  116. 116
    DATCG says:

    Dionisio #112

    Yep, was referencing Dawkins. 😉

    “Biology is the study of complicated things that give the appearance of having been designed for a purpose” Richard Dawkins

    Then there’s Fancis Crick’s quote, “Biologists must constantly keep in mind that what they see was not designed, but rather evolved.”

    Why? Why ‘must’ anyone do so?

    I think Reverse Engineering(a Design concept) is more fruitful in operational research.


    Inter-domains,
    OK 🙂

  117. 117
    DATCG says:

    Gpuccio, it’s amazing someone is not aware, or would not acknowledge the real upheaval in evolutionary synthesis these days.

    I was hoping to see more discussion and debate by RodW on the actual subject matter of your OP.

    Precisely because I learn more.

  118. 118
    wd400 says:

    Gpuccio, it’s amazing someone is not aware, or would not acknowledge the real upheaval in evolutionary synthesis these days.

    Well, I’m an evolutionary biologist and i can tell there really isn’t any “upheaval” these days. Calls to “extend the synthesis” have existed since the the 60s. For the most part, these have failed to demonstrate their importance, the rare exceptions include things like the nuetral theory which is now part of mainstream evolutionary biology.

    If you want to see the state of evolutionary biology these days I would check out the videos from the joint societies meeting recently published here.

  119. 119
    es58 says:

    Wd400@118 would you please comment on the op? Thank you!

  120. 120
    Dionisio says:

    gpuccio:

    Have you seen this?
    Would you comment on it?
    Thanks.

    Simplification, Innateness, and the Absorption of Meaning from Context: How Novelty Arises from Gradual Network Evolution
    Adi Livnat
    Evol Biol. 2017; 44(2): 145–189.
    doi:  10.1007/s11692-017-9407-x

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429377/pdf/11692_2017_Article_9407.pdf

  121. 121
    wd400 says:

    Wd400@118 would you please comment on the op? Thank you!

    I don’t really have the time to read it all, but at a glance it seems like a lot of these posts that I have commented on in the past. The sequence analysis is interesting enough, but this jump from the idea that sequences are conserved in some lineages yo the death of evolutionary biology is not really explained. (The closest thing to that is using BLAST bit scores as “functional information”, but there is no obvious reason to make this connection)

  122. 122
    gpuccio says:

    wd400:

    The sequence analysis is interesting enough,

    Well, thank you for that…

    but this jump from the idea that sequences are conserved in some lineages to the death of evolutionary biology is not really explained.

    But the point is simple enough, if you know ID theory. The point is that huge new functional information is beyond the reach of RV, for obvious reasons.

    The neo-darwinist argument. that it can be generated gradually through the magic of NS, si completely unsupported by any facts (and by any credible reasoning), and moreover would necessarily imply:

    a) very long evolutionary times

    b) detectable traces of intermediate forms from the supposed gradual pathway in the proteome

    Now, while it is rather intuitive that we have nothing of that kind for any known evolutionary situation, my reasoning in this OP (and in the ones that preceded it) tries to quantify the informational jump in specific proteins in a specific evolutionary context, by explicit objective arguments, so that it is apparent that this particular huge informational jump happened in a rather short evolutionary time, and left no traces in the proteome of any gradual pathway to it.

    (I know, I know, you or someone else will probably say that all evidence has been obviously destroyed, because neo-darwinian theory implies that all evidence in support of of itself will be destroyed: how scientific!).

    This is IMO strong, simple and objective evidence for ID theory, from undeniable observed facts.

    It’s interesting that you, as an evolutionary biologist, have dedicated four lines to comment it. 🙂

    But here is the last part of your comment:

    The closest thing to that [explaining why my argument implies the death of evolutionary biology, I suppose] is using BLAST bit scores as “functional information”, but there is no obvious reason to make this connection

    Well, my argument does not “demonstrate” the death of evolutionary biology (after all, empirical science never demonstrates anything), but is certainly trying to provide evidence int that sense! 🙂

    Now, I think that here you are saying that there is no obvious reason to use BLAST bit scores as “functional information” (please correct me if I have understood badly).

    And I ask you, who are an evolutionary biologist: why do you say that?

    The connection is based on very simple facts:

    a) I am considering and quantifying homologies in sequence that are not detected before the appearance of vertebrates. So, I believe that I am justified in defining those homologies as new information (at the time of its first appearance).

    b) I am considering and quantifying homologies in sequence that have been conserved up to the human form of the proteins. So, I believe that I am justified in defining those homologies as human-conserved information.

    c) I am assuming that the only possible explanation for that conservation throughout 400+ million years of evolutionary history is that those specific sequences have been preserved by purifying (negative) selection. Have you problems with that? have you some alternative explanation?

    d) I am assuming that in 400+ million years of evolutionary history, any sequence which evolves in two different lineages, and which is not extremely functionally constrained, would have been subject to neutral variation and drift, and would not exhibit any relevant homology in the two lines today, or just a vague trace of it. Have you problems with that, as an evolutionary biologist?

    e) Therefore, I am concluding that the sequences I am considering here are, at the time of their evolutionary appearance, new information that after its appearance shows to be under extreme functional constraint. IOWs, new functional information

    f) As the measure of the homology, in terms of bit score from BLAST, is an objective measure of what I have described in the previous points, I use it as a measure of functional complexity. Have you problems with that? I am sure you may have, but I am really looking forward to know what they are! 🙂

    So, these are the “reasons” behind my argument. Maybe they were not “obvious”, but now they are, I hope, rather explicit.

  123. 123
    wd400 says:

    As I say, I don’t really have the time (or the inclination if I’m honest) to go into a point by point discussion over this. I only discussed the OP at all because es58 asked me about it.

    In short, the results certainly show that this protein was cobbled together in the evolution of chordates (or perhaps lost in other lineages), and it (and its paralogs) have been under strong purifying selection since. The bit that is still lacking (even after the very long post above) is the evidence that this couldn’t be the result of mutation, recombination and selection. You’ve declared this multiple times, but no demonstrated it at all.

  124. 124
    gpuccio says:

    wd400:

    OK, thank you. I think this is the most I can get out of you, but it is appreciated. 🙂

  125. 125
    Dionisio says:

    wd400 @123:

    As I say, I don’t really have the time (or the inclination if I’m honest) to go into a point by point discussion over this. I only discussed the OP at all because es58 asked me about it.

    What else is new? Most politely dissenting interlocutors lack what is required in order to engage in serious discussions.

    The bit that is still lacking (even after the very long post above) is the evidence that this* couldn’t be the result of mutation, recombination and selection. You’ve declared this multiple times, but no demonstrated it at all.

    Where is the evidence that this* could be the result of mutation, recombination and selection?
    Can you point to it?

    (*) i.e. the relatively sudden –in evolutionary terms– appearance of complex functional specified information in proteins
    [Emphasis added]

  126. 126
    gpuccio says:

    Dionisio:

    I believe that wd400 has done what he could. And he has been honest in that.

    He has recognized that the biological analysis in my OP is correct, and that is already a great sign of good will, coming from am evolutionary biologist.

    We certainly could not expect that he said:

    “Oh, OK, you are right. These are convincing data to infer that neo-darwinism is not so good as it seems!!

    Not so likely! 🙂

    Of course you are right, his last statement is an example of the last line of defense that a neo-darwinist can recur to, when other arguments are lacking. It can be summarized as follows:

    “However, you cannot demonstrate that RV + NS (including recombination, if we want to be even more precise) could not do it”.

    In practice, they are saying that their theory remains true unless we demonstrate (with some mathematical theorem, I suppose) that it is wrong.

    But we know very well that the confutation of an empirical theory is not logical, but empirical. A theory must explain facts at the best of its ability. And that “best” must be convincing and appropriate.

    Now, it is evident that, as a rule, complex functional information does not arise from random variation.

    The neo-darwinian theory has the pretention to be an exception, due to the particular context of replicating individuals and competition (IOWs, the usual RV + NS stuff).

    Not convincing at all, because they happily ignore two fundamental flaws of their reasoning:

    a) The huge probabilistic barriers at stake

    b) The simple fact that complex functions cannot be deconstructed into a series of smaller functional (least of all naturally selectable) steps, and therefore cannot be built by gradual events (as any computer programmer well knows).

    So, the theory is flawed just from the beginning.

    But if someone (like the majority of scientists today) still insist in believing it is a good scientific theory, that someone should at least consider that the theory badly needs a couple of important supports from facts. For example:

    1) The graduality of appearance of complex sequences

    2) Very long evolutionary times for really complex objects

    3) Some realistic pathway or, at least:

    4) Some detectable trace of a pathway

    In the absence of such support, the theory is not only flawed, it is empiricallly irrelevant.

    Now, I have provided some well documented example of:

    1) Complex functional sequences, that

    2) Arise rather suddenly, IOWs in

    3) A very short evolutionary time, and for which

    4) Their is no idea of a gradual pathway, and

    5) No detectable trace of it.

    Is all that empirical evidence against the neo-darwinian paradigm? I believe it is.

    Of course, anybody is free to make his own mind about that.

    Moreover, I will remind again here that SATB1 and SATB2, while they are certainly a very good example of my reasoning (that’s why I have chosen them), are certainly no rare exception. I have already done similar reasonings for other proteins, like Prickle1 and Prickle2, and mentioned in the discussion many other examples, last of them ATM.

    It could be interesting to note that the best examples of my argument seem to be complex regulatory molecules, even if other kinds of molecules can certainly be mentioned too.

  127. 127
    es58 says:

    GPuccio@126:

    “3) A very short evolutionary time”

    Perhaps you’ve stated it above, and if so, you can point me to the post, but, can you identify an upper bound to the amount of time you’re referring to?
    Also, is there any way to show what kind of mutation rates would be necessary to get you to the amount of informational data you see being created (~1300 bits?) vs observed or assumed mutation rates. If these questions are out of line, no problem.

    Also, thanks for the post!

  128. 128
    Dionisio says:

    gpuccio @126:

    We certainly could not expect that he said:

    “Oh, OK, you are right. These are convincing data to infer that neo-darwinism is not so good as it seems!!

    Not so likely!

    There’s an old Spanish saying for this:

    “Pedirle peras al olmo”

    Asking an elm tree to produce pears.
    Or expecting pears from an elm tree.

    🙂

  129. 129
    gpuccio says:

    es58:

    “can you identify an upper bound to the amount of time you’re referring to?”

    It’s not easy, and I am not an expert of evolutionary times. The timeline I have used in my posts and graphs is the best I could derive from what I have read.

    However, always from what I have read, a reasonable upper limit for the transition we are discussing here could be 30 million years. But it could certainly be much less than that.

    The events from the Cambrian explosion on, even 100 million years after (which is more or less the time frame we are looking at) seem to take place very fast!

    “Also, is there any way to show what kind of mutation rates would be necessary to get you to the amount of informational data you see being created (~1300 bits?) vs observed or assumed mutation rates.”

    Well, some time ago I made a gross computation that brought me to propose 120 bits as a “biological probability bound”. That was done imagining our planet filled with bacteria, assuming a mean mutation rate and reproduction rate for bacteria, and considering a time frame of 5 billion years, and leaving about 20 bits of margin to make the thing really unlikely.

    So, 120 bits is IMO the upper margin of a search space that can be reasonably traversed by RV in the whole natural history of our planet.

    Here, of course, we should lower that threshold a lot. Firs of all we have only 30 million years at most available, and not 5 billion. Even more important, the population at stake here is certainly much, much lower (I have no idea how many lancelet-like beings could have been living in our earth’s oceans at the time, but it is certainly a much lower number compared to the 10^30 bacteria that I considered in my computation. Even reproduction rates are certainly slower. I am not sure about mutation rates, but you get the general idea.

    So, 1300 bits is a search space that is absolutely beyomd anything RV can traverse in the whole universe (remember, Dembski’s UPB is 500 bits). And these are, of course, exponential values: 1300 bits is a number which is about 350 orders of magnitude greater than 120 bits!

    Of course, these are the probabilistic resources, and refer to RV only. True NS can certainly lower those numbers. A little bit. If true NS could happen.

    But we have no trace that it happened.

    And how much NS are we speaking of?

    Let’s see it from the point of view of identities, leaving apart mere similarities.

    We have 731 conserved identities in the two molecules (a mean of 464 shared, + 139 + 128).

    So, let’s imagine, just for the sake of discussion:

    a) That each of those 731 AAs brings, individually, a detectable reproductive advantage, and therefore can be expanded by positive selection and then fixed by purifying selection.

    b) that such a fixing really happened, expanding the new 1 AA trait to all, or most, or some of the chordate population, before a new positive mutation could happen.

    IOWs, we are imagining that the specific new function, or functions, that vertebrate SATB1 and SATB2 perform in cartilaginous fish (and in all other vertebrates) could be deconstructed into 731 one AA steps, each of them bringing significant reproductive advantage, each of them naturally selected and expanded to a significant population.

    (I emphasize the expansion, because, even if darwinists try to belittle the concept, it’s the numeric expansion of the clonal population with the new trait that lowers the probabilistic barriers, and nothing else).

    O course, we are beyond any credibility here, even for the most fervent darwinist imagination, even for some hot science fiction of the lowest level!

    Because, as I said before, complex functions cannot, as a rule, be deconstructed into many smaller functional steps, least of all naturally selectable ones.

    However, let’s go on with our impossible scenario.

    Even so, given that we have 30 million years (at most) available, and 731 steps to implement, that means that each step (positive mutation, expansion to most of the population) should take place, in average, every 41000 years! Just the blink of an eye, in evolutionary terms.

    And, of course, we should have had 731 different expanded populations, of which no trace remains in the existing proteome. This is the old problem of the completely missing molecular intermediates, a problem that I have debated a lot of times with our kind interlocutors, always getting gross answers which, at best, were of the type: “They were eaten”; or: “Our theory implies that you can never find any evidence of this kind for it”.

    All this is simply empirically impossible. There is not even a trace of credibility in that kind of explanation. It has no scientific value at all.

    Those levels of functional information are found only in designed objects. They can be explained only by design.

  130. 130
    es58 says:

    GPuccio@129 Thankyou for your response.

    WD400@123:
    “The bit that is still lacking (even after the very long post above) is the evidence that this couldn’t be the result of mutation, recombination and selection. You’ve declared this multiple times, but no demonstrated it at all.”

    How does GPuccio’s response at 129 fail to answer your question? Thank you

  131. 131
    Dionisio says:

    gpuccio @129:

    We have 731 conserved identities in the two molecules (a mean of 464 shared, + 139 + 128).

    a) That each of those 731 AAs brings,

    Even so, given that we have 30 million years (at most) available, and 751 steps to implement, […]

    And, of course, we should have had 751 different expanded populations, of which no trace remains in the existing proteome.

    Please, help me with this:

    Lost the connection from 731 to 751.

    Is the difference associated with the number of essential AAs?

    Emphasis added.

  132. 132
    Dionisio says:

    .

  133. 133
    wd400 says:

    Hi es,

    I don’t really want to be dragged into a detailed discussion of this, I don’t have the time and making small comments can seem like sniping away without properly engaging.

    Here is what I would say about these kinds of posts generally.

    They lack any real connection to what we know from evoluionary biology. There is growing evidence that functional genes arise from random and/or intergenic sequences. There is no requirement that each amino acid be selected one after the other (these proteins are made from domains that are conserved well beyond the vertebrates, recombination can bring such domains together). There is no regard for the fact these genes have evolved down a species tree, the idea that you should be able to find every intermediate between an ancestral and moodern protein is obviously wrong as soon as you start thinking about trees. Assuming what happened to evolve is the only way a given function could arise (this functional information business) ignores the fact that proteins that have many interactions co-evolve with their interactants.

    As I say, I don’t have the time for a blow by blow account of this post or any other, all I would suggest is that people that are interested in sequence analysis check out the methods that evolutionary biology and genomics have developed to do this sorts of things. In the very least, all of these orthology/paralogy analyses are already done for every gene in places like ensembl.

  134. 134
    Dionisio says:

    @133:

    nonsense

  135. 135
    gpuccio says:

    Dioniso:

    The correct number is 731. At some point in the post I must have written erroneously 751, and then I went on a couple of times. I am correcting that.

    However, the computation for the time (41000 year) is correct: it was made with 731.

  136. 136
    Dionisio says:

    gpuccio,

    Thank you for clarifying that.

    I thought it was a mysterious Neo-Darwinian trick to account for the 20 AAs that are currently used to assemble the proteins, thus demonstrating that their apparent lack of valid arguments is only an illusion produced by quantum entanglement of the electrons in the brain. 🙂

    Have a good weekend.

  137. 137
    gpuccio says:

    Dionisio and es58:

    Again, I think wd400 has said honestly what he could say.

    We cannot hope to “convert” a convinced evolutionary biologist that our arguments are good. There is a problem of basic worldview (and scienceview). Moreover, they are those who are recognized by public opinion as detaining the truth, and we are only (for most people) a minority of strange guys! 🙂

    So, I am really grateful to wd400. He has been honest in evaluating the biological core of my OP, and he has (when “stimulated” by es58) clearly stated that he does not “want to be dragged into a detailed discussion of this”, that is absolutely something he is perfectly entitled to.

    He has, however, summarized clearly enough what his arguments would be. I have already commented about some aspects, and I will continue to do so tomorrow, for the sake of discussion.

    But I believe that we should respect wd400’s desire “not to be dragged”. We can certainly discuss some of the points that he has briefly summarized, without dragging him any more into our discussion.

  138. 138
    gpuccio says:

    Dionisio:

    No, it was only a typo (twice repeated!) produced by quantum entanglement of the electrons in my personal brain! Thank you for pointing to it. 🙂

    If I were a compatibilist, I could probably believe that it was a free choice… (OK, just kidding 🙂 )

  139. 139
    Dionisio says:

    gpuccio,

    I agree with your comment @137.

    I apologize for any inappropriate comments I may have written. I should learn to restrain my emotions. 🙂

    However, the comment @133 says “There is growing evidence that functional genes arise from random and/or intergenic sequences.” but it doesn’t provide any literature to back such a bold affirmation. Besides, your argument is based on complex functional specified information, like in the case of the proteins SATB1 & SATB2.

  140. 140
    Dionisio says:

    Copied from the OP:

    Here is a very brief recent bibliography:

    Essential Roles of SATB1 in Specifying T Lymphocyte Subsets

    SATB1 overexpression correlates with gastrointestinal neoplasms invasion and metastasis: a meta-analysis for Chinese population

    SATB1-mediated Functional Packaging of Chromatin into Loops

    Here is a brief recent bibliography about SATB2:

    Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex

    SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer

  141. 141
    Dionisio says:

    The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo
    Mubeen Goolam and Magdalena Zernicka-Goetz
    Development. 2017 Apr 15; 144(8): 1450–1461.
    doi: 10.1242/dev.144139
    PMCID: PMC5399666

  142. 142
    Origenes says:

    wd400@

    wd400: There is no regard for the fact these genes have evolved down a species tree, the idea that you should be able to find every intermediate between an ancestral and moodern protein is obviously wrong as soon as you start thinking about trees.

    GPuccio’s argument, as I understand it, is not about finding “every intermediate”, but rather about finding any intermediate. Unless you are willing to argue that, given trees, we should expect information jumps of thousands of bits and no intermediates whatsoever, you do not have a point.

    wd400: Assuming what happened to evolve is the only way a given function could arise (this functional information business) ignores the fact that proteins that have many interactions co-evolve with their interactants.

    An important fact that doesn’t sit well with your position. The information jump under discussion is in fact far higher.
    From the OP:

    … as a final note, please consider that these are very complex master regulators, which interact with tens of other complex proteins to effect their functions. The whole system is certainly much more irreducibly complex than we can imagine.

  143. 143
    gpuccio says:

    Origenes at #142:

    My friend, you have taken the words right out of my mouth! Thank you indeed. 🙂

    It is wonderful to see that it is not only my obfuscated mind that sees things that, to me, appear to be obvious.

    Your support is really precious!

    I will comment on wd400’s arguments later, when I have more time, but it is comforting to have some of the main points laid out so clearly by you.

  144. 144
    gpuccio says:

    Answers to wd400:

    In his post #133, wd400 has reiterated his legitimate desire not to be dragged into this discussion in detail. I respect his choice.

    However, as he has expressed in brief his main objections, and, being as usual very competent in his field, has raised some interesting points even in a few lines, I think I have a right to comment on those points.

    In no way this is an attempt to involve wd400 any more: he is absolutely entitled not to answer these further comments. Therefore, I will not address him personally, but just the ideas he has expressed.

    I will comment on each point separately, for further clarity. I will also happily use, where appropriate, the very good ideas expressed by Origenes at #142.

    As a start, I will briefly comment on his introductory remark:

    Here is what I would say about these kinds of posts generally.

    They lack any real connection to what we know from evoluionary biology.

    So, the ideas he is going to express are “general” objections to the reasonings presented in my OP, or to any other post “of the same kind”.

    And it is true. As we will see, he makes some very general points, certainly interesting and which deserve discussion, but they are not about the specifics of my data, which he seems to accept more or less, but about their general meaning, or the general approach. OK, that’s fine.

    And the first argument is really very, very general:

    “They lack any real connection to what we know from evolutionary biology.”

    And I would say: of course. For those who still have not understood it, I will say it again: ID theory is a paradigm which is strongly in disagreement with the standard approach of modern biology, based on the neo-darwinian synthesis. It’s not that they can be considered compatible, not even by the most die hard compatibilists. 🙂

    Does that mean that we in ID refuse modern biology? Not at all. Indeed, our best arguments are fully based on the result of modern biological research, even and especially research “inspired” by neo-darwinian ideas. Because facts are facts, and facts do not belong to any ideology.

    But it should be clear that the interpretation of many of those facts, especially those involved in the generation of functional information, is radically opposite between the two paradigms.

    In that sense, there can be no “connection” at all, not where the problem of the origin of biological information is at stake.

    More in next post.

  145. 145
    Dionisio says:

    gpuccio @144:

    And it is true. As we will see, he makes some very general points, certainly interesting and which deserve discussion, but they are about the specifics of my data, which he seems to accept more or less, but about their general meaning, or the general approach. OK, that’s fine.

    Did you mean “but they are NOT about the specifics of my data, […]”?

  146. 146
    gpuccio says:

    Dionisio:

    Yes, of course. Thank you. 🙂

  147. 147
    Dionisio says:

    gpuccio @144:

    […] our best arguments are fully based on the result of modern biological research, even and especially research “inspired” by neo-darwinian ideas. Because facts are facts, and facts do not belong to any ideology.

    Yes, that’s correct.

  148. 148
    Dionisio says:

    gpuccio @144:

    […] our best arguments are fully based on the result of modern biological research, even and especially research “inspired” by neo-darwinian ideas.

    Yes, for example, the threads “Mystery at the heart of life” and “A third way of evolution?” have many references to biology-related research papers, despite the fact that some of those papers (specially the evo-devo literature) are filled –or at least sprinkled– with archaic pseudoscientific hogwash based on the Neo-Darwinian just-so fairytales.

  149. 149
    gpuccio says:

    Answers to wd400:

    There is growing evidence that functional genes arise from random and/or intergenic sequences.

    Yes. And that is a very important issue in our debate. But I don’t see how that can help the neo-darwinian paradigm.

    It is true that the emergence of new functional genes from non coding sequences, rather than from pre-existing protein coding genes (as was previously thought) is gaining momentum.

    Here are a couple of recent papers about that, for example:

    De Novo Genes Arise at a Slow but Steady Rate along the Primate Lineage and Have Been Subject to Incomplete Lineage Sorting

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860702/pdf/evw074.pdf

    and:

    Young genes are highly disordered as predicted by the preadaptation hypothesis of de novo gene birth

    https://www.nature.com/articles/s41559-017-0146

    OK, first of all let’s clarify one important point: new functional genes must arise during evolutionary history. That they do arise even in more recent evolutionary history is no surprise.

    As said many times, I fully believe in common descent, therefore I fully believe that new genes arise in pre-existing biological beings. The real question is: how?

    Now, from all points of view, the emergence of a new gene from an existing gene is certainly more compatible with the neo-darwinian scenario (in the measure that we can speak of “compatibility”, for a theory that however cannot explain the rise of new complex information). Why? Because all neo-darwinian just so stories are of that kind: function emerges gradually from already existing function, through a continuum that has no reason to really exist, but that darwinists imagine must exist.

    But the emergence from non coding DNA?

    Well, for a new gene to arise from a non coding sequence, at least two things must take place:

    a) Transcription of the sequence must take place

    b) An ORF must be acquired, so that the transcribed sequence may be translated and become a gene

    Nobody knows exactly in what order the two things may happen, in the limited understanding that we have today of the issue. One hypothesis is that the non coding sequence is already transcribed, then acquires an ORF and is translated. Another hypothesis is that many ORFs exist but are not transcribed (“cryptic ORFs”), and at some point one of them is transcribed.

    Whatever. In both cases, one thing is for certain: unless and until the sequence is both transcribed and translated, no form of NS can take place for its function as a protein sequence, because no protein exists. IOWs, if a new gene emerges from a non coding sequence, whatever the modality, its “evolution” is completely neutral up to the moment it is both transcribed and translated. IOWs, up to the moment it becomes a new gene.

    That means that the emergence of a new gene, in the absence of any design intervention, is left purely to random variation. NS can have no role at all.

    Of course, darwinists imagine that after the emergence of the new gene, NS comes to the rescue, and operates its miracles. OK, faith has no limits. But remember, all the classic reasonings of neo-darwinism:

    a) Gradual evolution of function

    b) Recombination

    c) Starting near a functional island, and profiting of imaginary connections between functional islands

    and so on, here do not apply.

    Here we are starting from a completely random non coding sequence, according to the neo-darwinist theory. Until it becomes transcribed and translated, there is no reason at all that it may have any information about any protein sequence. None at all.

    So, the imagined NS should operate on a completely random sequence, when the sequence is already transcribed and translated. Not good for the neo-darwinian scenario. Not good at all.

    Just a few final remarks:

    1) The emergence of new genes from non coding DNA, for what we understand at present, seems to happen both as a transposon related event and independently from transposon activity.

    2) The second paper I quoted above seems to demonstrate that new genes, when they emerge, already have specific properties that “normal” non coding DNA does not have. IOWs, the long preparation of the sequence through apparently neutral variation, before any possible intervention of NS, seems to generate specific functional properties before the sequence is translated into a protein. How do you think that can happen?

    3) So much for the idea that non coding DNA is junk: it is a source of new genes, the clue to all functional evolution. 🙂

    OK, this was one of the most important points. There is certainly much more to be said about this issue, and much more to be discovered.

  150. 150
    Dionisio says:

    Very interesting explanation @149. Thanks.

    BTW, what do you think of the paper referenced @141?

  151. 151
    Mung says:

    gpuccio:

    OK, first of all let’s clarify one important point: new functional genes must arise during evolutionary history. That they do arise even in more recent evolutionary history is no surprise.

    Apparently three is a purpose to “junk DNA” after all!

  152. 152
    gpuccio says:

    Dionisio:

    Very interesting and very recent paper. So, SATB1 is really a master regulator, having a critical role already in the first decisions in the embryo!

    Another interesting point is the antagonistic role of SATB1 and SATB2 already in these first phases of development. That’s further evidence that the two molecules work as a whole system, irreducibly complex.

  153. 153
    gpuccio says:

    Mung:

    “Apparently there is a purpose to “junk DNA” after all!”

    You bet! Between ENCODE and Dan Graur, there is no game. 🙂

  154. 154
    Dionisio says:

    gpuccio,

    I see you wrapped up the discussion with wd400 very effectively.

    Did the discussion with RodW end?

    RodW was last seen @91 & @100 on July 19.

    Did you two exhaust the discussed topic?

    I look forward to reading your next article within this series.

    Thanks!

  155. 155
    Dionisio says:

    Here’s a link to the paper referenced @141:

    http://dev.biologists.org/cont.....9.full.pdf

  156. 156
    gpuccio says:

    Dionisio:

    I still have something to say about wd400 statements. As soon as possible… 🙂

  157. 157
    gpuccio says:

    Answers to wd400:

    There is no requirement that each amino acid be selected one after the other (these proteins are made from domains that are conserved well beyond the vertebrates, recombination can bring such domains together).

    IMO, these are two different concepts, not necessarily connected. Therefore I will treat them as separate issues.

    There is no requirement that each amino acid be selected one after the other

    I have imagined a situation where each aminoacid is naturally selectable and can be individually fixed because it is by far the most favourable to the neo-darwinian scenario.

    I want to be very clear about that. I don’t believe that complex functional are deconstructable into simpler functional, least of all naturally selectable, steps. This is specially true of complex regulatory structures, like the proteins we are considering here, but it is true of all complex enough functions. Such deconstructions are only (partially) reasonable in the tweaking of an existing function in a continuous functional space, but certainly not where a new biochemical or regulatory function must be built.

    However, as our imagination is potentially capable of it (even if we are not as well trained as a darwininst in conceiving just so stories). let’s pretend that some complex function can be deconstructed into, say, 500 increasingly functional and naturally selectable one aminoacid transformation steps. I know, I know, it’s impossible, but let’s pretend.

    I say that this is by far the most favourable scenario for neo-darwinists. Why?

    OK, let’s say that each one aminoacid mutation has ha probability, say, of 10e-4 to be observe in a given evolutionary time x. So, we need a time x+y (where y is the time to fixation, which can be very long, especially if the population is big) before we are in a favourable situation to wait for the second favourable mutation, which will need again approximately time x+y, and so on.

    So, let’s say that, to get a set of, say, 4 favourable mutations, we need about a time of (x+y)x4.

    Now, what happens if the function is not deconstructable into one aminoacid selectable mutations (which indeed is impossible), but rather into 4 aminoacid steps of naturally selectable functional mutation? OK, it’s impossible just the same, but let’s pretend.

    To be more clear, we are now imagining that, to have a naturally selectable step, we need to change 4 aminoacids in a specific way, and not only one.

    Now, what happens? We can get in one single process what required four steps in the previous scenario.

    In that scenario, the required time for the four steps was:

    (x+y)*4, IOWs:

    4x + 4y

    Now, it is “only” x1+y (there is only one time to fixation to be considered. That seems favourable, at a first impression, but…

    How much bigger is x1 (the time to get the mutation) if compared to x?

    If one aminoacid mutation with probability 10e-4 required approximately a time x, now the probability of getting 4 specific mutations in the same individual genome, each with 10e-4 probability, is the product of the 4 probabilities, IOWs 10e-16.

    Now, this number is much smaller than 10e-4, indeed it is 10e12times smaller (1000 billion times smaller). So, we can reasonably expect that x1, the time to get those 4 specific mutations, without any help from NS and any fixation, will be approximately 10e12 times longer than x. Not a trivial difference at all.

    So now the total time to get the same result that we got in time:

    4x + 4y

    in the first scenario, now will be:

    10e12 x + y

    Which is much less favourable than the first scenario, unless of course the time to fixation is really extremely long.

    So, the scenario where each single aminoacid substitution is naturally selectbale and is individually fixed (IOWs, where “each amino acid is selected one after the other”, is by far the most favourable scenario for neo-darwinism. Increasing the size of the selectable steps only implies for the neo-darwinian theory bigger and bigger catastrophes.

    I hope that the above reasoning is mathematically correct. I will be happy to acknowledge possible errors or imprecisions if anyone will show me what they are. 🙂

    More in next post.

  158. 158
    Dionisio says:

    Very interesting explanation. Thanks.

  159. 159
    gpuccio says:

    Answers to wd400:

    Now, the second part of the statement I considered in post #157:

    these proteins are made from domains that are conserved well beyond the vertebrates, recombination can bring such domains together

    Ah, the famous recombination argument. It seems to be the last defense of neo-darwinism, when everything else fails. Zachriel used to recur to it very often.

    But the point is: recombination is recycling of existing information. And if sequence information is recycled, it is usually recognizable.

    It is true that in SATB1 abd SATB2 we can recognize, from sequence homology, 5 sequences corresponding to known domains. And we have seen that the first two really have some significant homology with the same domains in pre-vertebrates. Moreover, those two sequences (corresponding to domains SATB1_L and CUTL) have significant homologies with the reference sequences of the relative domains (Expect valuse of 5.68e-49 and 1.98e-44 respectively). This is, therefore, the part of the protein that, in some measure, alredy “existed” in prevertebrates as a rather similar sequence. And I have fully ackowledged that, and computed it (the 154 bits of pre-existing information) in my reasoning.

    But the two sequences identified as CUT domains in BLAST (domains 3 and 4 in Fig. 2) have much lower homology with the reference sequences of the relative domains (1.46e-18 and 1.61e-18 respectively, more than enough to consider them homologues of the reference domain, but anyway homologues with rather different sequences), and, what’s more important, have no detectable homology at all in pre-vertebrates. That means that, even if they could have a structure correspondent to the reference domains (but I doubt that anyone has studied their structure in this particular proteins), the sequence is all new in vertebrates, and only very partially corresponding to the reference domain sequence. And, remember, this particular sequence, as it is, with its differences from the domain reference sequence, is conserved in these proteins for 400+ million years.

    The scenario is even more apparent for the 5th sequence recognized as domain, the HOX sequence, where the homology with the reference domain sequence is even lower (Expect 2.38e-08), and again no detectable homology in pre-vertebrates can be observed.

    This, without considering the interdomain sequences, which are conserved too, and do not correspond to any domain and have no detectable homologies in pre-vertebrates.

    Now my point is: these sequences (those corresponding to known domains) are anyway new in vertebrates, and conserved form then on. This is what the sequence analysis tells us.

    Could recombination have had some role in their generation?

    The answer is simple: no, not at all.

    Why? Because recombination can only remix sequences that already exist. How can recombination help generate new complex sequences, that did not exist before? If the sequences in SATB1 and SATB2 had been generated by recombination of similar sequences in pre-vertebrates, they still would exhibit some homology in pre-vertebrates, especially if those sequences are subject to purifying selection (and they are, because from sharks to humans they are conserved).

    But those sequences have no homology with sequences in pre-vertebrates. How can we think that they are the result of recombination?

    Look at the difference with the sequences in the first two domains: those do show homologies, with similar sequences in pre-vertebrates, especially the first domain, which is well represented in that category. The first and second domain together, in the bets pre-vertebrate hit, are responsible for those 154 bits that we had to subtract in our computation of “new” functional information in vertebrates.

    So, it’s perfectly possible that those sequences come from “recombination” (or any other form of reuse) from pre-vertebrates. With some differences, but a very well recognizable homology.

    Compare that to the complete absence of homology in pre-vertebrates for all the rest of the molecule. Here, certainly, recombination could have no role at all. Those sequences are new in vertebrates, and are retained after the first vertebrate split. They are new and functional. Recombination cannot explain them at all.

    More in next post.

  160. 160
    john_a_designer says:

    GPuccio @ 122,

    But the point is simple enough, if you know ID theory. The point is that huge new functional information is beyond the reach of RV, for obvious reasons.

    The neo-darwinist argument. that it can be generated gradually through the magic of NS, si completely unsupported by any facts (and by any credible reasoning), and moreover would necessarily imply:

    a) very long evolutionary times

    b) detectable traces of intermediate forms from the supposed gradual pathway in the proteome

    Now, while it is rather intuitive that we have nothing of that kind for any known evolutionary situation, my reasoning in this OP (and in the ones that preceded it) tries to quantify the informational jump in specific proteins in a specific evolutionary context, by explicit objective arguments, so that it is apparent that this particular huge informational jump happened in a rather short evolutionary time, and left no traces in the proteome of any gradual pathway to it…

    Indeed, the apparently “rapid” bursts and spurts we see in the evolutionary tree are not readily amenable to the Neo-Darwinian macro-evolutionary narrative. (Darwinism and Neo-Darwinism are better described as narrative that scientific theories.) It seems to me that sabt1 and sabt2, with their functional CSI at some point at least appear to have burst on the scene. Is assessment that correct? Of course, there are other possibilities. There are always other possibilities.

    In his book Darwin’s Black Box, Michael Behe asks,

    “Might there be an as yet undiscovered natural process that would explain biochemical complexity? No one would be foolish enough to categorically deny the possibility. Nonetheless we can say that if there is such a process, no one has a clue how it would work. Further it would go against all human experience, like postulating that a natural process might explain computers… In the face of the massive evidence we do have for biochemical design, ignoring the evidence in the name of a phantom process would be to play the role of detective who ignore the elephant.” (p. 203-204)

    Basically Behe is asking, if biochemical complexity (or IC) evolved by some mindless natural process x, how did it evolve? That is a perfectly legitimate scientific question. Notice that even though in DBB Behe was criticizing Neo-Darwinism he is not ruling out some other mindless natural evolutionary process, “x”

    Behe is simply claiming that at the present there is no known natural process that can explain how irreducibly complex mechanisms and processes originated. If he and other ID’ist are wrong then our critics need to provide the step-by-step-by-step empirical explanation of how they originated, not just speculation and wishful thinking. Unfortunately our regular interlocutors seem to only be able to provide the latter not the former.

    Behe made another point which is worth keeping in mind.

    “In the abstract, it might be tempting to imagine that irreducible complexity simply requires multiple simultaneous mutations – that evolution might be far chancier than we thought, but still possible. Such an appeal to brute luck can never be refuted… Luck is metaphysical speculation; scientific explanations invoke causes.”

    In other words, a strongly held metaphysical belief is not a scientific explanation.

    So why does Neo-Darwinism persist? I believe it is because of its a-priori ideological or philosophical fit with naturalistic or materialistic world views. Human being are hard wired to believe in something– anything to explain or make some sense of our existence. Unfortunately we also have the tendency to believe in a lot of untrue things.

  161. 161
    gpuccio says:

    john_a_designer:

    Behe has always been one of my favourite ID thinkers. He is really a remarkable man and scientist.

    You say:

    “So why does Neo-Darwinism persist? I believe it is because of its a-priori ideological or philosophical fit with naturalistic or materialistic world views. Human being are hard wired to believe in something– anything to explain or make some sense of our existence. Unfortunately we also have the tendency to believe in a lot of untrue things.”

    You are right.

    I am absolutely convinced that, if there were some other “naturalistic” (whatever it may mean) scientific explanation for biological functional complexity, the whole house of cards of neo-darwinism would be readily and happily dismissed as unsupported and unreasonable speculation. Which it is.

    Unfortunately, the only credible explanation for biological functional complexity remains some form of conscious design. And that cannot be accepted for dogmatic reasons and worldview prejudices.

    Neo-neo-neo darwinists (the third or fourth way, or whatever) are trying to create some biological “compatibilism”, invoking fashionable idols like some teleological principle or force of nature, or who knows what, but of course, like compatibilism, this is only an intellectual trick: purpose and cognition are only experiences of consciousness, and of conscious agents. They simply don’t exist in objects, they are experiences and representations of consciousness.

    So, in a world of deterministic free will, mindless purpose and intelligent stupidity, we can only wait that something change, and that real and true things become acceptable again.

  162. 162
    Dionisio says:

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  163. 163
    Dionisio says:

    The very few politely dissenting interlocutors that have dared to debate the discussed topic with gpuccio, have seen their very poor arguments crushed by the clear detailed explanations gpuccio has provided in his OP and comments.
    Looking forward to reading the next OP in this series.

  164. 164

    Excellent work GP. The very best.

  165. 165
    gpuccio says:

    UB:

    Thank you, my friend! 🙂

  166. 166
    Dionisio says:

    @159:

    So, it’s perfectly possible that those sequences come from “recombination” (or any other form or reuse) from pre-vertebrates. With some differences, but a very well recognizable homology.

    Are those sequences with recognizable homology with pre-vertebrates functional? If they are, do they perform similar or different functions as in pre-vertebrates?

  167. 167
    gpuccio says:

    Dionisio:

    “Are those sequences with recognizable homology with pre-vertebrates functional? If they are, do they perform similar or different functions as in pre-vertebrates?”

    OK, not a simple question!

    Let’s start with the first domain, the N terminal domain. It is representative of its own superfamily:

    N-terminal domain of SATB1 and similar proteins

    This is the information from NCBI:

    “SATB1, the special AT-rich sequence-binding protein 1, is involved in organizing chromosomal loci into distinct loops, creating a “loopscape” that has a direct bearing on gene expression. This N-terminal domain, which may be involved in various interactions with chromatin proteins, resembles a ubiquitin domain and has been shown to form tetramers, a function critical to SATB1-DNA interactions. The related Drosophila homeobox gene defective proventriculus (dve) plays a key role in the functional specification during endoderm development.”

    IOWs, in vertebrate proteins SATB1 and SATB2 the domain seems necessary for the tetramerization of the protein, an important functional step, but has probably many other functions, as it “may be involved in various interactions with chromatin proteins”.

    the same superfamily includes the similar domain in drosophila protein DVE, a protein with transcription factor activity and important regulator functions. Frankly, from what is known I would say that the two proteins (SATB proteins in vertebrates and DVE protein in drosophila are both important transcription regulators, but they have very different spectrum of activity.

    The highest homology hit between Drosophila DVE and the human proteome is with SATB2 (75.9 bits, 53%identities), and significant hits are only with SATB proteins, and nothing else.

    The homology between DEV and SATB proteins is essentially limited to this domain (about 100 AAs). For the rest, they are completely different molecules (human SATB proteins being, as we know, 763 and 733 AAs long, while drosophila DEV is 1021 AAs long.

    The second domain, CUTL, is again a representative of its own superfamily:

    CUT1-like DNA-binding domain of SATB

    This is the information from NCBI:

    “CUTL is part of the N-terminal region of SATB proteins, special AT-rich sequence-binding proteins that are global chromatin organisers and gene expression regulators essential for T-cell development and breast cancer tumor growth and metastasis. CUTL carries a DNA-binding region just as CUT domains do.”

    As said, it has a significant hit in Parasteatoda tepidariourum (the spider), but no significant hits in drosophila).

    In the spider, the hit is 83.6 bits, 52% identities.

    The spider protein is labeled as:

    “uncharacterized protein LOC107441355”,

    and is 595 AAs long. I don’t think that much is known about it.

    I hope this answers your question. 🙂

  168. 168
    Dionisio says:

    gpuccio @167:

    Thank you for the explanation. I need some time to chew and digest it. Needless to say that I’m learning more than I expected from this OP, as I did from the two that preceded. Looking forward to reading the next OP of this series.

    FYI – I’m copying your OP + follow up explanations into an off-line document so that I can partially quote it in Bioinformatics and/or Systems Biology-related discussions outside UD. Obviously I will cite you as the author and UD as the source of the text. Definitely I won’t take any credits for the information in the text.

    I may have to make minor proofreading corrections in order to make the text presentable to more discriminating audiences. I’ll share with you the proposed adjustments. At this point I just ask you for your consent. Thank you.

    PS. for example, @167:

    IOWs, in vertebrate proteins SATB1 and SATB2 the domain seems necessary for the tetramerization of the protein, an important functional step, but has probably meany other functions, as it “may be involved in various interactions with chromatin protein”.

    many?

    the same superfamily includes the similar domain in drosophila protein DVE, a protein with transcription factor activity and important regulator functions. Frankly, from what is known I would say that the two proteins (SATB proteins in vertebrates and DVE protein in drosophila are both important transcription regulators, but they have very different spectrum of activity.

    (SATB proteins in vertebrates and DVE protein in drosophila) are both important
    [missing ‘)’]

    [Emphasis added]

  169. 169
    gpuccio says:

    Dionisio:

    Of course you can. And please, go on with your activity as my personal editor. I am grateful for it! 🙂

  170. 170
    Dionisio says:

    gpuccio,

    Excellent! Thank you for the approval!
    And for promoting me up to personal editor of a doctor author.
    That sounds pretty “important” after being only a software developer for years.

    🙂

  171. 171
    gpuccio says:

    Answers to wd400:

    There is no regard for the fact these genes have evolved down a species tree,

    I really don’t understand the reasons for this strange statement.

    All my reasoning is based on common descent and on the concept of a species tree. I have tried at my best the commonly accepted ideas and timelines for the evolutionary tree that brought to vertebrates and on. I have tried to localize as precisely as possible the window of evolutionary time where the informational jump takes place. The concept of a jump itself has no meaning, if not in the light of such an evolutionary tree.

    So, why is my interlocutor stating that in my reasoning “there is no regard for the fact these genes have evolved down a species tree”? I don’t understand.

    the idea that you should be able to find every intermediate between an ancestral and moodern protein is obviously wrong as soon as you start thinking about trees.

    Why should “thinking about trees” make my ideas suddenly wrong?

    And, of course, I have never complained that we “should be able to find every intermediate between an ancestral and modern protein”. This is really obfuscation of my real thoughts.

    What I complain of is that we should be able:

    a) to find at least some intermediate (not every intermediate

    b) between the ancestor protein present in pre-vertebrates (presumably in chordates) and

    c) the sequence which had to be already present in the last common ancestor of vertebrates, and which has been conserved after that both in sharks and in the human lineage, after the split between cartilaginous fish and bony fish.

    So, two important errors in wd400 representation of my argument:

    Not every intermediate, but at least some intermediate (instead of none at all)

    We need intermediates not to the modern protein, but to the sequence that was already present in the last common ancestor of vertebrates, more than 400 million years ago, and that has been conserved thereafter. That sequence is, in no sense, “modern”.

    So, why should “thinking about trees” instantly obliterate the meaning and the value of this argument?

    By the way, the essential point of my counter-argument here had already been brilliantly expressed by Origenes in his post #142, in response to wd400. I quote from that:

    “GPuccio’s argument, as I understand it, is not about finding “every intermediate”, but rather about finding any intermediate. Unless you are willing to argue that, given trees, we should expect information jumps of thousands of bits and no intermediates whatsoever, you do not have a point.”

  172. 172
    gpuccio says:

    Dionisio:

    I have almost a veneration for software developers! 🙂

  173. 173
    Dionisio says:

    gpuccio @171:

    we should be able:
    a) to find at least some intermediate (not every intermediate [missing ‘)’?]

    b) between the ancestor protein present in pre-vertebrates (presumably in chordates) and

    c) the sequence which had to be already present in the last common ancestor of vertebrates, and which has been conserved after that both in sharks and in the human lineage, after the split between cartilaginous fish and bony fish.

    Not every intermediate, but at least some intermediate (instead of none at all)

    We need intermediates not to the modern protein, but to the sequence that was already present in the last common ancestor of vertebrates, more than 400 million years ago, and that has been conserved thereafter. That sequence is, in no sense, “modern”.

    Very clear point. So clear that even I can understand it.

    I believe that some folks may not understand it because they just don’t want to. The will to understand is required.

  174. 174
    Mung says:

    Hello gpuccio,

    Could I interest you in a side project. 🙂

    Could you perhaps take a look at opsins with particular respect to snails?

    http://theskepticalzone.com/wp/eye-mock-stupidity/

    (Assuming you haven’t already done a post on opsins!)

    The author of the book from which I quote in my OP over there at “The Charitable Zone” seems to think that opsins provide evidence for gradual evolution of the eye via natural selection.

    Yikes!
    http://genomewiki.ucsc.edu/ind....._of_opsins

  175. 175
    Origenes says:

    wd400: I don’t really have the time to read it all, but at a glance it seems like a lot of these posts that I have commented on in the past.

    You are mistaken wd400, you did no such thing. GPuccio has written several posts about the evolutionary history of proteins, but up till now you have studiously ignored all of them. You may like the idea that you have offered counter-arguments in the past, but that’s all pure fantasy, in fact, that never happened.
    Don’t worry it’s not your fault. There are no valid counter-arguments.

  176. 176

    Origenes, I really appreciate that you’ve called out WD400 straight up — no BS.

    If we have to suffer the dull headed face-painters like rvb (and others), then surely those that can actually engage the conversation should be called out for standing silent on the sidelines when ID proponents like Dr. Puccio make their arguments.

  177. 177
    wd400 says:

    Doesn’t take much googling to find places where I’ve tried to explained the relevance of phylogeny and the limitations of taking BLAST databases as complete records of diversity (eg https://uncommondescent.com/intelligent-design/an-attempt-at-computing-dfsci-for-english-language/, https://uncommondescent.com/intelligent-design/homologies-differences-and-information-jumps/). THere are probably others if you look hard enough.

    Reading those posts demonstrates the futility of this though, none of the comments (or, frankly, the ones I made above) have made a dent in the way these posts are written.

    The question of finding (or, actually inferring) ancestral intermediates is a strange one. First, such intermediates obviously exist, bacause the proteins are not 100% conserved, allowing us to infer ancestral states. If you look only at those amino acids are conserved then ask for the intermediates then obviously we won’t find them. It is also strange to ask think discontinuous jumps between clades is a problem and not a prediction of evolution down a tree. All vertebrates share ~30 million years of evolutionary history, variation that occured in that time are not available for study when we look at modern organisms.

    The idea that not finding homologies for all domains in non- (not pre!) vertebrate animals using blastp and default settings is evidence that these domains were not present in the ancestors of vertebrates is also strange. These domains are all present in modern non-vertebrates.

    Again, I don’t wish to get into a point-by-point discussion with posts that are as verbose as these ones, especially given how futile it seems to be.

  178. 178
    gpuccio says:

    Mung:

    I will give a look at opsins. It seems a very complex issue! 🙂

    From the genomwiki page you linked, this seems interesting for our discussion here:

    Early deuterostomes — represented today by living echinoderms, hemichordates, cephalochordates and urochordates — retained various opsin classes descended from the ur-bilateran (indeed eumetazoan) ancestor but never possessed imaging vision nor subsequently developed it except in one descendent lineage (vertebrates). One tunicate opsin specialized in the direction of parapinopsin but the main expansion and maturation of the opsin gene family took place very rapidly in the lamprey stem.
    Indeed at the time of divergence with jawed vertebrates, the last common ancestor possessed a full set of modern opsin genetic loci, furnishing four-color imaging ciliary opsin-based cone and rod vision with advanced oil-drop filtration. Intermediary states in chordate imaging vision development are no longer represented among extant species unless hagfish provides an intermediate node or better opsin retention occurs in additional urochordate genomes.

    Emphasis mine.

    Does that seem familiar? 🙂

  179. 179
    gpuccio says:

    Well, wd400, again after stimulation, has expressed some new thoughts.

    Unfortunately, I still have to finish my reasonings about his previous post. It will be difficult to stay updated.

    After all, my posts are “verbose”, so it’s all my fault! 🙂

  180. 180
    wd400 says:

    gp, these are not so much new as trying to underline what I referred to in the earlier comment. You are welcome to reply, but I am unlikely to follow anything up.

  181. 181
    gpuccio says:

    wd400:

    It’s fine with me.

  182. 182
    gpuccio says:

    Mung:

    Just to confirm what is written in the genomewiki link, here are two rather different opsins that both present a significant informational jump in vertebrates:

    a) Rhodopsin (P08100). 348 AAs.

    Jump from non vertebrates to vertebrates:

    1.091954 bits per aminoacid site

    380 bits

    b) Long-wave-sensitive opsin 1 (P04000). 364 AAs.

    Jump from non vertebrates to vertebrates:

    0.8901099 bits per aminoacid site

    324 bits

    But, of course, such verbose statements can have no interest for your kind interlocutors at TSZ, or for wd400, or for any other thinking person in the neo-darwinian field.

    And, after all, as wd400 says, “variations that occurred in that time are not available for study when we look at modern organisms”. But we have to believe that the intermediates existed, if he says so.

  183. 183
    gpuccio says:

    Origenes:

    “Don’t worry it’s not your fault. There are no valid counter-arguments.”

    🙂

  184. 184
    gpuccio says:

    Well, tomorrow I hope that I can finish my verbose comments on wd400’s previous post, and maybe add a few (verbose) words about his last one.

    For the moment, before going to sleep, I can only thank him again for being such a good inspiration for my verbose and futile activities. 🙂

  185. 185
    Origenes says:

    wd400 has argued that gaps are expected. For instance here (2014):

    … you wouldn’t expect to see intermediates if there were a set paths from A -> B -> … -> X, because intermediates will be replaced by more favoured variants. The branching nature of evolutionary process creates gaps in extant species/proteins/genes.

    If huge gaps, like the one between non vertebrates and the first vertebrates (WRT proteins SATB1 and SATB2), are to be expected, why is there no such gap between the whale shark and humans?
    Wd400 wants it both ways. If there are (huge) gaps, then this is expected and when there are no gaps then this is evidence for blind watchmaker evolution.

  186. 186
    gpuccio says:

    Origenes:

    Of course, small gradual gaps are expected in neo-darwinian theory. Not at all, IMO, such huge gaps of hundreds of bits as have been shown in my OPs and comments.

    That’s why science has to be quantitative, and not only rely on just so stories supported by dogmatic consensus.

    You are perfectly correct, if gaps are to be expected, why do we see them only at certain crucial passages, and much more in some proteins than in others?

    Regarding the “branching nature” of evolutionary process, he is again arguing against his same theory.

    A perfect cancellation of all the intermediate forms requires that each step is completely fixed, and that all alternative forms of the functional protein, those same alternative forms that had been fixed in the previous step, are completely cancelled.

    But the proteins that existed in non vertebrates are not cancelled by those that we find in vertebrates. Even today, in the human proteome, a lot of polymorphisms exist, some of them even certainly deleterious.

    How can you explain that a lot of apparently normal people harbor genes that favor specific tumors, or thrombosis, and so on?

    And yet we should believe that hundreds, thousand, maybe millions of molecular intermediates, all of them perfectly functional, so much so that they have been positively selected in the course of natural history, completely disappeared without leaving any trace of themselves?

    The important thing is that neo-darwinism remain unfalsifiable: there is no need to support the theory by molecular intermediates, even if the theory is based on molecular intemrdiates.

    There is no need to demonstrate that possible intermediates, even if only imagines, could possibly have been naturally selected, even if the theory is based on natural selection.

    There is no need to show in the lab some real pathway that can build new complex functional information by RV and NS alone, even if the theory is based on the existence of such pathways.

    No need at all to discuss with those who do not believe in the theory. The truth is where it is, how dare anyone doubt it?

  187. 187
    wd400 says:

    If huge gaps, like the one between non vertebrates and the first vertebrates (WRT proteins SATB1 and SATB2), are to be expected, why is there no such gap between the whale shark and humans?

    I’m not sure you’ve been reading this thread? These genes arose in the ancestors of vertebrates.

  188. 188
    wd400 says:

    How can you explain that a lot of apparently normal people harbor genes that favor specific tumors, or thrombosis, and so on?

    And yet we should believe that hundreds, thousand, maybe millions of molecular intermediates, all of them perfectly functional, so much so that they have been positively selected in the course of natural history, completely disappeared without leaving any trace of themselves?

    How old do you think the average disease allele is in human populations? How many do you think we share with chimps? Or elephants? (You don’t even need selection for ancestral variatns to die off — drift will do it just fine).

  189. 189
    Dionisio says:

    gpuccio @179:

    After all, my posts are “verbose”, so it’s all my fault!

    Please, keep them as verbose as you can. Thanks!

  190. 190
    Dionisio says:

    gpuccio @182:

    But we have to believe that the intermediates existed, if he says so.

    Of course! it’s all a matter of faith.
    No discussions allowed.

    Also, it’s obvious that we don’t understand evolution, whatever that means.

    🙂

  191. 191
    Mung says:

    But we have to believe that the intermediates existed, if he says so.

    You simply have to love a theory that wipes out the evidence that would support it.

    If we claimed that goddidit, but wiped out his tracks, we’d be laughed at. Goddidit but made it look like evolution is one of my personal favorites.

    But I don’t really believe wd400, because nothing is there to prevent gene duplication so that one gene can evolve into the new form while the other remains. That the evidence got wiped out is just too ad hoc and self-serving.

  192. 192
    wd400 says:

    The important thing is that neo-darwinism remain unfalsifiable: there is no need to support the theory by molecular intermediates, even if the theory is based on molecular intemrdiates.

    There is no need to demonstrate that possible intermediates, even if only imagines, could possibly have been naturally selected, even if the theory is based on natural selection.

    There is no need to show in the lab some real pathway that can build new complex functional information by RV and NS alone, even if the theory is based on the existence of such pathways.

    No need at all to discuss with those who do not believe in the theory. The truth is where it is, how dare anyone doubt it?

    This is just silly, of course.

    There are plenty of cases where we can reconstruct ancient proteins, and even measure their function (review here for an e.g.). But in cases where a gene arises in a relatively long inter-node in a tree those methods will not work.

    Instead, we can look a the constituent parts of the gene (in this case containing motifs that exist across the animal tree) and we can to look at more modern genes to understand the processes that contribute the origin of new genes and their early evolution. That’s a very rich field of research at present. Here are a couple of relevant papers (1, 2, 3,4), there are many more for anyone that is interested.

  193. 193
    Mung says:

    gpuccio, I hope I haven’t chosen something that will be a huge time sink for you!

    The protein family of opsins is very large, with more than 1,000 different opsins having been described so far (Terakita 2005). They fall into different groups (‘subfamilies’) with different functional properties, especially concerning the associated G-protein (Terakita 2005).

    – Andreas Schmidt-Rhaesa. The Evolution of Organ Systems (Oxford Biology)

  194. 194
    ET says:

    wd400:

    These genes arose in the ancestors of vertebrates.

    Question begging.

  195. 195
    Dionisio says:

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  196. 196
    gpuccio says:

    wd400:

    “How old do you think the average disease allele is in human populations? How many do you think we share with chimps? Or elephants? (You don’t even need selection for ancestral variants to die off — drift will do it just fine).”

    As it seems that you are taking a more active part in the discussion, I will answer some points later, but for the moment just a very simple question:

    How is it that we can keep 80-90% of junk DNA in our genome, while millions of functional molecular intermediates have simply been cancelled in the course of evolution?

    Who decides what dies off and what doesn’t?

  197. 197
    DATCG says:

    @177 WD400,
    You commented you already stated info to counter Gpuccio about limitations using BLAST in another post on UD.

    I was curious and looked through the two links you provide. 1st link, zero reference from you on BLAST. 2nd link, no mentions from you on BLAST.

    Only Gpuccio mentioned BLAST in first link.

    Alicia used BLAST in 2nd link, debating Gpuccio. And a few others mentioned Blast, from Dionisio to Me Think. Unless I missed it, search turned up nothing on BLAST by you in the two links your provided.

    Can you reference a specific comment so I can read why you think BLAST is inappropriate? Or, link it. Or state it here. I’m curious, thanks.

    You also stated this…
    “Natural selection removes intermediates, after all.”

    While this OP discusses proteins, do you expect
    Natural Selection to remove the fossil record as well?

    Are you advocating Gould’s Punctuated Equilibrium?

  198. 198
    Origenes says:

    wd400@

    wd400:

    Origenes: If huge gaps, like the one between non vertebrates and the first vertebrates (WRT proteins SATB1 and SATB2), are to be expected, why is there no such gap between the whale shark and humans?

    I’m not sure you’ve been reading this thread? These genes arose in the ancestors of vertebrates.

    You mean ‘the missing ancestors’, I suppose. Anyway, you claim that huge gaps are to be expected, so here is my question again: why is there no such gap anywhere between the whale shark and humans?
    Why is it that there is no bad news for Darwinism? Why is it thta smooth intermediates and a total absence of intermediates is explained with equal ease?

  199. 199
    gpuccio says:

    Mung:

    “The protein family of opsins is very large, with more than 1,000 different opsins having been described so far (Terakita 2005). They fall into different groups (‘subfamilies’) with different functional properties, especially concerning the associated G-protein”

    How strange that there are so many surviving. I supposed neo-darwinain evolution or drift should have reduced them to a few! 🙂

  200. 200
    Dionisio says:

    gpuccio,

    How strange that there are so many surviving. I supposed neo-darwinain evolution or drift should have reduced them to a few!

    There’s nothing strange about that. It’s just that we don’t understand Neo-Darwinian evolution, whatever it means.

    🙂

  201. 201
    gpuccio says:

    wd400:

    “This is just silly, of course.”

    OK. It is strange that, while I have written a number of “verbose” and rather detailed comments about your few lines (see posts #144, 149, 157, 159, 171), and you refrained from any comment. But you seem ready to intervene when, in your opinion, I say something “silly”. Is it possible that I smell some condescension on your part? 🙂

    OK, let’s go to your links. While I have not access to the 2017 review, and the abstract is not telling (a good reason for me to abstain from any comment), I have looked at the other 4 links, and I am surprised.

    With the exception of the first one (an experiment with random sequences in bacteria, that is too vague to mean anything substancial), the other three could have been well quoted by me in support of the reasoning I made in my post #149. Indeed. your link #2 was quoted by me in my post #149! Thank you for adding a couple of new links that support my view that new genes are designed from non coding DNA.

    You could maybe give a look at my post #149, perhaps even read it, especially the part about NS not applying to the evolution of non coding sequences.

    And maybe reflect on my real silly statement:

    The important thing is that neo-darwinism remain unfalsifiable: there is no need to support the theory by molecular intermediates, even if the theory is based on molecular intemrdiates.

    There is no need to demonstrate that possible intermediates, even if only imagines, could possibly have been naturally selected, even if the theory is based on natural selection.

    There is no need to show in the lab some real pathway that can build new complex functional information by RV and NS alone, even if the theory is based on the existence of such pathways.

    Now, I will try to clarify one point that is really important. When I speak of neo-darwinian pathways “that can build new complex functional information by RV and NS alone”, and I say that we have none, I mean exactly and literally that:

    A pathway more or less explicitly demonstrated that can build new complex functional information by RV and natural selection alone.

    It is no answer to that to:

    a) show that complex functional information arose in the course of natural history. Of course it arose. My OP here is based on that fact. The problem is: how?. How can we explain that?

    b) argue that there is some continuity in proteins throughout natural history, in the sense that we can recognize molecular ancestors because some domains are already present before. Of course that is true. I believe in common descent, and in the contituity of proteins, supported by design interventions that add the necessary new functional information. I have fully considered that in my analyisis in the OP here, when I have shown the part of the protein sequence that already has sequence homologies in non vertebrates, I have quantified that information at its highest value (154 bits) and I have subtracted that value fron the total of new functional information generated in the transition to vertebrates.

    You have not commented at all on my strong statement that complex functions cannot be deconstructed into simple intermediate steps, all of them naturally selectable, each of which needs to be fixed.

    Let’s forget for a moment the of the vanished intermediates. OK, you believe that all of them were conscientiously eaten. We will go back to that point.

    But what about the deconstruction?

    Let’s go again to the 731 conserved AAs that are detectable for the first time in sharks.

    So, how do you suggest that we can deconstruct that sequence into simpler, functional, naturally selectable steps?

    I have reasoned about that in my post #157. And made some quantitative considerations, too. Maybe you could read it.

    So, what do you suggest? 731 one-aminoacid naturally selectable steps? Each conferring a reproductive advantage? Each selected and fixed in the population?

    Or rather 182 4 AAs naturally selectable steps?

    Or do you like it better in twos, or threes, or tens?

    Or do you believe that neutral drift has a role? If so, I would just remind you that all neutral events are completely random with respect to functional sequence space, and therefore do not change in the least the probability barriers. Which are those we know they are.

    IOWs, random evolution by neutral variation is completely useless to build complex functional information. You have to rely only on NS, and therefore selectable steps, steps that are fixed in the population because they confer an advantage.

    That would be showing a neo-darwinian pathway that can build new complex functional information. To identify the intermediates. To explain, and maybe test, if and why they would be naturally selectable. To understand what they are, how many of them exist, how big is the transitition between steps, what probabilistic resources, including evolutionary time, are needed for a realistic random search that can find each candidate to a transition, and for a realistic fixation, given a realistic reproductive advantage (and, possibly, not too much interference from random drift and from Haldane’s dilemma).

    That is science: show examples, facts. Quantify.

    And, above all, respect the basic principle of science:

    No theory is good unless and until we support it with good facts.

    And not, as it often seems to be today:

    My theory is true because I say so, and unless and until you prove it false beyond any possible doubt!

  202. 202
    Dionisio says:

    gpuccio @167:

    As said, it has a significant hit in Parasteatoda tepidariourum (the spider), but no significant hits in drosophila).

    In the spider, the hit is 83.6 bits, 52% identities.

    The spider protein is labeled as:

    “uncharacterized protein LOC107441355”,

    and is 595 AAs long. I don’t think that much is known about it.

    Please, let me disagree with you on this. Much more is known about the spider. Check this out:
    https://www.youtube.com/embed/IC225eKspGM

  203. 203
    Mung says:

    How strange that there are so many surviving. I supposed neo-darwinain evolution or drift should have reduced them to a few!

    Walter ReMine described evolutionary theory as a smorgasbord. I think he nailed it.

  204. 204
    Mung says:

    There is no need to demonstrate that possible intermediates, even if only imagines, could possibly have been naturally selected, even if the theory is based on natural selection.

    This is exactly the case in my OP over at TSZ. The author says that natural selection seems to have invented the camera-type eye more than once and claims that a complex eye can evolve from an eye spot in about 360,000 years.

    His evidence for the former claim is the evidence for common descent. Apparently if you accept common descent you have to accept that natural selection did it.

  205. 205
    Dionisio says:

    Interesting how we humans interpret facts differently.

    For example, about 6 days ago, on July 19, RodW posted a comment @75 saying:

    “I have a feeling this thread is dead […]”

    On the same day @76 I asked him:

    “Why do you have such a feeling? What makes you thing that way?”

    I haven’t seen RodW’s reply yet. But that’s fine. I’m used to not getting my questions answered by the politely dissenting interlocutors. A professor complained that my questions are dishonest. Maybe because I used a tricky word (“exactly”) in a subliminal way to make it unnoticeable to the politely dissenting interlocutors. Oh, well. 🙂

    Now what is interesting is that –contrary to RodW’s perception– this thread was not dead on July 19th. Actually, it doesn’t seem dead yet.

    Here’s an interesting piece of simple statistics that shows that the discussion here still goes. Eventually the politely dissenting interlocutors will run out of things to say and the thread will hibernate, though it could remain as a confy corner for friendly chats. But in any case the topic may remain hot for an unforeseeable future.

    4 days after RodW’s wrong assessment:

    July 23, 2017 Popular Posts (Last 30 Days)

    [1] Information theory is bad news for Darwin: Evolutionary… (1,299)

    [2] John Sanford: Darwin a figurehead, not a scientist (1,213)

    [3] Is Mathematics a Natural Science? (Is that important?) (1,210)

    [4] Is OOL Part of Darwinian Evolution? (1,208)

    [5] Interesting proteins: DNA-binding proteins SATB1 and SATB2 (1,039) [9 days since started]

    July 24, 2017 Popular Posts (Last 30 Days)

    [1] Information theory is bad news for Darwin: Evolutionary… (1,302)

    [2] Interesting proteins: DNA-binding proteins SATB1 and SATB2 (1,252) [10 days since started]

    [3] John Sanford: Darwin a figurehead, not a scientist (1,213)

    [4] Is Mathematics a Natural Science? (Is that important?) (1,210)

    [5] Is OOL Part of Darwinian Evolution? (1,210)

    July 25, 2017 Popular Posts (Last 30 Days)

    [1] Interesting proteins: DNA-binding proteins SATB1 and SATB2 (1,306) [11 days since started]

    [2] Information theory is bad news for Darwin: Evolutionary… (1,302)

    [3] John Sanford: Darwin a figurehead, not a scientist (1,213)

    [4] Is OOL Part of Darwinian Evolution? (1,211)

    [5] Is Mathematics a Natural Science? (Is that important?) (1,210)

    Dead thread?

    🙂

  206. 206
    Dionisio says:

    Mung @24:

    Apparently if you accept common descent you have to accept that natural selection did it.

    Does gpuccio agree with that? 🙂

  207. 207
    gpuccio says:

    Mung:

    How’s life at TSZ?

    Do old friends, like Elizabeth, Mark Franck, Petruschka and Zachriel, still post there?

  208. 208
    gpuccio says:

    Dionisio:

    You know all about spiders! 🙂

    It’s thrilling to be at the first place! 🙂 🙂

    It doesn’t matter if we accept common descent. We have to accept that natural selection did it, whatever! 🙂

    Even us, who don’t understand Neo-Darwinian evolution, whatever it means. 🙂

  209. 209
    Mung says:

    Do old friends, like Elizabeth, Mark Franck, Petruschka and Zachriel, still post there?

    No, No, Yes and No. Even Patrick (aka MathGrrl) has left.

    Tom English and Joe Felsenstein still post.

    The list of people I have on ignore there has grown to 14 which probably says about all that needs to be said about it, lol.

  210. 210
    gpuccio says:

    Mung:

    Petruschka has always been a die hard! 🙂

  211. 211
    ET says:

    Petruschka has always been a die hard!

    A die hard what, is the question.

  212. 212
    gpuccio says:

    ED:

    If I remember well, he had his (few) ideas, and he was very stubborn about them. But, in general, it was possible to discuss with him for some while.

  213. 213
    gpuccio says:

    Answers to wd400:

    Now, I would like to complete my answers to wd400’s statements in his post #133.

    His last argument there was the following:

    Assuming what happened to evolve is the only way a given function could arise (this functional information business) ignores the fact that proteins that have many interactions co-evolve with their interactants.

    Again, I don’t understand how that can be considered an argument in favor of the neo-darwinian model. It is, indeed, quite the opposite.

    I thought that I had been clear enough in my OP:

    “And, as a final note, please consider that these are very complex master regulators, which interact with tens of other complex proteins to effect their functions. The whole system is certainly much more irreducibly complex than we can imagine.”

    Now, if a regulatory protein (and these proteins are indeed master regulators!) performs its function by interacting with a lot of other proteins (as is the case here) the only reasonable conclusion is that the whole regulatory system must be exceedingly irreducibly complex. Because the function (the correct regulation of many important cell processes, in different contexts) can be implemented only if all the “actors”, or at least most of them, are present and correctly working and interacting.

    Now, let’s suppose that 10 more proteins must be present and working to cooperate with SATB1 and SATB2 (there are probably more, but just to discuss). wd400 says that our proteins (the SATB proteins) will “co-evolve with their interactants”. Whatever that means, it seems that now we have not only 1300+ bits of functional information (and 731 identities) to explain in SATB1 and SATB2, but also a lot of other new functional information that we can find and quantify in the 10 accessory proteins. To get just one regulatory network. Among the many that exist in the cell.

    Even with my wildest imagination, I cannot see how that helps the darwinist cause.

    By the way, the essential point of my counter-argument here had already been brilliantly expressed, again, by Origenes in his post #142, in response to wd400. I quote from that:

    “An important fact that doesn’t sit well with your position. The information jump under discussion is in fact far higher.”

    With this post, I hope that I have completed my “impersonal comments” to wd400’s post #133 (a post really remarkable for its ability to summarize in a few lines many of the most frequently used arguments in favor of neo-darwinism).

    But, after that, wd400 has come back to the discussion with a few other posts, so maybe my verbose inspiration is not yet exhausted… 🙂

  214. 214
    Mung says:

    Even with my wildest imagination, I cannot see how that helps the darwinist cause.

    Thank god nothing ever gets stuck on a local optima on the fitness landscape where we can see how it was before it become perfected by natural selection.

  215. 215
    ET says:

    gpuccio- from what I remember Petrushka was fond of equivocating and steadfastly refused to understand what ID was saying.

  216. 216
    gpuccio says:

    ET:

    I agree that he was obstinate. However, I think that he had some moderately honest and dependable obstinacy.

    In the end, I would say that all our interlocutors from the other side “refuse to understand what ID is saying, especially when it is obvious that ID is right. They occasionally become more interested, when they believe that they have found some obvious error in ID thinking.

    Nobody from the other side really wants to “understand what ID is saying” (except maybe some very rare exceptions).

    But they do that with different personal styles. Some are simply arrogant, others condescending, others obstinate, others passionate, others patient, others simply obtuse or in bad faith. Some I have learned to respect, others to tolerate.

    Many, I simply try to ignore (as Mung says).

  217. 217
    john_a_designer says:

    Typically (and IMO justifiably) Darwinists and other naturalistic evolutionists criticize scientifically minded creationists for invoking the God-of-the-gaps argument to explain the very real gaps in the phylogenetic tree. It is indeed fallacious for creationists to argue that the gaps are strong or overwhelming evidence of supernatural intervention. However, that doesn’t eliminate a supernatural cause as a possible explanation. The honest answer is at present is that we don’t know. Furthermore, no one can honestly eliminate the possibility that there could someday be a scientific explanation.

    I once asked a creationist friend exactly what God created in the gaps and how he created it. He confessed to me that he didn’t know.

    However, a Darwin-of-the-gaps argument is just as fallacious. Unless you can somehow empirically describe step-by-step-by-step how natural selection (NS + RV) was able to bridge the gaps you don’t know. And you are certainly can’t claim that NS + RV is the only mechanism or that it is a ubiquitous explanation. It is not a falsifiable scientific explanation to argue that because NS + RV could explain common descent that it does. Of course, philosophically that’s a possibility but a philosophical explanation is not a scientific explanation.

  218. 218

    The materialist says that life is the product of unguided chance and necessity.

    The ID proponent says that life is the product of design; it is the most well-supported explanation.

    The materialist defends his position by saying that the ID proponent is merely filling gaps in our knowledge with a completely unnecessary entity.

    The ID proponent defends his position by recalling the evidence from IC, genetics, semiosis, etc.

    The distinction between these two positions is that one is falsifiable, while the other is not.

  219. 219
    Dionisio says:

    Isn’t the intelligent design (ID) paradigm based on what is known instead of the unknown?

    Then why do some folks like to associate ID with knowledge gaps?

    Where is such association taken from?

    The knowledge gaps in biology just raise questions that must be answered by discoveries made through scientific research, thus shedding more light on the elaborate cellular and molecular choreographies of complex functionally specified information orchestrated within the biological systems. Every major discovery seems to confirm the ID paradigm. However, as some outstanding scientific questions get answered, new ones are raised, setting new goals for the scientists to pursue in future research.

  220. 220
    Origenes says:

    GPuccio: In the end, I would say that all our interlocutors from the other side “refuse to understand what ID is saying, especially when it is obvious that ID is right. They occasionally become more interested, when they believe that they have found some obvious error in ID thinking.

    Indeed. I have never witnessed a materialist winning a non-trivial argument.

    Upright BiPed: The materialist says that life is the product of unguided chance and necessity.

    Exactly right. If life would be the product of necessity only, then intelligent design would still be the best explanation — after all who set the whole thing up? “Unguided chance” is what the materialist needs to get rid of design.
    However, if life is the product of unguided chance, then the same goes for materialist conjecture about unguided chance. And, unfortunately for the materialist, we have no reason to trust any conjecture produced by unguided chance …

  221. 221
    john_a_designer says:

    The problem is that neither chance nor necessity are causes. They may be descriptive of the way certain kinds of causes appear to operate but they are not in and of themselves causes. So to just invoke “chance” or “necessity” is to make a vague appeal to something vague and metaphysical. Is empirical science about invoking vague and metaphysical explanations?

  222. 222
    gpuccio says:

    john_a_designer:

    As I see things, there is no gap at all. I never speak of gaps.

    I speak of information jumps. An information jump is not a gap. It is an observed fact.

    So, we observe, or more precisely infer at the best of our understanding of natural history (it’s not easy to observe directly things that happened millions of years ago), that proteins SATB1 and SATB2, as they appeared in vertebrates, exhibit a new specific configuration, conserved thereafter, which implies 1300+ bits of conserved, therefore most certainly functional, information, and 731 conserved identities.

    This is the fact. Not a gap. A fact.

    The simple question is: does such a fact need some explanation, or is it something that we routinely observe under known laws?

    The answer is simple: the fact needs some explanation, because it is not something that we routinely observe under known laws. Indeed, it is something that we never observe under known laws.

    Maybe chance and necessity are not causes. But laws are causal patterns. I would say that chance and necessity are some model, made by us, of how laws work. The working of one single well defined law, regularly confirmed by facts, is what we call necessity. A summary way of describing mathematically, with limited but definite efficacy, how a system where many different laws and variables are at stake evolves is what we call chance.

    So, we need an explanation for functional information, including the 1300+ bits of it observed in our two proteins at the appearance of vertebrates, because he laws we know, both if described in terms of necessity or in terms of chance, cannot explain that kind of observed fact.

    Again, no gaps at all, of any kind, here.

    Moreover, I suppose that even our kind interlocutors will probably agree that such a kind of observed fact needs some explanation. So much so, that they have a complex specific model to “explain” it, what they call the neo-darwinian theory.

    Again, it’s not a problem of gaps: the only legitimate question is: does that model explain the observed fact?

    For a lot of reasons that I have tried to summarize, in part, in my verbose interventions here, my answer is, strongly, No!

    Now, we could certainly stop here and say that we have no scientific explanation at all for that fact. After all, a mystery is better than a wrong explanation, science.

    I can agree, but there is an important aspect of the question that must be considered. The fact is that we do observe abundant new functional information under known laws: in artifacts.

    Doe that mean that artifacts need divine intervention? Are they some God of the gap argument?

    Not at all. Artifacts are facts: they can be observed, and most of them can be directly observed today (a watch, a car, a computer, and so on).

    They do not need divine intervention. And yet they exhibit tons of original functional information.

    How can that be? The answer is simple enough: they just need human intervention.

    But it does not stop there. Why are humans capable of doing something that known laws, alone, cannot do?

    A little reasoning can easily bring us to the credible theory that some specific human experiences, in particular the ability to have the conscious experiences of understanding and purpose, allow humans to design objects with such huge content in functional information.

    So, a reasonable theory to explain the similar pattern of functional information in biological beings is: some agent capable of understanding and purpose designed them.

    Again, no gaps at all: only simple scientific reasoning.

    Again, no divine intervention invoked.

    The problem arises after, as soon as we ask ourselves: OK, but who is, or are, these agents capable of understanding and purpose who supposedly designed biological beings?

    Humans are not really feasible for that.

    So, I think that everyone can choose, at that point, and say:

    a) I cannot believe that other agents may exist who are capable of understanding and purpose, and who were in a condition of being able to design biological beings. However, the problem of biological information remains an observed fact without any reasonable explanation, indeed a mystery. I have faith that some day we can find some explanation for it, without having to recur to designers.

    b) I can believe that other agents may exist who are capable of understanding and purpose, and who were in a condition of being able to design biological beings. Some form of divine intervention is for me a possible, but not necessarily the only, alternative. However, I do believe that the problem of functional information will never be explained without recurring to some form of design, and therefore of conscious intervention. Of course, I am always ready to consider any credible explanation of the non design type, if and when it will be provided.

    OK, I believe that both positions can be respected. I respect a), even if my convinced position is b).

    What is not so respectable is the obstinacy in considering scientifically sound an explanation (the neo-darwinian paradigm) which can already be considered false.

    This is how I see things. As everybody can see, there is no space for the concept of “gaps” in this reasoning, unless we want to consider a “gap” any observed fact that needs explanation and that we cannot yet explain. If so, not only science, but I would say the whole human cognition, is built upon gaps.

  223. 223
    gpuccio says:

    Dionisio:

    “Isn’t the intelligent design (ID) paradigm based on what is known instead of the unknown?”

    Exactly. that’s the essence of my verbose intervention at #222. 🙂

  224. 224
    Mung says:

    Again, no gaps at all, of any kind, here.

    If there are no gaps, there is no reason for any jumps. 🙂

  225. 225
    gpuccio says:

    Mung:

    You can jump as a sport, not only to overcome gaps! 🙂

  226. 226
    Dionisio says:

    SATB1 & SATB2 related papers:

    Referenced in the OP:

    Here is a very brief recent bibliography:

    Essential Roles of SATB1 in Specifying T Lymphocyte Subsets

    SATB1 overexpression correlates with gastrointestinal neoplasms invasion and metastasis: a meta-analysis for Chinese population

    SATB1-mediated Functional Packaging of Chromatin into Loops

    Here is a brief recent bibliography about SATB2:

    Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex

    SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer

    Genes & Development 2009

    Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression

    http://genesdev.cshlp.org/content/23/22/2625

    AJMG 2016:

    SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations

    http://onlinelibrary.wiley.com.....38022/full

    eLIFE 2016:

    Satb2 determines miRNA expression and long-term memory in the adult central nervous system

    https://elifesciences.org/articles/17361

    Development 2017:

    The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo

    http://dev.biologists.org/content/144/8/1450

    Springer 2017:

    Satb2 Ablation Impairs Hippocampus-Based Long-Term Spatial Memory and Short-Term Working Memory and Immediate Early Genes (IEGs)-Mediated Hippocampal Synaptic Plasticity

    https://link.springer.com/article/10.1007/s12035-017-0531-5

  227. 227
    Dionisio says:

    gpuccio @223:

    Exactly. that’s the essence of my verbose intervention at #222

    Well, the problem is that some interlocutors don’t like to read verbose explanations, no matter how clear those explanations are. Maybe reading comprehension issues?

    Maybe that’s why they like the reductionist bottom-up reverse engineering approach to research, which keeps the scientists constantly surprised by unexpected things?

    🙂

  228. 228
    Dionisio says:

    Off topic. A substantial proportion of the visits to this website come from Spain lately?

    Check this out:

    http://www.ranksays.com/uncommondescent.com

  229. 229
    john_a_designer says:

    gpuccio,

    Above @ 217 I wrote.

    “Typically (and IMO justifiably) Darwinists and other naturalistic evolutionists criticize scientifically minded creationists for invoking the God-of-the-gaps argument to explain the very real gaps in the phylogenetic tree.”

    Let me revise that. Because I don’t know (can’t prove) whether the gaps are real or not, instead of “very real gaps in the phylogenetic tree,” I should have written, “apparent gaps in the phylogenetic tree.” Of course, if there are apparent gaps it’s logically possible it’s because there really are gaps.

    It’s not only creationists and ID’ists who concede there are apparent gaps but evolutionists like Gould and Eldridge have also conceded as much. Gould for example said, “The absence of fossil evidence for intermediary stages between major transitions in organic design, indeed our inability, even in our imagination, to construct functional intermediates in many cases, has been a persistent and nagging problem for gradualistic accounts of evolution.”

    He further conceded that Darwin’s explanation that the fossil record is imperfect “persists as the favored escape of most paleontologists from the embarrassment of a record that seems to show so little of evolution directly.”

    https://evolutionnews.org/2015/01/problem_5_abrup/

    If you believe there are no apparent gaps in the phylogenetic tree prove to me there are not. If you can prove to me that to me then you win the argument game-set-match. But I want scientific proof not simply your belief or opinion.

  230. 230
    Dionisio says:

    john_a_designer @229:

    But I want scientific proof not simply your belief or opinion.

    Sorry to disappoint you, but I doubt you will get any scientific proof of anything from your politely dissenting interlocutors here.

  231. 231
    gpuccio says:

    john_a_designer:

    I am not sure what you mean with “gap”. I usually do not discuss fossils, because I have very limited understanding of that field. So, I stick to molecular functionality, referring to the usually accepted tree considered as a sequence of appearance and connection between phyla, species and so on.

    As I believe in common descent, I believe that species are connected by some continuity, with ample addition of new information due to design.

    So, I don’t know what a gap should be. Of course there is no absolute continuity between species, because each species is different from another, and there is ample difference at the molecular level and informational level. That’s what I call a jump: a rather sudden appearance of new information. That can be explained only by design.

    I would not say that these are gaps any more than I would say that there is a gap between a model of a car and the successive model.

    Of course, even design can be more ore less gradual, but up to know what we can see in the existing proteome seems to point to a rather discontinuous design.

    All another thing is the argument about gaps of knowledge. The God of the gaps, Darwin of the gaps, and so on. I just don’t understand what is meant. More simply, I think that here are things we observe (facts) that we can explain rather well, ad others that we cannot explain. Science is about trying to explain what cannot yet be explained. Doe that make it a science-of-the-gaps?

    I think that I definitely dislike the word: “gap”. I will probably agree with you if we first agree on our definition.

    For example, all my reasoning here is based on the assumption (well supported by facts, and almost universally accepted) that, in the tree of life vertebrates derive from the first chordates, which were not yet vertebrates: those chordates that are today represented by urochordata and cephalochordata.

    Can we say that there is a gap between these first chordates and vertebrates?

    It depends what we mean with “gap”.

    Of course vertebrates are, just from the beginning, very different from their chordate ancestors. My OP here is exactly about that, and my previous OP has shown more than 1.7 millions of bits of new functional information in vertebrates.

    It’s certainly a jump: two different things, the second deriving from the first, but with a lot of innovation, designed innovation.

    But if you want to call it a gap, I would like to ask: what would not be a gap? If two things are different, they are different, even if the second derives from the first. If we must define gap in the sense of a jump that cannot be explained by the neo-darwinian paradigm, I would say that the tree is made only of gaps, and nothing else, because IMO even a jump of a few functional AAs is a real problem for neo-darwinism, and certainly a real impossibility from 30 AAs on (about 120 bits).

    So, in that sense, I would call any species as being a gap in respect to all other species.

    But, if we get rid of the neo-darwinian paradigm, then informational jumps are not gaps, but only signatures of design innovation in a basic continuity that also reuses existing hardware and information.

  232. 232
    Dionisio says:

    gpuccio,

    It seems like words are used very lightly, in such a careless way, that cause confusion.
    The word ‘evolution’ is seen in so many different contexts meaning different things. What happens after fertilization is a developmental evolution. But that’s not the same as the bacteria turning antibiotic-resistant.
    The same disregard for exact meaning is seen with the word ‘gap’ as you well explained.
    The term ‘jump’ that you have used to refer to the sudden appearance of new complex functional information in proteins seems very appropriate and clear.

  233. 233
    Dionisio says:

    We show that systemic dysregulation of CRGs is also found in prostate cancer, including a 4-gene signature (HBEGF, HOXC13, IGFBP2, and SATB1) capable of differentiating recurrent from non-recurrent prostate cancer.

    A four gene signature predictive of recurrent prostate cancer
    Justin Komisarof, Matthew McCall, Laurel Newman, Wiam Bshara, James L. Mohler, Carl Morrison, Hartmut Land
    Oncotarget, 2017, Vol. 8, (No. 2), pp: 3430-3440
    http://www.impactjournals.com/oncotarget/

    Overexpression of SATB1 Is Associated with Biologic Behavior in Human Renal Cell Carcinoma

    http://journals.plos.org/ploso.....ne.0097406

    ——-

    Prognostic significance of SATB1 in gastrointestinal cancer: a meta-analysis and literature review

    http://www.impactjournals.com/.....B%5D=16867

    ——-

    Decreased SATB2 expression is associated with metastasis and poor prognosis in human clear cell renal cell carcinoma

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466939/pdf/ijcep0008-3710.pdf

  234. 234
    gpuccio says:

    Dioniso:

    Yes, it seems that I have disturbed a couple of VIPs (very important proteins) here!

    Next time, I will try to be more careful. 🙂

  235. 235
    Dionisio says:

    gpuccio:

    There is a large number of papers on SATB1 and SATB2.
    It’s difficult to see them all.
    Many papers on those two proteins deal with the deleterious effect of any problems with their regulation and expression.
    You definitely touched a very sensitive area of the proteome.

    Now, look at this:
    Google SATB1 SATB2
    and see how many pages of search results you get in return. I see 14 pages.
    Notice at the end of the 4th page your latest OP (this thread)!!!
    O boy, what have you done? 🙂
    OK, confess publicly right here that you knew this would happen, didn’t you? 🙂

  236. 236
    Dionisio says:

    gpuccio:

    Bing SATB1 SATB2

    returns different results.

    On the 5th page this appears:

    Evolution News and Views on Dawkins dumped from Berkeley …
    uncommondescent.com

    4 days ago
    https://uncommondescent.com/intelligent-design/interesting-proteins-dna-binding-proteins-satb1-and-satb2/#comment-636372. 37. MatSpirit July 24, 2017 at 11:14 am.

    That’s pointing to a link at the end of my comment @36 in another thread:

    https://uncommondescent.com/intelligent-design/evolution-news-and-views-on-dawkins-dumped-from-berkeley-did-it-serve-him-right/#comment-636381

    Then later on page 16 of the search results I see this:

    Uncommon Descent | Serving The Intelligent Design Community
    kin.tv

    Interesting proteins: DNA-binding proteins SATB1 and SATB2. July 14, 2017: Posted by gpuccio under Intelligent Design: 9 Comments.

    Yes, definitely you’ve disturbed a couple of VIPs
    🙂

  237. 237
    Dionisio says:

    gpuccio:

    Does this relate to the topic of sudden appearance of functional information in proteins?

    A glimpse into the specialization history of the lipases/acyltransferases family of CpLIP2

    Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics
    Volume 1865, Issue 9, September 2017, Pages 1105-1113
    https://doi.org/10.1016/j.bbapap.2017.06.004

    http://www.sciencedirect.com/s.....3917301255

    There is more here:

    https://www.scopus.com/results/citedbyresults.uri?sort=plf-f&cite=2-s2.0-77955584075&src=s&imp=t&sid=9a23a7d92603c0c6151eda7d36cddffc&sot=cite&sdt=a&sl=0&origin=inward&editSaveSearch=&txGid=6b3ad6f761091807a7c0138bb2888bf4

  238. 238
    Mung says:

    Please don’t denature the proteins!

  239. 239
    bill cole says:

    gpuccio

    Very nice post. I would second Mung’s interest in proteins unique to the eye.
    This is an area that looks like it is very hard for the darwinian mechanism to explain. Mung did a masterful job at TSZ in challenging a new evolution book. The author paid a visit to defend his work.

    I have come up with a definition for Common descent called orthodox common descent. These are the evolutionary biologists that make the claim that animal life is connected by cell division and reproduction alone.

    I would consider you a reform common descent supporter because you allow a potentially Devine foot in the door called design. I join you in this group. I think Mike Behe and Mung also are part of this group.

  240. 240
    Mung says:

    I don’t know. I don’t want to overload our good friend gpuccio.

    Most vertebrates have a single type of chromophore, but five groups of opsin proteins exist: rhodopsin (RH1) and RH1-like (RH2) which are maximally activated by light in the blue-green part of the spectrum … short-wavelength-sensitive opsin-1 (SWS1), which is maximally activated by violate-blue wavelengths … short-wavelength-sensitive opsin-2 (SWS2), which is maximally activated by ultra-violate wavelengths … and a long-wavelength- to medium-wavelength-sensitive opsin (LWS/MWS), which is maximally activated by green-red wavelengths …

    – Convergent Evolution: Limited Forms Most Beautiful (p. 179)

    Oh, and “there are only a limited number of sites within opsin that can be altered without producing a non-functional pigment.” (p. 182)

    Perhaps Doug Axe should have chosen opsins, lol.

  241. 241
    ET says:

    So blind and mindless processes can produce tunable proteins for various light wavelengths? Is that really the argument? How pathetically gullible are evolutionists?

  242. 242
    gpuccio says:

    Mung:

    Of the five opsins mentioned at #240, only three are present in humans (RH2 and SWS2 have been lost, as evident also in the Figure about opsin gain and loss at the genomewiki link.

    Of those three, two are proteins with a big jump in vertebrates, as I have already pointed out in my post #182:

    a) Rhodopsin (P08100). 348 AAs.

    Jump from non vertebrates to vertebrates:

    1.091954 bits per aminoacid site

    380 bits

    288 identities; 321 positives

    b) Long-wave-sensitive opsin 1 (P04000). 364 AAs.

    Jump from non vertebrates to vertebrates:

    0.8901099 bits per aminoacid site

    324 bits

    The third one, SWS1, has a different curve, with low homology in sharks, and a big jump in bony fish and amphibians, lost in crocodiles, conserved in further species. Again, that can already be seen in the figure at genomewiki.

  243. 243
    Mung says:

    ET @ 241: I don’t know. Let’s ask some.

    rvb8, how pathetically gullible are you?

  244. 244
    gpuccio says:

    bill cole:

    “Very nice post.”

    Thank you! 🙂

    “I would second Mung’s interest in proteins unique to the eye.”

    I am doing what I can.

    “This is an area that looks like it is very hard for the darwinian mechanism to explain.”

    Absolutely!

    “Mung did a masterful job at TSZ in challenging a new evolution book. The author paid a visit to defend his work.”

    I am sure Mung was brilliant. I can feel some pity for the author.

    “I have come up with a definition for Common descent called orthodox common descent. These are the evolutionary biologists that make the claim that animal life is connected by cell division and reproduction alone.

    I would consider you a reform common descent supporter because you allow a potentially Divine foot in the door called design. I join you in this group. I think Mike Behe and Mung also are part of this group.”

    Very good definitions. You are absolutely on target. However, for consistency with my position, I would not use the term “Divine foot”, and would just stick to a “design foot”. 🙂

  245. 245
    gpuccio says:

    Mung:

    Can you suggest a metrics? 🙂

  246. 246
    gpuccio says:

    Dionisio at #237:

    Yes, but that seems more about smaller jumps, about “tweaking” of function in a protein family, at least if we judge from the abstract:

    “Using Ancestral Sequence Reconstruction, we have generated a putative ancestral lipases/acyltransferases, PaleoLAc. This enzyme shares a high level of identity with CpLIP2 but has a different catalytic behavior.”

    (emphasis mine).

    Unfortunately, I cannot access the full article to have more details.

    Tweaking an existing function in a protein family, with limited AA changes, is indeed a “grey zone”. Axe has shown that even in that kind of scenario neo-darwinian evolution is not a satisfying explanation, but as there is no shortage at all of much more extreme situations, as we have seen, I would stick to them for the moment.

  247. 247
    bill cole says:

    gpuccio

    The third one, SWS1, has a different curve, with low homology in sharks, and a big jump in bony fish and amphibians, lost in crocodiles, conserved in further species. Again, that can already be seen in the figure at genomewiki.

    Genes being lost and then coming back seems to be a big problem for orthodox common descent. Thoughts?

  248. 248
    gpuccio says:

    bill cole:

    I have no definitive answer to that. Probably some genes are “lost” in some branches because their specific function is not necessary in that branch, or it is simply performed by some alternative pathway.

    The “coming back” could maybe be explained because the original gene was passed before it became lost in that specific branch.

    The important thing, IMO, is to acknowledge that loss of genes is not a rare thing, but it is certainly not the rule. In most cases, the natural history of a protein is rather linear.

    Of course, some information can be lost in specific species, rather than in whole big branches, but that has really no special relevance for the general scenario.

  249. 249
    Mung says:

    Can you suggest a metrics?

    Similarly gullible people must be closely related.

  250. 250
    Dionisio says:

    gpuccio @246:

    “there is no shortage at all of much more extreme situations”

    Agree. The couple of VIPs you just disturbed in this thread are a clear example.

  251. 251
    gpuccio says:

    Mung:

    More on our two opsins (Rhodopsin and Long-wave-sensitive opsin 1).

    The scenario here is similar to what we have observed for SATB1 and SATB2.

    Let’s see why.

    Each of the two proteins is extremely conserved from shark to humans, and exhibits a big jump in vertebrates (IOW, most of the conserved information is generated in sharks).

    Rhodopsin (348 AAs):

    Total homology between shark (Scyliorhinus canicula) and humans:

    608 bits; 288 identities; 321 positives

    Jump in vertebrates:

    380 bits; 165 identities

    b) Long-wave-sensitive opsin (364 AAs)

    Total homology between shark (Callorhincus milii) and humans:

    573 bits; 264 identities; 305 positives

    Jump in vertebrates:

    324 bits; 118 identities

    So, there is no doubt that the two molecules are extremely conserved (83% and 73% identity between sharks and humans).

    There is also no doubt that both exhibit a very big informational jump at the beginning of vertebrate history (380 + 324 bits).

    Now, let’s compare the two human molecules:

    Rhodopsin and LWS opsin in humans share:

    281 bits; 149 identities; 211 positives

    Now, if we consider that the two molecules share a very similar basic identity with the opsins present in non vertebrates, we can see that the best hit in deuterostomia non vertebrates is:

    228 bits and 126 identities for Rhodopsin

    249 bits and 146 identities for LWS opsin

    So, we can say that the two molecules, in humans, share essentially the basic structure and sequence of opsins that were already present in non vertebrates, but are completely different for the part of information which is specific to vertebrates.

    And, if we compare the two corresponding molecules in sharks (Rhodopsin and Red-sensitive opsin-like protein), again we find a similar result:

    275 bits; 142 identities; 217 positives

    incredibly similar to what we had found comparing the two human molecules:

    281 bits; 149 identities; 211 positives

    This is not a case. Of course, the basic structure and sequence of opsins is based on pre-vertebrate information which is shared by the two molecules in the same way in sharks and humans. IOWs, it is basic information that is conserved from non vertebrate deuterostomia to sharks and humans.

    But the rest is all another thing.

    Each of the two molecules has more than 300 bits of new information which:

    a) appears for the first time in vertebrates

    b) is conserved between sharks and humans, but

    c) is different in each of the two molecules.

    It’s the same scenario that we have seen for SATB1 and SATB2, and that is evidence that the two proteins of my OP are no rare exception.

    It’s also important to note that these opsins are extremely functionally constrained. For example, 83% of the sequence is identical between sharks and humans, a result that is certainly not common. We can say, therefore, that almost all the sequence of the molecule is functional, an idea that certainly will not make our darwinist friends happy, considering how they like to think that only a very small part of the sequence of proteins is really specific!

    So, Mung, you are, as usual right:

    “Perhaps Doug Axe should have chosen opsins” 🙂

  252. 252
    Mung says:

    Thanks gpuccio. I am going to have to learn how to do this kind of research myself. Perhaps you should hand out homework assignments. hah!

  253. 253
    RodW says:

    OK, well is there any point in posting here now? If so direct me to some posts and I’ll weigh in

  254. 254
    gpuccio says:

    RodW:

    You could look at wd400 arguments in post #133 and at my answers in posts #144, 149, 157, 159, 171 and 213.

  255. 255
    RodW says:

    gpuccio

    Ok, I’m working my way through them.

    #144. You suggest that both ID and evolution are based on alternate interpretation of the facts. I don’t think this could be the case. Its not like the evidence from fossils, anatomy, molecular bio, genetics etc could point to either ID or Evo and its a kind of glass-is-half-empty/full choice that we all make based on our preference. The evidence must clearly be on one side.
    To follow up on what WD40 said I’d say that when one looks very superficially, ID and Evo might seem compatible, and arguments about ‘common design’ might seem reasonable, but when one looks in detail that’s not the case.
    YEC say that Noah’s flood explains the pattern of the fossil record. But if you know anything at all about the fossil record you can see that’s absurd.

  256. 256
    gpuccio says:

    RodW:

    I am not sure that I understand your comments at #255.

    Of course ID and neo-darwinian theory are alternative explanations of facts: the facts involved being of course the functional information we see in biological beings, and the problem of how to explain its origin.

    “Alternative” means that they cannot be both true. Either biological information evolved through RV and NS, or it was designed. So, I certainly agree with you: the evidence must clearly be on one side.

    And I have no doubts on what side it is! 🙂

    You say:

    “To follow up on what WD40 said I’d say that when one looks very superficially, ID and Evo might seem compatible, and arguments about ‘common design’ might seem reasonable, but when one looks in detail that’s not the case.”

    I have never thought that ID and neo-darwinian evolution are compatible. So, it seems that I agree with you, and you with me.

    “and arguments about ‘common design’ might seem reasonable,”

    I have never, never made arguments about “commone design”. If you read well my OP and my posts, you will see that my argument is about common descent through design.

    I don’t believe that common design can really explain what we observe in biological information. I have defended that idea many times. I think that common descent cannot be reasonably denied, with what we know. My main argument about that is the evidence from progressive divergence of Ks (IOWs, the rather regular rate of neutral variation in neutral sites). I have debated a lot, here, with others IDists who do not accept common descent.

    But I certainly don’t believe that common descent and RV + NS can explain the appearance of complex functional information. I believe that ID theory proves that only common descent + design can explain it.

    Finally, you say:

    “YEC say that Noah’s flood explains the pattern of the fossil record. But if you know anything at all about the fossil record you can see that’s absurd.”

    I agree. And so? What has that to do with ID?

  257. 257
    RodW says:

    gpuccio #149

    Well, for a new gene to arise from a non coding sequence, at least two things must take place:
    a) Transcription of the sequence must take place
    b) An ORF must be acquired, so that the transcribed sequence may be translated and become a gene
    Nobody knows exactly in what order the two things may happen, in the limited understanding that we have today of the issue. One hypothesis is that the non coding sequence is already transcribed, then acquires an ORF and is translated. Another hypothesis is that many ORFs exist but are not transcribed (“cryptic ORFs”), and at some point one of them is transcribed.

    a) Transcription is already happening in 80% of the genome, even non-functional parts. One of the papers in the refs for the second paper ( by Tautz) calculates how long before every region is covered by transcription.
    b) No. An ORF is any sequence that doesn’t contain a STOP codon. A random sequence of DNA will have a length distribution of ORFS around an average ( IIRC ~150 bases). SO the genome contains lots of them. Very long ORFs are relatively rare and the fact that de novo genes tend to be much shorter than older genes is supporting evidence for their existence.

    Whatever. In both cases, one thing is for certain: unless and until the sequence is both transcribed and translated, no form of NS can take place for its function as a protein sequence, because no protein exists.

    Yes. Translation could occur from the first MET in the RNA or from many other aa at low efficiency.

    IOWs, if a new gene emerges from a non coding sequence, whatever the modality, its “evolution” is completely neutral up to the moment it is both transcribed and translated. IOWs, up to the moment it becomes a new gene.

    Yes. Its luck that produces the RNA and protein. Presumably this happens often over evolutionary time but the vast majority have no function. When one by chance does have a function NS acts on it to change the sequence relatively fast. This is what the evidence shows.

    That means that the emergence of a new gene, in the absence of any design intervention, is left purely to random variation. NS can have no role at all.

    Right, NS begins with the emergence of a new protein that has some level of function. NS improves that function.

    Of course, darwinists imagine that after the emergence of the new gene, NS comes to the rescue, and operates its miracles. OK, faith has no limits. But remember, all the classic reasonings of neo-darwinism:
    a) Gradual evolution of function
    b) Recombination
    c) Starting near a functional island, and profiting of imaginary connections between functional islands
    and so on, here do not apply.

    No, see above

    Here we are starting from a completely random non coding sequence, according to the neo-darwinist theory. Until it becomes transcribed and translated, there is no reason at all that it may have any information about any protein sequence. None at all.

    No. All DNA sequences potentially code for protein.

    So, the imagined NS should operate on a completely random sequence, when the sequence is already transcribed and translated. Not good for the neo-darwinian scenario. Not good at all.

    Just about everything in living things evolve from slight modifications of previous things. De novo genes shocked most scientists. 10 years ago I would have said its absolutely impossible.

    Just a few final remarks:

    2) The second paper I quoted above seems to demonstrate that new genes, when they emerge, already have specific properties that “normal” non coding DNA does not have. IOWs, the long preparation of the sequence through apparently neutral variation, before any possible intervention of NS, seems to generate specific functional properties before the sequence is translated into a protein. How do you think that can happen?

    There was no ‘preparation’ of the sequence. Randome sequences that are transcribed and translated can occasionally produce functional proteins.

    3) So much for the idea that non coding DNA is junk: it is a source of new genes, the clue to all functional evolution.

    No one ever thought that non-coding = junk. In the 1950s scientists knew about regulatory sites. But there is nonfunctional DNA that can give rise to new genes. This is what the 2 papers you posted, and the references therein, show.

    To summarize: because RNA polymerase initiates transcription by a stochastic mechanism there will always be a large amount of non-functional transcription. Those transcripts will occasionally produce proteins at a low rate and some small fraction of those will by luck have selectable function. All of this has already been demonstrated. ( I’m pretty sure nonfunctional peptides have been detected)
    The evidence that they produce functional proteins is that the de novo genes have non-functional counterparts in closely related species. They are much shorter than the average protein (ORFs tend to be short) and they have a higher than neutral mutation rate of the type that indicates positive selection. And most important…. they contain mostly intrinsically disordered regions. In other words they don’t contain the folded domains that we find in most older proteins. This last point should ring a bell with everyone here, and not just because of gpuccio’s post on SATB. Doug Axe’s entire argument is that protein domains can’t evolve at random and protein domains are required for function. But de novo genes show that domains ARE NOT required for function. Not only that but they show that the stability of de novo genes can gradually improve by natural selection (although I don’t know if anyone has suggested that new domains have formed)
    Even YEC’s agree that NS can improve the function of biological entities. The difficulty in appreciating and accepting evolution for everyone ( IDers AND scientists) has always been how to you get the new structure, new body part, new protein etc from scratch? This topic, and the papers gpuccio has posted show that its much easier to get functional proteins from scratch – without the need for intelligent intervention- than anyone had imagined.

  258. 258
    gpuccio says:

    RodW:

    We agree on some things, but you misunderstand others.

    “Transcription is already happening in 80% of the genome, even non-functional parts.”

    I never said anything different, Transcription happens, as ENCODE teaches. That it is functional ot not, is all to be decided. However, transcription ofo non coding DNA is usually non translated.

    My point is that a new gene must be both transcribed and translated.

    “No. An ORF is any sequence that doesn’t contain a STOP codon…”

    The prevailing theories about the origin of new genes are two, as I say in my post: either a cryptic existing ORF becomes transcribed and translated, or some non coding sequence acquires an ORF by mutation. You seem to privilege the first scenario, but evidence exists also for the second. Of course, both things could happen.

    “Yes. Its luck that produces the RNA and protein. Presumably this happens often over evolutionary time but the vast majority have no function. When one by chance does have a function NS acts on it to change the sequence relatively fast. This is what the evidence shows.”

    No. If you look at one of the papers I reference, it shows that new genes have specific properties just from the beginning of their appearance, and that cannot be explained by NS. So, that’s not what the evidence shows.

    “Right, NS begins with the emergence of a new protein that has some level of function. NS improves that function.”

    What evidence have you that most new genes are random sequences, and that some instead have som naturally selectable function?

    Not much is known about the function of new genes. In no way it has been shown that some basic function emerges randomly with reasonable probability and can lead by NS to a new complex function in a new protein.

    “No, see above”

    No what? You agreed that NS cannot act until a naturally selectable function emerges. My point is that none of the classic imagined neo-darwinian concepts:

    a) Gradual evolution of function
    b) Recombination
    c) Starting near a functional island, and profiting of imaginary connections between functional islands
    and so on, here do not apply.

    can apply to the emergence of new genes from non coding DNA. If they apply. they apply only after and if a naturally selected function appears, by mere chance. Do you agree on that?

    I said:

    Here we are starting from a completely random non coding sequence, according to the neo-darwinist theory. Until it becomes transcribed and translated, there is no reason at all that it may have any information about any protein sequence. None at all.

    You comment:

    “No. All DNA sequences potentially code for protein.”

    You don’t understand my point. If a non coding DNA sequence becomes suddenly translated, while it was never translated before (IOWs, a new gene), there is no specific information in the DNA sequence about any protein function. IOWs, the codons that emerge as the new translation of a sequence that had never coded for a protein cannot of course have any special relationship with protein space. IOWs, they cannot be the result of any process of:

    a) Gradual evolution of function
    b) Recombination
    c) Starting near a functional island, and profiting of imaginary connections between functional islands
    and so on, here do not apply.

    As I said before. Instead, those processes have been usually invoked for the emergence of new genes form gene duplication, because in that case the original sequence that undergoes transformation was a protein coding sequence. In that sense, origin form non coding DNA is a much worse scenario than origin from gene duplication, from a neo-darwinian point of view (even if some different specific problems arise also in the gene duplication scenario).

    Do you understand my point now?

    “Just about everything in living things evolve from slight modifications of previous things. De novo genes shocked most scientists. 10 years ago I would have said its absolutely impossible.”

    It is still impossible, without design. You have just become acquainted with the idea.

    “There was no ‘preparation’ of the sequence. Randome sequences that are transcribed and translated can occasionally produce functional proteins.”

    No, again you did not read well what I wrote. I will repeat it:

    The second paper I quoted above seems to demonstrate that new genes, when they emerge, already have specific properties that “normal” non coding DNA does not have. IOWs, the long preparation of the sequence through apparently neutral variation, before any possible intervention of NS, seems to generate specific functional properties before the sequence is translated into a protein. How do you think that can happen?

    That paper finds those specific properties in the vast majority of new genes. Those properties are not found in non coding DNA. So, obviously, there is a preparation through mutations before the new genes emerge, and NS can have no role in that. How do you explain it?

    Moreover, if the scenario you suggest were true, cells should be repleted of non functional, random new genes, out of which only once in a while (if ever) a functional, naturally selectable gene could emerge. But that is not the case, of course.

    “To summarize: because RNA polymerase initiates transcription by a stochastic mechanism there will always be a large amount of non-functional transcription. Those transcripts will occasionally produce proteins at a low rate and some small fraction of those will by luck have selectable function. All of this has already been demonstrated. ( I’m pretty sure nonfunctional peptides have been detected)”

    You are sure of too many things. None of that has been “demonstrated”. Of course there is a lot of transcription that is not destined to translation, but that was not at all expected, it was shown by encode and by the new powerful molecular techniques in the last years.

    That a large amount of non translated transcription is non functional is at the center of scientific debate. It is not demonstrated at all, indeed there is growing evidence that non translated transcription is essential for almost all cell functions.

    “Those transcripts will occasionally produce proteins at a low rate and some small fraction of those will by luck have selectable function.”

    Demonstrated? Where?

    “I’m pretty sure nonfunctional peptides have been detected”

    It’s very difficult to demonstrate that something is not functional. I can agree that non functional peptides can exist, but then? What has that to do with all our discussions here?

    “The evidence that they produce functional proteins is that the de novo genes have non-functional counterparts in closely related species.”

    In the papers I have read, they have non translated counterparts, not non functional counterparts. That has been shown in primates. Can you give examples of what you say?

    “They are much shorter than the average protein”

    That is true.

    “and they have a higher than neutral mutation rate of the type that indicates positive selection.”

    Examples, please?

    “And most important…. they contain mostly intrinsically disordered regions. In other words they don’t contain the folded domains that we find in most older proteins.”

    That new genes are different, for some aspects, from older genes is true. I don’t see how that helps your theory, however.

    “In other words they don’t contain the folded domains that we find in most older proteins.”

    That is not necessarily true, even if it can be true in part. The fact that we don’t recognize domains in new genes is in part because new genes are categorized as such exactly because they don’t have recognizable homologies. I am not sure that we have enough structural information about new genes to exclude that they contain folded parts which could be, in the future, recognized as new domains.

    “Doug Axe’s entire argument is that protein domains can’t evolve at random and protein domains are required for function.”

    I cannot speak for Axe, but I think that his point it that functional domains cannot evolve at random. Which is true. That protein domains are required for many functions is certainly true, but it is certainly not true that only domains have function. We have the example of intrinsically disordered proteins (the old ones, not new genes) that are functional, and all my reasoning in this OP is about the idea that interdomain sequences are functional. It was you, if I remember well, who said differently.

    Moreover, my point is that even new genes, with or without domains, if they are functional, cannot arise at random. Unfortunately, not much is known about the functions of new genes. I think we have to wait some more time to understand better.

    Another important point is that the emergence of new domains has certainly been slowing down in the course of natural history. Almost half of existing superfamilies were already present in LUCA. Does that mean that no new information has been generated, say, between chimp and humans? Of course not. The simple fact is, most new information in the most “recent” part of natural history is probably regulatory, and I believe that we still don’t understand it.

    “Not only that but they show that the stability of de novo genes can gradually improve by natural selection”

    Examples, please. It is really strange to invoke NS for genes whose function we don’t know.

    “Even YEC’s agree that NS can improve the function of biological entities. ”

    Well, I don’t agree. Certainly, not generating new complex functional information. The few examples of NS we know are about very trivial tracts. But maybe I cannot understand your point because I am not an YEC. 🙂

    “This topic, and the papers gpuccio has posted show that its much easier to get functional proteins from scratch – without the need for intelligent intervention- than anyone had imagined.”

    ???????

    No comment!

  259. 259
    Dionisio says:

    Perhaps the comment @255 could serve as an illustration of what the term “incoherence” stands for.

    🙂

  260. 260
    Mung says:

    My dear gpuccio,

    You just don’t understand how evolution works. I’ll explain it to you once I figure it out.

  261. 261
    Mung says:

    RodW:

    All DNA sequences potentially code for protein.

    Like the footprints in the sand of birds on the beach can potentially produce a love poem. 🙂

  262. 262
    Dionisio says:

    gpuccio:

    When you are ready to take a break from the “heated” discussions you’re having here, you might want to take a look at this:

    https://uncommondescent.com/intelligent-design/neuroscience-tries-to-be-physics-asks-is-matter-conscious/#comment-636746

  263. 263
    ET says:

    RodW:

    Yes. Its luck that produces the RNA and protein. Presumably this happens often over evolutionary time but the vast majority have no function. When one by chance does have a function NS acts on it to change the sequence relatively fast. This is what the evidence shows.

    What evidence shows that? The following paper pretty much squashes that scenario: Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution:

    For population sizes and mutation rates appropriate for Drosophila, a pair of mutations can switch off one transcription factor binding site and activate another on a timescale of several million years, even when we make the conservative assumption that the second mutation is neutral.

    And that is just for binding sites!

  264. 264
    Dionisio says:

    ET,

    Sorry to disappoint you with this news, but no matter how hard you may try, some folks won’t understand what you mean, apparently because they simply don’t want to.

  265. 265
    ET says:

    Dionsio- I understand what RodW is saying and he is being honest, at least. Evolutionism does demand that chance occurrences, ie luck, produces the DNA, RNA and proteins (he forget the DNA) and that unless the organism(s) are less fit during the build-up then natural selection will preserve whatever is there. It’s just that the sheer amount of luck involved makes it not only inconceivable but also as close to impossible something can get. Even Richard Dawkins admits that science can allow for only so much luck. What he fails to realize is that his position has nothing but luck.

  266. 266
    Dionisio says:

    ET,

    What he fails to realize is that his position has nothing but luck.

    OK, but why does he fail to realize that?
    Is it because it’s too difficult to understand?
    Or because it hasn’t been explained well?
    Or a language issue?

  267. 267
    Dionisio says:

    gpuccio @251:

    Very interesting comment on the proteins Rhodopsin and Long-wave-sensitive opsin 1. Thanks.

    BTW, are they also in the VIP club along with SATB1 and SATB2?

    🙂

  268. 268
    Dionisio says:

    gpuccio,

    @256 you mentioned ‘common design’.
    What is that in biology?

  269. 269
    Dionisio says:

    gpuccio @251:

    On page 6 & 7 in the paper referenced through the link @262 they talk about rhodopsin proteins within the context of quantum physics.

  270. 270
    gpuccio says:

    ET:

    “For population sizes and mutation rates appropriate for Drosophila, a pair of mutations can switch off one transcription factor binding site and activate another on a timescale of several million years, even when we make the conservative assumption that the second mutation is neutral.”

    Thank you for the interesting article.

    But, of course, there is no difficulty for RV + NS, in the RodW version, to generate 731 specific AA sites and 1300+ bits of functional information, with population size and mutation rate and generation time of the first chordates (whatever they were), on a timescale of, at most, 30 million years (but probably much less).

    And, definitely, I am not making the conservative assumption that any relevant part of those mutations can be neutral.

    You say:

    “I understand what RodW is saying and he is being honest, at least.”

    I agree. And he is not condescending like wd400, at least (well, not too much!) 🙂

  271. 271
    gpuccio says:

    Dionisio:

    Common design would be the theory that functional similarities can be explained by functional constraints, and do not imply common descent. IOWs, the designer designs it from scratch each time, but has to use the same solutions because they are the required solutions, or the best.

    That can work in theory, but it cannot explain the observed differences between similar proteins, and their rather regular relationship with evolutionary time distance.

    I refer in particular to the divergence of synonimous sites, measured by the Ks, that remain IMO the best (not the only) argument for physical common descent.

    Moreover, I must say that explaining all sequence similarities in proteins by functional constraints, even when a short evolutionary time separates the species (see for example chimps and humans) seem a little far-fetched.

  272. 272
    Dionisio says:

    gpuccio’s discussion with RodW seems interesting. RodW should get credits for that too. 🙂

    Note how gpuccio dissects the text and comments on separate parts making sure nothing is left out. Not many folks have such a detail-oriented commenting style here -as far as I see. It would help if others could take note and try to imitate such an exegetical approach.

  273. 273
    Dionisio says:

    gpuccio @258:

    “…either a cryptic existing ORF becomes transcribed and translated…”

    In such a case, isn’t the information already present* in the cryptic existing ORF before it becomes a gene?

    (*) or stored in or associated with

  274. 274
    Dionisio says:

    gpuccio @270:

    But, of course, there is no difficulty for RV + NS, in the RodW version, to generate 731 specific AA sites and 1300+ bits of functional information, with population size and mutation rate and generation time of the first chordates (whatever they were), on a timescale of, at most, 30 million years (but probably much less).

    Well, perhaps with some imagination one could accept such an scenario, wouldn’t you? 🙂
    See Harry Potter is widely accepted out there. 🙂
    I personally prefer Cinderella’s story, where a pumpking turns into an elegant carriage, mice become beautiful horses and a grasshopper is hired as their cochero. At least those things make sense, don’t they?

    🙂

  275. 275
    Dionisio says:

    gpuccio @271:

    “That can work in theory, but it cannot explain the observed differences between similar proteins, and they rather regular relationship with evolutionary time distance.

    Assuming it’s “their” instead of “they”, are the observed differences between similar proteins the result of accumulated mutations through biological history? Are those differences functional or just structural?

    Does “common design” relate to the name of this website?
    Or that’s a separate issue?

    All the years working on a software development project for engineering design applications and lately trying to understand how the biological systems function have not left much spare time to look at this part of the discussion on how we got the biological systems to begin with.
    I’ve been looking at the terminology often seen here: uncommon/common descent, etc, with a “huh?”, but kind of letting it go by, thinking that I could come back to clarify it later.
    Perhaps it’s time for me to start looking into this too. 🙂

  276. 276
    Dionisio says:

    gpuccio,

    The main discussion in this thread is about the origin of the functional information seen in proteins, right?

    Once we get through this discussion (if one can) and have all the required proteins in place, we still have to answer how they are recruited and used in signaling pathways and regulatory networks (both genetic and epigenetic). Is this correct?

  277. 277
    Dionisio says:

    gpuccio @271:

    […] explaining all sequence similarities in proteins by functional constraints […]

    another way to explain it is by those similarities being carried over from previous proteins that pass those segments along through biological history?

  278. 278
    gpuccio says:

    Dionisio:

    The issue of new genes is still not well understood, I believe. So, anything we say is still tentative (personally, I don’t share RodW easy certainties). 🙂

    From what we know, it seems that the information in the new gene as we observe it was already, at least in good part, present in the pre-protein sequence, be it a non coding sequence or a cryptic ORF.

    The problem is that we don’t know much of the functions of these new genes. I suppose they are probably regulatory, and that makes even more difficult understanding them.

    So, as we don’t know exactly what they do, it’s even more difficult to understand if the function is already present at the origin of the translated protein, of if it changes after, least of all by what mechanisms.

    The simple fact that these genes, arising at least in part from non coding genes, have properties very different from non coding genes at large (like intrinsic disorder, see the paper I discussed above with RodW), is very interesting, and makes us wonder how these specific properties were acquired through variations in the non coding sequence, where NS has no role.

    Again, design is the best answer..

  279. 279
    gpuccio says:

    Dionisio:

    “are the observed differences between similar proteins the result of accumulated mutations through biological history? Are those differences functional or just structural?”

    The differences in non synonymous site, IOWs those that cause an AA change, are measured by Ka, and can be both:

    a) functional (the protein is tweaked differently in different species)

    or

    b) neutral variations accumulated through biological history.

    It is not easy to distinguish the two, but I think there is evidence enough that both occur.

    On the other hand, the differences in synonymous site, IOWs those that so not cause an AA change, are measured by Ks, and are considered neutral, at least in most cases (there is some evidence that in some cases synonymous mutations can cause functional variations, for example by influencing the translation rate of the protein).

    In most proteins, Ka/Ks is significantly lower than 1, because non synonymous mutations are antagonized by negative (purifying) selection, when the sites where they occur are functionally constrained.

    The important point is that Ks, which is not under significant functional constraint, is grossly proportional to the evolutionary chronological separation between species. That confirms that the divergence in synonymous site is due to neutral mutations, and that it is passed from species to species physically.

    Which is, IMO, the best argument for common descent, because the similarities can be explained, with some difficulty, by common design, the differences in non synonymous sites could still be explained, with greater difficulty, by common design, arguing that all of them are functionally motivated (which is, IMO, far-fetched).

    But the differences in synonymous sites, and their diverging pattern in time, cannot, as far as I can understand, be reasonably explained by common design. They very strongly argue for common descent.

  280. 280
    gpuccio says:

    Dionisio:

    As far as I know, the name of this blog, “Uncommon descent”, was created by Dembski, the founder of the blog itself.

    I think that Dembski does not accept common descent, but I doubt that this is a relevant part, or even a part at all, of his ID arguments. His reasons to refuse CD are more probably theological.

    Other important ID proponents, like Behe, do accept CD. Personally, I have never had any doubts, even if I try to keep an open mind. Let’s say that my conviction that biological information is designed is much, much scientifically stronger than my conviction of CD.

    Which is, however, rather solid.

  281. 281
    gpuccio says:

    Dionisio:

    “another way to explain it is by those similarities being carried over from previous proteins that pass those segments along through biological history?”

    Yes. That’s exactly my point of view. The similarities are passed “passively”, and so are the new accumulated differences due to neutral variation.

    Instead, all new complex functional information is added by design.

  282. 282
    gpuccio says:

    Dionisio:

    “Once we get through this discussion (if one can) and have all the required proteins in place, we still have to answer how they are recruited and used in signaling pathways and regulatory networks (both genetic and epigenetic). Is this correct?”

    Yes. Absolutely.

  283. 283
    Dionisio says:

    gpuccio:

    Thank you for the comments @278-282.

    Have a good weekend.

  284. 284
  285. 285
    es58 says:

    Gpuccio. Since you are usually so thorough as to label all your responses by post number I may have missed it if you had responded to wd400 at posts 177,187,188
    . If not would appreciate your feedback to them. thanks!

  286. 286
    gpuccio says:

    es58:

    I have commented on some points of post #177 in my post #186 (to Origenes).

    #187 was not addressed to me. I have not commented post #188.

    Consider that wd400 was not very clear about his goodwill to participate in a direct discussion, and when he posted these I still had to complete my answers to his old post that, although short, summarized some very important general objections.

    However, later today I will review these three posts that you mention, and I will try to address aspects that may not have been discussed yet.

  287. 287
  288. 288
    gpuccio says:

    wd400’s post #177:

    I have already discussed some points in my post #186.

    Other points that deserve discussion:

    Doesn’t take much googling to find places where I’ve tried to explained the relevance of phylogeny and the limitations of taking BLAST databases as complete records of diversity

    BLAST databases are the main objective information we have on protein evolution. If we don’t recur to them for our inferences, to what should we recur? Unless we accept the neo-darwinian idea that facts are not necessary! 🙂

    Moreover, there is no need that the existing proteomes be a “complete” record of diversity. They are certainly a very significant sample of diversity. Even if parts of diversity have certainly been lost, there is no reason to expect a systematic loss limited to all the information that could support the neo-darwinian theory (for example, the traces of all the necessary functionally selectable intermediates).

    The question of finding (or, actually inferring) ancestral intermediates is a strange one. First, such intermediates obviously exist, bacause the proteins are not 100% conserved, allowing us to infer ancestral states.

    Now, let’s try to understand this tricky point as clearly as possible.

    I have never denied protein descent. Indeed, it’s the foundation of my argument.

    What I deny is that huge new amount of functional information can be added to proteins, in the course of evolutionary descent, without a design intervention.

    Let’s consider, for example, the opsins we have debated here after Mung introduced them as a good example of what we are considering.

    Let’s say tow rather different opsins, both present in humans:

    1) Rhodopsin, that we have already considered

    2) Melanopsin

    Well, they certainly share some minor but relevant part of the sequence:

    140 bits, 86 identities, 155 positives.

    The expect value is 4e-42, highly significant.

    Who can deny that the two proteins are connected in some way? I certainly have no intention to deny it.

    So, let’s say that they derived from a common ancestor protein, well before the appearance of vertebrates. And they still retain the signature of that common origin. 140 bits of functional information, conserved for hundreds of millions of years.

    And we could certainly, with some approximation, infer some ancestral state for that common ancestral protein.

    And so?

    The point is:

    1) Rhodopsin has in humans huge homology with the shark protein, as we have seen:

    608 bits; 288 identities; 321 positives

    of which the jump in vertebrates is a very big part:

    380 bits; 165 identities

    2) Melanopsin too has strong homology with shark:

    541 bits; 278 identities; 337 positives

    of which the jump in vertebrates is a very big part:

    219 bits; 133 identities

    The best hit in chordates for those two proteins is:

    1) Rhodopsin:

    Ciona intestinalis: 228 bits

    2) Melanopsin:

    Branchiostoma floridae: 322 bits

    So, in chordates, both proteins show a definite homology with the human form, which is higher than the basic information content conserved in both proteins (what we could call “the conserved ancestral functional information”). So we have:

    1) Rhodopsin:

    Human-conserved ancestral functional information: 140 bits

    Human-conserved functional information in chordates (non vertebrates): 228 bits

    Human-conserved functional information in sharks: 608 bits

    2) Melanopsin:

    Human-conserved ancestral functional information: 140 bits

    Human-conserved functional information in chordates (non vertebrates): 322 bits

    Human-conserved functional information in sharks: 541 bits

    So, I ask:

    What’s the relevance of the fact that “proteins are not 100% conserved, allowing us to infer ancestral states” to our discussion here?

    Absolutely none.

    The relevant fact is that the ancestral protein underwent at least two accumulations if functional information: a minor one before vertebrates, which generates some functional information specific for each of the two proteins, and different from the basic shared sequence:

    about 88 bits in Rhodopsin

    about 182 bits in Melanopsin

    But the second accumulation is the bigger jump:

    about 280 bits in Rhodopsin

    about 219 bits in Melanopsin

    It must be clear that, as the jump grows, the credibility of a gradual generation of the functional sequence by RV + NS goes down from infinitesimal to infinitely infinitesimal.

    If you look only at those amino acids are conserved then ask for the intermediates then obviously we won’t find them.

    I really don’t understand wd400’s point here. That would make sense if we were observing minimal differences, say two or three AA jumps, which are still in the range of what RV and NS can do (maybe) in millions of years.

    But here we are looking at jumps of hundreds of conserved AAs. And it is not obvious at all that we don’t find any intermediates.

    IOIWs, we could well observe proteins that change in small steps, and grow in functionality in small steps. That would be much more compatible with the neo-darwinian theory.

    What we really observe, instead, is a true and strong falsification of that theory.

    It’s obvious, instead, that I must look at “those amino acids that are conserved”, because those are the AAs that are certainly functional.

    It is also strange to ask think discontinuous jumps between clades is a problem and not a prediction of evolution down a tree.

    A prediction? Are we kidding?

    Ah, OK, I forgot. Neo-darwinism predicts all and the contrary of all.

    All vertebrates share ~30 million years of evolutionary history

    Yes, and so? I would say 30 millions at most, probably much less.

    variation that occured in that time are not available for study when we look at modern organisms

    Again with modern organisms! We are looking at old sequences conserved in modern organisms. A lot of clues are available for study by looking at them. Those that are not available, are probably not available because they never existed, especially if the lack of specific clues is universal, all pervading and systematic.

    The idea that not finding homologies for all domains in non- (not pre!) vertebrate animals using blastp and default settings is evidence that these domains were not present in the ancestors of vertebrates is also strange. These domains are all present in modern non-vertebrates.

    Again, I am not speaking of domains, but of specific, conserved sequences. I have recognized all the domains that can be identified, according to NCBI, in the proteins I have discussed. But my analysis is about sequences. And I have also separately analyzed sequence conservation both in domains and in inter-domain sequences.

    What is really strange is this obstinate refusal to consider the evidence from sequences. Sequences are the place where digital information is stored. They are the object of variation. Variation is variation of sequence. The search space is the sequence search space. Domains are a meta-construct. RV knows nothing about domains and structures. It is just a variation of sequence.

    The only possible reason for this obstinacy in ignoring the importance of sequences is that what they say is not good at all for the neo-darwinist paradigm.

    More in next post.

  289. 289
    Mung says:

    Moreover, there is no need that the existing proteomes be a “complete” record of diversity.

    Haha. The fossil record is complete enough for Darwinists to make leaps of inference, but the protein databases are not?

    Now THAT is FUNNY!

  290. 290
    gpuccio says:

    Mung:

    That’s the point:

    We are a minority.

    We are an extreme minority.

    We are a despised minority.

    But we have a lot of fun! 🙂

  291. 291
    RodW says:

    gpuccio,

    Actually polls show you in the majority and you’re certainly not despised. ( well maybe Mung is 🙂 )

    Anyway. I cant post during the weekend so is there anything for me to respond to?

    BTW my real is Rod Wilson. I’d be curious to hear everyone’s real name. I have difficulty relating to screennames.

  292. 292
    gpuccio says:

    RodW:

    “Actually polls show you in the majority and you’re certainly not despised.”

    Please, don’t destroy my few illusions!

    My name is Giuseppe Puccio, if that can help.

    I have addressed some of your points at #258.

    I would also appreciate if you could comment on the important problem I discussed in my posts #129 and 157 and 201, about the (impossible) deconstruction of complex functions into simpler steps.

  293. 293
    Mung says:

    well maybe Mung is

    LoL. maybe

  294. 294
    gpuccio says:

    Mung:

    You are always the fortunate! 🙂

  295. 295
  296. 296
    es58 says:

    WD400, RodW or anyone else:

    I would appreciate a response to GPuccios posts at:
    #186 and #288 which respond to WD400’s post at #177.
    Thanks!

    Gpuccio:
    At your post #288 you had said you intended to post more. I don’t know if that was more related to the post at #177 or to some other post, but, either way, it would be appreciated. Thanks!

    All: The link I posted at #295 is an interesting article by a neuroscientist who has found a sea creature with a different nervous system than any known animal. It has no seratonin, no dopamine, etc. It apparently has a completely different set of proteins(?)

  297. 297
    RodW says:

    es58

    Ok, here I think is the relevant part.

    I have never denied protein descent. Indeed, it’s the foundation of my argument.
    What I deny is that huge new amount of functional information can be added to proteins, in the course of evolutionary descent, without a design intervention.

    And here are some examples of his calculations:

    Let’s say tow rather different opsins, both present in humans:
    1) Rhodopsin, that we have already considered
    2) Melanopsin
    Well, they certainly share some minor but relevant part of the sequence:
    140 bits, 86 identities, 155 positives.

    ……

    Rhodopsin has in humans huge homology with the shark protein, as we have seen:
    608 bits; 288 identities; 321 positives

    I assume the first number is the ‘functional information’ he is saying has appeared in the protein. Am I correct? How does he calculate this? ( I’d ask him but I don’t know if he’s still checking here)

  298. 298
    gpuccio says:

    RodW:

    For the two opsins, the functional information that appears at the vertebrate jump is:

    380 bits for Rhodopsin

    219 bits for Melanopsin

    How do I calculate those numbers?

    It’s simple.

    Look at this:

    1) Rhodopsin:

    Human-conserved ancestral functional information: 140 bits

    Human-conserved functional information in chordates (non vertebrates): 228 bits

    Human-conserved functional information in sharks: 608 bits

    2) Melanopsin:

    Human-conserved ancestral functional information: 140 bits

    Human-conserved functional information in chordates (non vertebrates): 322 bits

    Human-conserved functional information in sharks: 541 bits

    So, the new information that appears in vertebrates and is conserved up to humans is:

    For Rhodopsin: 608 – 228 = 380 bits

    For Melanopsin: 541 – 322 = 219 bits

    IOWs, I subtract from the total human conserved information present in sharks the human conserved information present in chordates non vertebrates.

    I thought that was clear: it is the same methodology I have used in the OP, and which shows that, for STAB proteins, the new functional information appearing in vertebrates is:

    For SATB1: 1049 bits (1203 – 154)

    For SATB2: 1072 bits (1197 – 125)

    Is that clear?

  299. 299
    gpuccio says:

    es58:

    Yes, I meant to add some further comment about wd400’s posts.

    But frankly, I don’t know if I will find the time, because I will be away for about three weeks, starting this saturday, and I will not be able to post in that time.

    Before leaving, I will try to post something more, if I can. And I will certainly post a greeting to all those who have discussed in this thread. 🙂

    When I am back, I will certainly check the thread. Let’s see is there is still something to say.

  300. 300
    gpuccio says:

    es58:

    By the way, I had seen the OP about ctenophores. Fascinating and amazing.

    OK, the article is not a scientific paper, not at all, but still:

    “‘It was much more than just the presence or absence of just a few genes,’ he says. ‘It was really a grand design.’”

    Moroz now counts nine to 12 independent evolutionary origins of the nervous system – including at least one in cnidaria (the group that includes jellyfish and anemones), three in echinoderms (the group that includes sea stars, sea lilies, urchins and sand dollars), one in arthropods (the group that includes insects, spiders and crustaceans), one in molluscs (the group that includes clams, snails, squid and octopuses), one in vertebrates – and now, at least one in ctenophores.”

    “What’s fascinating is how these different pathways of evolution arrived at nervous systems that look so similar across the animal tree of life. Take for example the work of Nicholas Strausfeld, a neuro-anatomist at the University of Arizona in Tucson. He and others have found that the neural circuits underlying smell, episodic memory, spatial navigation, behaviour choice and vision in insects are nearly identical to those performing the same functions in mammals – despite the fact that different, though overlapping, sets of genes were harnessed to build each one.”

    “These similarities reflect two key principles of evolution, factors that are probably important on any world where life has emerged. The first is convergence: these far-flung branches of the evolutionary tree arrived at common designs for a nervous system because they each had to solve the same fundamental problems.”

    Emphasis mine.

  301. 301
    gpuccio says:

    es58:

    So, neo-darwinian evolution is such a powerful algorithm that it can easily build a nervous system 12 times independently! What’s the problem?

    It can obviously solve fundamental problems. Strangely, it solves them always in the same way (at the general design level), but using different building blocks. No surprise, neo-darwinian evolution has very clear ideas about the result to be obtained, and it pragmatically uses what it can find to obtain it!

    Neo-darwinian evolution is really a grand design, after all. 🙂

    And, I suppose, the same is true for flight, which arose independently I don’t know how many times.

    Why be surprised? A nervous system and flight are piece of cake! Just solve the rights problems, and there they are!

  302. 302
    gpuccio says:

    es58:

    For example, I have always been fascinated by stationary flight. From Wikipedia:

    “Hovering is stationary flight, exhibited by bees, dragonflies, hummingbird hawk-moths, hummingbirds, bats, helicopters, balloons, and kites. Hovering generally consumes large amounts of fuel when done by rockets, special airplanes or hummingbirds.”

    I am sure that neo-darwinian evolution can easily explain, by some kind of convergence, the evolution of stationary flight in bees, hummingbirds and kites! 🙂

  303. 303
    es58 says:

    RodW: Please see gpuccio’s response to your request for clarification at post #298; thanks in advance for your reply!

    gpuccio: “I will be away for about three weeks”; Knowing it’s summer I assumed you might already be away. I hope it’s for a pleasure trip. Thanks again for all your feedback.

  304. 304
    gpuccio says:

    Well, I just wanted to thank all those who have contributed to the very good discussion here, beginning with our kind “antagonists”, RodW and wd400, and of course all the friends who have given support and contributed their ideas.

    As I said, I will not be able to post for about three weeks. I am sure that the discussion will go on, either here or elsewhere.

    A good summer to all! 🙂

  305. 305
    Dionisio says:

    gpuccio,

    Your insightful posts have been very instructive as usual.
    They definitely present a very strong case supporting ID.
    Well done! Thanks!
    Enjoy the summer and please come back with more posts.

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