Intelligent Design

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

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As a follow-up to my previous post:

The highly engineered transition to vertebrates: an example of functional information analysis

I am presenting here some results obtained by a general application, expanded to the whole human proteome, of the procedure already introduced in that post.

Main assumptions.

The aim of the procedure is to measure a well defined equivalent of functional information in proteins: the information that is conserved throughout long evolutionary times, in a well specified evolutionary line.

The simple assumption is that  such information, which is not modified by neutral variation in a time span of hundreds of million years, is certainly highly functionally constrained, and is therefore a very good empirical approximation of the value of functional information in a protein.

In particular, I will use the proteins in the human proteome as “probes” to measure the information that is conserved from different evolutionary timepoints.

The assumption here is very simple. Let’s say that the line that includes humans (let’s call it A) splits from some different line (let’s call it B) at some evolutionary timepoint T. Then, the homology that we observe in a protein when we compare organisms derived from B  and humans (derived from A) must have survived neutral variation throughout the timespan from T to now. If the timespan is long enough, we can very safely assume that the measured homology is a measure of some specific functional information conserved from the time of the split to now.

Procedure.

I downloaded a list of the basic human proteome (in FASTA form). In particular, I downloaded it from UNIPROT selecting all human reviewed sequences, for a total of 20171 sequences. That is a good approximation of the basic human  proteome as known at present.

I used NCBI’s blast tool in local form to blast the whole human proteome against known protein sequences from specific groups of organisms, using the nr (non redundant) NCBI database of protein sequences, and selecting, for each human protein, the alignment with the highest homology bitscore from that group of organisms.

Homology values:

I have used two different measures of homology for each protein alignment:

  1. The total bitscore from the BLAST alignment (from now on: “bits”)
  2. The ratio of the total bitscore to the length in aminoacids of the human protein, that I have called “bits per aminoacid” (from now on, “baa”). This is a measure of the mean “density” of functional information in that protein, which corrects for the protein length.

The values of homology in bits have a very wide range of variation  in each specific comparison with a group of organisms. For example, in the comparison between human proteins and the proteins in cartilaginous fish, the range of bit homology per protein is 21.6 – 34368, with a mean of 541.4 and a median of 376 bits.

The vlaues of homology in baa , instead, are necessarily confined between 0 and about 2.2. 2.2, indeed, is (approximately) the highest homology bitscore (per aminoacid) that we get when we blast a protein against itself (total identity).  I use the BLAST bitscore because it is a widely used and accepted way to measure homology and to derive probabilities from it (the E values).

So, for example, in the same human – cartilaginous fish comparison, the range of the baa values is:  0.012 – 2.126, with a mean of 0.95 and a median of 0.97 baas.

For each comparison, a small number of proteins (usually about 1-2%) did not result in any significant alignment, and were not included in the specific analysis for that comparison.

Organism categories and split times:

The analysis includes the following groups of organisms:

  • Cnidaria
  • Cephalopoda (as a representative sample of Mollusca, and more in general Protostomia: cephalopoda and more generally Mollusca, are, among Protostomia, a group with highest homology to deuterostomia, and therefore can be a good sample to evaluate conservation from the protostomia – deuterostomia split).
  • Deuterostomia (excluding vertebrates): this includes echinoderms, hemichordates and chordates (excluding vertebrates).
  • Cartilaginous fish
  • Bony fish
  • Amphibians
  • Crocodylia, including crocodiles and alligators (as a representative sample of reptiles, excluding birds. Here again, crocodylia have usually the highest homology with human proteins among reptiles, together maybe with turtles).
  • Marsupials (an infraclass of mammals representing Metatheria, a clade which split early enough from the human lineage)
  • Afrotheria, including elephants and other groups (representing a group of mammals relatively distant from the human lineage, in the Eutheria clade)

There are reasons for these choices, but I will not discuss them in detail for the moment. The main purpose is always to detect the functional information (in form of homology) that was present at specific split times, and has been therefore conserved in both lines after the split. In a couple of cases (Protostomia, Reptiles), I have used a smaller group (Cephalopoda, Crocodylia) which could reasonably represent the wider group, because using very big groups of sequences (like all protostomia, for example) was too time consuming for my resources.

So what are the split times we are considering? This is a very difficult question, because split times are not well known, and very often you can get very different values for them from different sources. Moreover, I am not at all an expert of these issues.

So, the best I can do is to give here some reasonable proposal, from what I have found, but I am completely open to any suggestions to improve my judgements. In each split, humans derive from the second line:

  • Cnidaria – Bilateria. Let’s say at least 555 My ago.
  • Protostomia – deuterostomia.  Let’s say about 530 My ago.
  • Pre-vertebrate deuterostomia (including chordates like cephalocordata and Tunicates) – Vertebrates  (Cartilaginous fish). Let’s say 440 My ago.
  • Cartilaginous fish – Bony fish. Let’s say about 410 My ago.
  • Bony fish – Tetrapods (Amphibians). Let’s say 370 My ago, more or less.
  • Amphibians – Amniota (Sauropsida, Crocodylia): about 340 My ago
  • Sauropsida (Crocodylia) – Synapsida (Metatheria, Marsupialia): about 310 My ago
  • Metatheria – Eutheria (Afrotheria): about 150 My ago
  • Atlantogenata (Afrotheria) – Boreoeutheria: probably about 100 My ago.

The simple rule is: for each split, the second member of each split is the line to humans, and the human conserved information present in the first member of each couple must have been conserved in both lines at least from the time of the split to present day.

So, for example, the human-conserved information in Cnidaria has been conserved for at least 555 MY, the human-conserved information in Crocodylia has been conserved for at least 310 My, and so on.

The problem of redundancy (repeated information).

However, there is an important problem that requires attention. Not all the information in the human proteome is unique, in the sense of “present only once”. Many sequences, especially domains, are repeated many times, in more or less similar way, in many different proteins. Let’s call this “the problem of redundancy”.

So, all the results that we obtain about homologies of the human proteome to some other organism or group of organisms should be corrected for that factor, if we want to draw conclusions about the real amount of new functional information in a transition. Of course, repeated information will inflate the apparent amount of new functional information.

Therefore, I computed a “coefficient of correction for redundancy” for each protein in the human proteome. For the moment, for the sake of simplicity, I will not go into the details of that computation, but I am ready to discuss it in depth if anyone is interested.

The interesting result is that the mean coefficient of correction is, according to my computations, 0.497. IOWs, we can say that about half of the potential information present in the human proteome can be considered unique, while about half can be considered as repeated information. This correction takes into account, for each protein in the human proteome, the number of proteins in the human proteome that have significant homologies to that protein and their mean homology.

So, when I give the results “corrected for redundancy” what I mean is that the homology values for each protein have been corrected multiplying them for the coefficient of that specific protein. Of course, in general, the results will be approximately halved.

Results

Table 1 shows the means of the values of total homology (bitscore) with human proteins in bits and in bits per aminoacid for the various groups of organisms.

 

Group of organisms Homology bitscore

(mean)

Total homology

bitscore

Bits per aminoacid

(mean)

Cnidaria 276.9 5465491 0.543
Cephalopoda 275.6 5324040 0.530
Deuterostomia (non vertebrates) 357.6 7041769 0.671
Cartilaginous fish 541.4 10773387 0.949
Bony fish 601.5 11853443 1.064
Amphibians 630.4 12479403 1.107
Crocodylia 706.2 13910052 1.217
Marsupialia 777.5 15515530 1.354
Afrotheria 936.2 18751656 1.629
Maximum possible value (for identity) 24905793 2.2

 

Figure 1 shows a plot of the mean bits-per-aminoacid score in the various groups of organisms, according to the mentioned approximate times of split.

Figure 2 shows a plot of the density distribution of human-conserved functional information in the various groups of organisms.

 

 

 

The jump to vertebrates.

Now, let’s see how big are the informational jumps for each split, always in relation to human conserved information.

The following table sums up the size of each jump:

 

 

 

 

Split Homology bitscore jump (mean) Total homology bitscore jump Bits per aminoacid (mean)
Homology bits in Cnidaria 5465491 0.54
Cnidaria – Bilateria (cephalopoda) -6.3 -121252 -0.02
Protostomia (Cephalopoda)- Deuterostomia 87.9 1685550 0.15
Deuterostomia (non vert.) – Vertebrates (Cartilaginous fish) 189.6 3708977 0.29
Cartilaginous fish-Bony fish 54.9 1073964 0.11
Bony fish-Tetrapoda (Amphibians) 31.9 624344 0.05
Amphibians-Amniota (Crocodylia) 73.3 1430963 0.11
Sauropsida (Crocodylia)-Synapsida (Marsupialia) 80.8 1585361 0.15
Metatheria (Marsupialia) – Eutheria (Afrotheria) 162.2 3226932 0.28
Total bits of homology in Afrotheria 18751656 1.63
Total bits of maximum information in  humans 24905793 2.20

 

The same jumps are shown graphically in Figure 3:

 

As everyone can see, each of these splits, except the first one (Cnidaria-Bilateria) is characterized by a very relevant informational jumps in terms of human-conserved information. The split is in general of the order of 0.5 – 1.5 million bits.

However, two splits are characterized by a much bigger jump: the prevertebrate-vertebrate split reaches 3.7 million bits, while the Methateria-Eutheria split is very near, with 3.2 million bits.

For the moment I will discuss only the prevertebrate-vertebrate jump.

This is where a great part of the functional information present in humans seems to have been generated: 3.7 million bits, and about 0.29 bits per aminoacid of new functional information.

Let’s see that jump also in terms of information density, looking again at Figure 2, but only with the first 4 groups of organisms:

 

Where is the jump here?

 

We can see that the density distribution is almost identical for Cnidaria and Cephalopoda. Deuterostomia (non vertebrates) have a definite gain in human-conserved information, as we know, it is about 1.68 million bits, and it corresponds to the grey area (and, obviously, to the lower peak of low-homology proteins).

But the real big jump is in vertebrates (cartilaginous fish). The pink area and the lower peak in the low homology zone correspond to the amazing acquisition of about 3.7 million bits of human-conserved functional information.

That means that a significant percentage of proteins in cartilaginous fish had a high homology, higher than 1 bit per aminoacid, with the corresponding human protein. Indeed, that is true for 9574 proteins out of 19898, 48.12% of the proteome. For comparison, these high homology proteins are “only” 4459 out of 19689,  22.65% of the proteome in pre-vertebrates.

So, in the transition from pre-vertebrates to vertebrates, the following amazing events took place:

  • About 3,7 million bits of human-conserved functional information were generated
  • A mean increase of about 190 bits per proteins of that information took place
  • The number of high human homology proteins more than doubled

Correcting for redundancy

However, we must still correct for redundancy if we want to know how much really new functional information was generated in the transition to vertebrates. As I have explained, we should expect that about half of the total information can be considered unique information.

Making the correction for each single protein, the final result is that the total number of new unique functional bits that appear for the first time in the transition to vertebrates, and are then conserved up to humans, is:

1,764,427  bits

IOWs, more than 1.7 million bits of unique new human-conserved functional information are generated in the proteome with the transition to vertebrates.

But what does 1.7 million bits really mean?

I would like to remind that we are dealing with exponential values here. A functional complexity of 1.7 million bits means a probability (in a random search) of:

1:2^1.7 million

A quite amazing number indeed!

Just remember that Dembski’s Universal Probability Bound is 500 bits, a complexity of 2^500. Our number (2^1764427) is so much bigger that the UPB seems almost a joke, in comparison.

Moreover, this huge modification in the proteome seems to be strongly constrained and definitely necessary for the new vertebrate bodily system, so much so that it is conserved for hundreds of millions of years after its appearance.

Well, that is enough for the moment. The analysis tools I have presented here can be used for many other interesting purposes, for example to compare the evolutionary history of proteins or groups of proteins. But that will probably be the object of further posts.

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

  1. 1
    Origenes says:

    GPuccio:

    The simple assumption is that such information, which is not modified by neutral variation in a time span of hundreds of million years, is certainly highly functionally constrained, and is therefore a very good empirical approximation of the value of functional information in a protein.

    If we are justified in accepting GPuccio’s assumption, then the rest of his argument follows like clockwork. Given his assumption, functional information is being measured and functional information jumps* are shown to exist, which cannot possibly be explained by Darwinian processes.

    IOWs Darwinism is dead and GPuccio has provided us with the most convincing ID argument yet.

    Is it so simple?

    Well, I don’t see how Darwinians can object to GPuccio’s assumption. I really don’t.

    – – –
    (*)Let’s not even contemplate the massive (and matching) epigenetic change that accompanies these DNA information jumps …

  2. 2
    gpuccio says:

    Origenes:

    Thank you for the comment.

    Yes, of course this analysis is only about the proteome, and does not consider the non coding DNA, even the most obvious functional parts of it, like promoterome and enhancerome, and all the rest, and epigenetics, and so on…

  3. 3
    Dionisio says:

    Glad to see a new article by gpuccio here!!!
    As usual, very insightful, well researched and solidly documented.
    Definitely it provides much food for thoughts.
    I may have a few questions after I read it carefully.

    Our number (2^1764427) is so much bigger that the UPB seems almost a joke, in comparison.

    This is serious stuff indeed.

  4. 4
    gpuccio says:

    Dionisio:

    You are welcome! 🙂

  5. 5

    Hi GP,

    Congratulations on another excellent paper.

    I expect you may get caught up in cross-platform comments with TSZ, as you did in your last paper.

    If and when time permits, I’d be interested in knowing how you see your paper compare and contrast with Swamidass’s recent paper. Perhaps a comparison doesn’t bear any fruit, but I thought I’d ask.

    Again, congrats.

  6. 6
    gpuccio says:

    UB:

    Thank you. I will have a look at the paper you quote, and let you know.

    (By the means, I have also looked at the other paper you referenced in the other thread, but have not yet had the time to comment on it. I will do that as soon as possible! 🙂 )

    Thank you again!

  7. 7
    gpuccio says:

    UB:

    Just gave a first look at the paper, which seems targeted to criticize the Durston paper (a little late on that, I would say! 🙂 )

    I will comment better on it tomorrow, but just look at Figure 1, which is about the results of their simulation, which is central to the thesis of the paper. I quote from the paper:

    The mutation rates in the simulation correspond to very long time periods. One mutation per amino acid corresponds to more than 30 million years of mammalian evolution (at approximately ten mutations per base per billion years).

    Emphasis mine.

    Well, in their simulation 30 million years reduce the observed homology to about 0.8 baa. We should also note that the unit of measure they are using is Durston’s, which ranges from 0 to 4.5 bits, and corresponds to the total informational potential of a sequence.

    The unit of measure I used here is derived from the BLAST bitscore, which ranges from 0 to about 2.2 baa. That about half of the full informational potential of a sequence, and that’s because the blast algorithm computes the bitscore by making important adjustments, so that it better corresponds to the probability of observing the alignment, given the conditions of the comparison.

    That means that 30 million years, using the blast bitscore, would reduce any homology to about 0.4 baa.

    In my analysis of vertebrates, I find a mean homology (from the bitscore) of 0.9491001 baa (median 0.9685318, range 0.01232162 – 2.12605) between cartilaginous fish and humans, with an evolutionary separation of about 410 million years!

    According to Swamidass’ simulation, how much should it be, after 410 million years of neutral evolution?

    Swamidass gives the answer himself:

    MISA does go to zero if the mutation rate is increased to several events per amino acid, as the memory of the ancestral sequence is wiped. So, in addition to the effect of functional constraints, MISA encodes the mutational age of the protein family.

    (MISA = mutual information of a sequence alignment, in the Swamidass paper)

    Correct. So, if one mutational event per aminoacid reduces the observed homology, in his simulation, to 0.8 baa (corresponding to 0.4 baa in bitscore units), we can be sure that 410 million years of evolution, more than ten times that evolutionary distance, will correspond to more than 10 events per aminoacid, and completely erase any passive homology due to derivation from a common ancestor.

    IOWs, all the homology observed between distant evolutionary lines can be traced to high functional constraints. Which is exactly my point here.

    Another demonstration of the same principle is that 300 – 400 million years of neutral evolution are usually more than enough to erase any detectable homology in the synonymous sites of a protein coding gene, as I have argued many times in my past posts.

    Of course, if we look at shorter evolutionary separations, the effects of passive homology must be taken in consideration. That’s why I have focused here on the transition to vertebrates, which guarantees a long and safe evolutionary separation between the two lines. And, as you can easily see, My general reasonings and data presented here stop at about 100 million years of evolutionary separation, which should anyway ensure that most, maybe not all, of the observed homology is due to functional constraints. If I had discussed the information jump in mammals, for example, I would have mentioned this point, as I will certainly do when I treat that other aspect of my data.

    I think I should thank prof. Swamidass for the kind (but completely unintentional) support! 🙂

  8. 8

    This is why we ask questions!!

    Thanks GP(!) — much to think about.

  9. 9
    Dionisio says:

    gpuccio @7:

    I think I should thank prof. Swamidass for the kind (but completely unintentional) support!

    Does that mean that professor S agrees on “The amazing level of engineering in the transition to the vertebrate proteome”?

    Cool! The guy finally got it! 🙂

    BTW, let’s keep in mind what gpuccio wrote @2:

    […] this analysis is only about the proteome, and does not consider the non coding DNA, even the most obvious functional parts of it, like promoterome and enhancerome, and all the rest, and epigenetics, and so on…

    Now, off topic, here’s a funny thing I noticed the spell checker suggested as replacements for the terms promoterome and enhancerome:
    (1) promote Rome
    (2) enhance Rome
    Since the author of the current thread is Italian, could this be a case of conflict of interests? 🙂
    He pretends to write a scientific article but really wants to enhance and promote Rome! 🙂

  10. 10
    gpuccio says:

    Dionisio:

    “Since the author of the current thread is Italian, could this be a case of conflict of interests?”

    Oh! That could really give me a problem with peer review! 🙂

  11. 11
    gpuccio says:

    UB:

    Now, some other thoughts about Swamidass’paper.

    Figure 2 shows how, given a certain dendity of homology in bits per aminoacid, the total homology scales linearly with sequence length. What a surprise, indeed. We are beyond the trivial here.

    Again, we are dealing with the basic simulation. Again, the homology found is only passive homology, and it is really significant only with less than one event (corresponding to 30 million years separation) and, obviously, long sequences.

    Now, it seems really obvious that if they start form a common ancestor, and then make only limited substitutions, they will still find some passive homology. Again, what a surprise!

    Their point seems to be that in Durston’s methodology some component of sequences that are evolutionary too near can overestimate the evaluation of functional complexity, passing passive homology for functional constraints.

    Well, maybe. As I have explained, that has no relevance at all with my personal methodology, where big evolutionary separation ensures that such an effect cannot be present.

    However, if I wanted to defend Durston (that, after all, is not my task) I would say that I can think of many other factors that can cause an underestimate of functional information in his methodology. For example, considering all sequences labeled with some function in very different species will certainly generate great informational noise, and underestimate the true functional constraints, because many of those sequences can have functional differences that tweak the function in each specific context, and with Durston’s methodology all such differences will simply falsely increase the estimate of the non functional part of the sequence.

    However, as I said, it is not my task to defend Durston from Swamidass’criticism. I would only suggest that he makes no attempt to correct Durston’s “errors”, trying to give an alternative reading of functional information, for example excluding sequences that are evolutionary too near. No, like all defenders of darwinism, he is only interested in denying the relevance of the concept of functional information, and so he is happy to criticize a methodology without offering any alternative.

    As already said, however, my methodology takes well into account the problem of passive homology, and is designed to avoid that problem just from the beginning.

  12. 12
    gpuccio says:

    UB:

    Again on that paper. Supplementary arguments are dedicated to explain how natural mutations would give higher permanence of residual homology. Maybe. However, the reasoning remains similar, and only limited events, IOWs limited evolutionary separation, allows the permanence of relevant detectable homology, in the absence of functional constraints.

    Many of these problems are drastically solved if we use the blast bitscore, as I have done, instead of a full bitscore. The blast algorithm already reduces many of those factors of possible false homology. That’s why it is significantly lower than a full homology bitscore.

    Then there is the old argument of different proteins sharing the same function, which is often used to support the myth of an extremely rich and dense functional space.
    Now, we know that similar functions can be implemented by proteins with scarce sequence similarity and structure similarity. But:

    1) This is certainly not the general case
    2) There is no evidence that similar function means the same function. One of the errors of darwinian thought is to trivialize function, and not recognized that similar functions can really be very different in different contexts. As I have always said, many sequence difference can and certainly have functional value. When we assimilate all the differences to neutral variation, we definitely overestimate non functionality, and underestimate functional information.

    Moreover, we know from experiments like the rugged landscape study (Hayashi) that similar functional results, but with very different levels of functionality, can be found in different functional islands of the proteins landscape, each of them practically isolated from the others, so much so that in that famous experiment there was no realistic chance to find the island of the wildtype function by mutation and natural selection.

    IOWs, the existence of different islands that, in different ways and with different efficiency, can implement a similar (but probably not the same) function is evidence against the connected nature of the protein space: not only different functions are isolated islands in the landscape, as demonstrated by the 2000+ protein superfamilies for which no connection of sequence, structure or function can be found; but even similar functions can be implemented by isolated islands of sequence, without any realistic chance of traversing from one to the other.

  13. 13
    Phinehas says:

    You could hear a pin drop. Quick, someone make a theological comment so the usual interlocutors won’t be so intimidated by the scientific content in this thread!

    😛

  14. 14
    gpuccio says:

    UB:

    Another abused and ambiguous argument is that existing proteins are highly optimized. This is really strange, because I think it is really an argument for their high functional information.

    Again, the Hayashi experiment teaches us a lot of things. Not only the wildtype is optimized, but it is so optimized that it is impossible to find it from other functional islands.

    Darwinists like to think of optimization as the result of gradual natural selection in a connected landscape. But that is simply false, and no real examples of complex optimization, implying more than one or two AAs, really exist.

    the truth is that optimization means that we have proteins that represent extremely rare functional islands, and that the existence of those optimized sequences can only be explained by design.

    Moreover, gradual optimization is so often blindly invoked, but as soon as you ask where are the evidences of that gradual optimization, especially in terms of surviving intermediate, the magic of a completely efficient NS that has erased any trace of the process is immediately invoke. By the same people that are ready to invoke errors and scarcely efficient proteins in nature as evidence of the same process.

  15. 15
    bill cole says:

    gpuccio

    However, as I said, it is not my task to defend Durston from Swamidass’criticism. I would only suggest that he makes no attempt to correct Durston’s “errors”, trying to give an alternative reading of functional information, for example excluding sequences that are evolutionary too near. No, like all defenders of darwinism, he is only interested in denying the relevance of the concept of functional information, and so he is happy to criticize a methodology without offering any alternative.

    First, thank you for the very interesting analysis. I had several discussions with Dr Swamisass at TSZ. I think the mistake he made in his initial analysis was that he had a different interpretation of MISA that Kirk did. In the case of Kirk MISA was simply information obtained from sequence comparison of genes from different species. Dr Swamidass”s experiment changed the observed sequences and therefore changed MISA away from Kirks definition.

    In all fairness to Dr Swamidass he introduced his paper as only preliminary thinking.

    From reading your work and Kirk’s paper I still wonder if looking at historic sequences will give us a reliable measure of functional information. I would appreciate your thoughts on this and how you see a path to improving the accuracy of our measurements.

  16. 16
    timothya says:

    Gpuccio:

    “I would like to remind that we are dealing with exponential values here. A functional complexity of 1.7 million bits means a probability (in a random search) of:

    1:2^1.7 million

    A quite amazing number indeed!”

    Biological evolution does not proceed by a “random search”. So what, exactly, is the point of this article?

  17. 17
    gpuccio says:

    UB:

    Then there is this pearl:

    This rationale, however, is flawed because evolution does not sample sequences with
    uniform likelihood. If we accept the definition of FI presented in Equation 1, FI just tells us the proportion of sequences that are functional. If evolution just sampled uniformly from the space of all proteins, it is possible that FI would be a good estimate of evolvability. However, evolution proceeds by sampling around existing protein and DNA sequences, which are substantially enriched for function.

    What does he mean? That functional sequences are confined to a restricted sequence space? This is folly! What abou the completely separated 2000+ protein superfamilies?

    And again:

    Evolvability is better
    estimated by measuring the distance between existing sequences and the closest family of functional proteins. FI, however, tells us nothing about how close the first functional protein of a family was to preexisting sequences without that function

    So, who will tell us something about “how close the first functional protein of a family was to preexisting sequences without that function”? A big problem, to which Axe and others have dedicated years of hard work. But no, the answer is simpler: it’s enough to look at Figure 4, well designed by the authors themselves, and all doubts can be solved!

    We have one strong hint that new functions are close to old functions and abundant,
    and therefore easy to evolve.

    One strong hint?

    The same protein family can often perform several different functions. If functionality were astronomically rare and isolated in sequence
    space, this would be nearly impossible.

    Why? Please note that they are strangely receding at the family level. What about superfamilies? No mention of them, of course.

    But families are groups of proteins that already have great similarity in structure, very often in sequence, and usually also in function. Because function can often be modular. One first step to function is some type of folding. The same folding can support different structures (superfamilies). Proteins in the same family share a lot of functional information already. Still, their final function can be significantly different. For example, it is sometimes enough to modify slightly the active site to change affinity for substrates. But again, we are speaking of tweaking at the level of the active site, when the folding and gross structure of the protein are already of a certain kind.

    No one denies that there are similar proteins that, by a change of 2-5 AAs, can have a different function. Axe has shown that even those small “transitions” are not so easy as one could expect. But anyway, that has nothing to do with the appearance of big bulks of functional information, like in the appearance of a new superfamily, or a new protein.

    Finally, Figure 5 is really irritating. Again a simulation, and again evidence of how cognitive bias can generate false and artificial reasoning. In brief, they define a low level of “function” (artificially), then they “evolve” it artificially by mutation and artificial selection, and, surprise surprise, they get high function (always artificially defined). OK, and so? The pearl is that they use this simulation to affirm that the detection of high functional information in the high function group overestimates the true FI, because the low function group exists! This is not even reasoning.

    Of course, what they define “low function” and what they define “high function” are two very different things. Of course, when we define a function, we must also define its minimum level. Of course, the artificial “simulation” has only the hidden purpose to convince the readers that what they do purposefully (artificially evolve what they want to evolve) is a model of what happens in nature. But that is not true at all.

    Where is the rich landscape of low functions, intermediate functions, and so on, all of them connected at sequence level, that allows the generation of the high function optimized wildtypes that we observe in existing proteomes?

    The answer is easy: except in the imagination and false simulations of darwinist fans, they are nowhere to be seen.

    Oh, but of course all the evidence has been “eaten” by the magic of NS!

    Oh, my goodness!

  18. 18
    gpuccio says:

    timothya:

    Old “objection”.

    Biological evolution (according to darwinists) does proceed by random variation and NS. RV is a random search. The role of NS is easily shown as completely helpless, if the RV part (the random search) cannot generate the bits of functional information that confer the function.

    The point of the article is that it tries to quantify how much new functional information is present in vertebrates at the start of their evolutionary history, compared to what was present immediately before (deuterostomia not vertebrates).

    IOWs, a massive information jump.

    If you think that you can easily explain that jump by RV and NS, I am happy for you. I beg to think differently.

    However, I think that trying to quantify these things should be of interest to anyone involved in the discussion.

  19. 19
    gpuccio says:

    bill cole:

    “From reading your work and Kirk’s paper I still wonder if looking at historic sequences will give us a reliable measure of functional information. I would appreciate your thoughts on this and how you see a path to improving the accuracy of our measurements.”

    My thoughts are simple: yes, it will.

    What we already know about proteomes is more than enough to give a reliable general scenario. If we really want to look at it.

    But there is no doubt that the rapidly evolving knowledge about genomes, proteomes, protein functional space, epigenetics and so on will constantly improve our understanding.

    My absolute certainty is that each advancement in each of these fields will only make the evidence for design, if possible, even greater.

    And most people will go on ignoring that evidence.

    That’s how cognitive bias works, especially if established at such a universal level.

    You say:

    “In all fairness to Dr Swamidass he introduced his paper as only preliminary thinking.”

    OK, that’s fine for me. Let’s say it is bad preliminary thinking.

    Well, he may have some minor points partially right about the Durston methodology, but he has made no attempt to correct it and verify the results. He is ideologically motivated, and looks for any possible way to deny the value of functional information in biology. That cannot be accepted, IMO.

  20. 20
    gpuccio says:

    Phinehas:

    “You could hear a pin drop.”

    Correct.

    But, as you can see, we are trying to make some noise, even by a small amount of provocation. Let’s see what happens…

  21. 21
    bill cole says:

    gpuccio

    Finally, Figure 5 is really irritating. Again a simulation, and again evidence of how cognitive bias can generate false and artificial reasoning. In brief, they define a low level of “function” (artificially), then they “evolve” it artificially by mutation and artificial selection, and, surprise surprise, they get high function (always artificially defined). OK, and so? The peral is that they use tis simulation to affirm that the detection of high functional information in the high function group overestimates the true FI, because the low function group exists! This is not even reasoning.

    This is where they describe FI or functional information as MISA. The reason the information is defined as functional is because the sequence comes from a living organism. Once they change the sequence in any way without a biological experiment to verify function all bets are off. The simulation they are doing is essentially meaningless.

  22. 22
    gpuccio says:

    bill cole:

    “The simulation they are doing is essentially meaningless.”

    I agree. Except for the meaning of propaganda.

  23. 23
    timothya says:

    Gpuccio:

    “The point of the article is that it tries to quantify how much new functional information is present in vertebrates at the start of their evolutionary history, compared to what was present immediately before (deuterostomia not vertebrates).”

    This is incoherent. Vertebrates are deuterostomes. What are you talking about?

  24. 24
    Origenes says:

    Bill Cole: From reading your work and Kirk’s paper I still wonder if looking at historic sequences will give us a reliable measure of functional information.

    To be clear, Bill. Do you envision any wiggle room for Darwinists to not accept GPuccio’s assumption?

    GPuccio:

    The simple assumption is that such information, which is not modified by neutral variation in a time span of hundreds of million years, is certainly highly functionally constrained, and is therefore a very good empirical approximation of the value of functional information in a protein.

  25. 25
    gpuccio says:

    timothya:

    “This is incoherent. Vertebrates are deuterostomes. What are you talking about?”

    What’s the problem with you?

    a) Deuterostomia not vertebrates. As you can read in the OP, this group:
    “includes echinoderms, hemichordates and chordates (excluding vertebrates).”

    b) Vertebrates, in particular cartilaginous fish.

    Those are the two lineages considered in evaluating the transition to the vertebrate proteome, and the relative information jump.

    Vertebrates are deuterostome, but not all deuterostome are vertebrates.

    Is it clear now?

  26. 26
    kairosfocus says:

    GP, I suggest linking that earlier post in the first line of this one. KF

  27. 27
    gpuccio says:

    KF:

    Done! 🙂

  28. 28
    timothya says:

    Gpuccio:

    “a) Deuterostomia not vertebrates. As you can read in the OP, this group:
    “includes echinoderms, hemichordates and chordates (excluding vertebrates).”

    b) Vertebrates, in particular cartilaginous fish.”

    Still incoherent. Vertebrates are chordates. How can they be excluded?

    From Wikipedia:

    “There are three major clades of deuterostomes:

    Chordata (vertebrates and their kin)
    Echinodermata (starfish, sea urchins, sea cucumbers, etc.)
    Hemichordata (acorn worms and graptolites)”

  29. 29
    gpuccio says:

    timothya:

    Uff!

    Chordata not vertebrates are cephalochordata and urochordata.

  30. 30
    timothya says:

    Do you have any evidence of the structure and function of the proteins present at the time that these ancient lifeforms existed? And any evidence to support the contention that the divergence of those lifeforms could not have occurred by evolutionary processes?

    Certainly the analysis of modern proteins might give us some insight into what may have existed at the time, but to try to derive a likelihood measure from the modern proteosome is, well, “zombie science”.

  31. 31
    Armand Jacks says:

    A lot of work obviously went into this. Have you though about drafting this as a research paper and submitting it to a peer reviewed paper?

  32. 32
    gpuccio says:

    timothya:

    What I am analyzing are modern proteins, but as the split between the two lineages happened about 410 million years ago, we can only infer that the homology we observe today was present at that time in the common ancestor of the two lineages. That idea is absolutely derived from some simple assumptions which are at the base itself of darwinism, so I can’t see how any darwinist can deny it.

    And I don’t see any “zombie science” in that.

  33. 33
    gpuccio says:

    Armand Jacks:

    “A lot of work obviously went into this.”

    Yes.

    “Have you though about drafting this as a research paper and submitting it to a peer reviewed paper?”

    Yes. But I prefer it this way.

  34. 34
    Origenes says:

    timothya @30

    Do you have any evidence of the structure and function of the proteins present at the time that these ancient lifeforms existed?

    Do you think that proteins can be extracted from those fossils?

    And any evidence to support the contention that the divergence of those lifeforms could not have occurred by evolutionary processes?

    What part of the ‘information jump’ did you not understand?

    Certainly the analysis of modern proteins might give us some insight into what may have existed at the time, but to try to derive a likelihood measure from the modern proteosome is, well, “zombie science”.

    Are you suggesting that the protein sequences of all these distinct organisms became more and more similar (‘modern’) over time? And are you suggesting that this homology is not due to common descent?

  35. 35
    Dionisio says:

    gpuccio,

    can the information jumps be associated with the Delta(x) shown next?

    Given any case of known evolutionary divergence, it could be described as:
    Dev(d1) = Dev(ca) + Delta(d1)
    Dev(d2) = Dev(ca) + Delta(d2)
    Where
    Dev(x) is the developmental process of any given biological system x
    Delta(x) is the whole set of spatiotemporal procedural differences required to produce Dev(x).
    d1 and d2 are two descendants of their common ancestor (ca).
    Assuming the Dev(x) are well known, what hypothetical Delta(d1) and Delta(d2) could be suggested for the following cases?
    Case 1: d1 = placental mammals; d2 = marsupials;
    Case 2: d1 = placental; d2 = monotreme;
    Case 3: d1 = cats; d2 = dogs; (use LUCA for ca)
    Just point to the literature that explains this in details.
    The explanation must be comprehensive, logically coherent and it must hold water under any kind of thorough examination.

    Are you aware of any fully documented real example that illustrates the above Evo-Devo description?

  36. 36
    gpuccio says:

    Dionisio:

    Wow! That is a question!

    I’ll think about it! 🙂

  37. 37
    Armand Jacks says:

    Gpucio@33, suit yourself, but I think it would be a very good way to receive constructive criticism rather than being sniped at. Submitting to a peer review is a great way to get free advice from experts in the field. Besides, I think that you might be happily surprised at the outcome. As long as you are willing to listen to the reviewers suggestions.

    As well, what software did you use to create the kernel density plots or did you build them from scratch. I ask because you use them as part of my work and I am relying on an excel macro I found in line. It works but it is cumbersome.

  38. 38
    gpuccio says:

    Armand Jacks:

    I use R.

  39. 39

    Wow GP … I am just now stumbling back in, and I find much more to consider.

    Thank You for the extra responses.

  40. 40
    PaV says:

    Upright BiPed:

    I looked quickly at the Swadimass paper. It appears that they are using “non-functional” proteins to make the comparison of sequences (MISA) while searching for FI values.

    Here’s the problem: “non-functional” proteins are regular protein sequences in which a “nonsense mutation” has occurred. This brings about a “stop codon” somewhere in the sequence. The RNA editing process simply discards this “non-functional” strand in vivo.

    So, we’re an amino acid away from a “functional” sequence by definition. Well, the authors say FI is zero–which it is–and then say the ‘distance’ between ‘function’ and ‘non-function’ is very, very narrow; hence, evolution is possible.

    If I’ve understood them rightly, it appears they’re not doing science. I wouldn’t spend any time at all on the paper until they address this issue.

    BTW, I searched for “non-functional” and found three instances. NOWHERE in their ‘article’ do they bother to define what it is, how it comes about, etc.

    So, are they ill-informed and honest, or well-informed and dishonest? I don’t know.

  41. 41
    bill cole says:

    Origenes

    To be clear, Bill. Do you envision any wiggle room for Darwinists to not accept GPuccio’s assumption?

    They are always wiggling 🙂 I think GP’s argument is almost certainly correct. There is always the large functional space argument(sequence space is large but functional space is also large) and I am looking to see how solid Kirks argument is and at this point my understanding needs improving. How are you sure the sequences have explored all the functional space?

    GP makes some great points but I see evolution as being much slower then people think due to DNA repair. The cells seem to be designed to minimize variation or else how would a human under go 1 trillion cell divisions during development and be born successfully.

    So the ultimate proof of design may be that cells are not built to evolve. DNA repair keeps them in a very tight range. Every new genome maybe a custom design. Building life on earth was no easy job 🙂

  42. 42
    Origenes says:

    Bill Cole @41

    They are always wiggling 🙂 I think GP’s argument is almost certainly correct. There is always the large functional space argument (sequence space is large but functional space is also large) …

    I do not see how this has any impact on GPuccio’s argument. His argument is very clear and straightforward. As of yet I do not see any weaknesses and hence no wiggle room.

    GP makes some great points but I see evolution as being much slower then people think due to DNA repair.

    In that case you will be very impressed by those massive information jumps.

  43. 43
    bill cole says:

    Origenes

    I do not see how this has any impact on GPuccio’s argument. His argument is very clear and straightforward. As of yet I do not see any weaknesses and hence no wiggle room.

    The counter argument I see form the evolutionists including Dr Swamidass is the large functional space argument. I don’t personally think it is credible but they are using it.

    The issue would be that what we see historically from comparative homologous genes is only some of the potentially functional space. To test this you would have to change sequences in the animal and see if they work which is certainly not practical.

    If I am wrong here please correct me. I am simply trying to understand the arguments. How would we show that the large functional space is an invalid argument?

  44. 44
    es58 says:

    this is an interesting discussion anyone volunteer to provide cliff notes?

  45. 45
    Dionisio says:

    gpuccio @36:

    basically the protein information jumps would have to be the result of some of the changes included within the given Delta(x) (referenced @35), which includes other changes (eg. GRN, etc.) besides the protein information jumps.
    Delta(x) is the description of all the spatiotemporal changes needed to convert Dev(ca) to Dev(d1) or Dev(d2) in the problem described @35.

  46. 46
    gpuccio says:

    bill cole:

    The “large functional space argument” is just a myth, supported only by no logical or empirical evidence, just simple propaganda like the many times discussd Szostak paper.

    of course, it is the extrema ratio of darwinist to give some mythical credibility to their anti-empirical theory.

    A lot of empirical evidence, from tthe presenc of 2000+ protein superfamilies to Axe’s experiments to Hayashi’s rugged landscape paper, confirm that the prtoein functional space is extremely small and not connected at all.

    The simple problem is: should we follow ideological dogma or empirical evidence?

    However, this is certainly one issue that can and will be definitely solved as our understanding of protein function increases, as it will.

    But I suppose that then darwinists will invent some other myth…

  47. 47
    gpuccio says:

    Dionisio:

    “basically the protein information jumps would have to be the result of some of the changes included within the given Delta(x) (referenced @35), which includes other changes (eg. GRN, etc.) besides the protein information jumps.
    Delta(x) is the description of all the spatiotemporal changes needed to convert Dev(ca) to Dev(d1) or Dev(d2) in the problem described @35.”

    Well, you are certainly right about that!

    Of course the functional engineering of the proteome is only the tip of the iceberg. A lot of other, major functional changes are certainly needed, and they are probably even more important, and they almost certainly imply even more new functional information, probably a lot more.

    You well know that I am focusing on the proteome only for methodological reasons! 🙂

  48. 48
    gpuccio says:

    Origenes (to bill cole):

    “In that case you will be very impressed by those massive information jumps.”

    Well, I certainly am! 🙂

    When the final numbers started to come for the whole proteome, I was really impressed. Millions of functional bits!

    I am the first to be amazed. 🙂

  49. 49
    gpuccio says:

    es58:

    “this is an interesting discussion anyone volunteer to provide cliff notes?”

    I don’t know… But you are certainly welcome to ask about any aspect of the discussion, and I will be happy to answer. 🙂

  50. 50
    Dionisio says:

    gpuccio @47:

    Of course the functional engineering of the proteome is only the tip of the iceberg.

    I consider that “tip of the iceberg” a very important part of the spatiotemporal changes included within the whole developmental Delta(x).
    It’s like modifying object classes in order to boost their capabilities when doing object-oriented software development.
    That’s one of the reasons why I like the thorough research you’re doing on the discussed topic.

    I just wanted to confirm the association of the protein information jumps with the Delta(x) component of the above mentioned Dev(x) equations.
    We both seem to agree that the Delta(x) includes other important concepts, but I wanted to confirm that the protein information jumps are a required ingredient of the Delta(x).
    A high cuisine chef requires the right ingredients for his recipes.
    The designer requires the right components and tools in order to implement the design.

    We see different proteins involved in the morphogen gradient formation and interpretation processes. Also see different proteins involved in the innate and the adaptive immune system.
    It would be very interesting to review them all from your informational perspective in light of their functions in the given contexts. As more discoveries are made in the wet and dry labs, more questions get answered but new questions are raised. Perhaps some of those issues deal with novel proteins or previously unobserved protein functionality. Your thorough informational analysis should provide very helpful illustration of the given situations, thus facilitating the understanding of the whole picture.

    I look forward to seeing more of this kind of articles written by you here.

  51. 51
    Dionisio says:

    Minor misspelling (swapped letters): ‘or’ ‘ro’
    Cor… Cro…

    Sauropsida (Corcodylia) – Synapsida (Metatheria, Marsupialia): about 310 My ago

    Crocodylia?

  52. 52
    Dionisio says:

    gpuccio @48:

    I am the first to be amazed.

    Join the club! 🙂

  53. 53
    gpuccio says:

    Dionisio:

    “Crocodylia?”

    Corrected. 🙂

  54. 54
    gpuccio says:

    Dionisio:

    “It’s like modifying object classes in order to boost their capabilities when doing object-oriented software development.”

    That’s exactly what I think. For many proteins, some basic biochemical function can remain similar, and is usually implemented by more conserved domains.

    But “the interface” of the object often requires important adjustments in different context (species, groups of organisms, phyla). That interface can be implemented by changes in less conserved domains, or even in parts of the molecule that do not exhibit obvious domain structure, including intrinsically disordered parts.

    Transcription factors are a good example: the DNA binding domain is usually the most conserved part of the molecule. But TFs do not simply interact with DNA: they interact with one another, often in complex cumulative structures, and with other molecules and biochemical pathways.

    That part, the “regulatory” part, that in the end determines what the TF bound to DNA will do, is much less understood, and often less conserved, probably because it is functionally tweaked to different final functions.

    “We both seem to agree that the Delta(x) includes other important concepts, but I wanted to confirm that the protein information jumps are a required ingredient of the Delta(x).”

    Yes, of course they are. I believe that part of the regulatory procedures (but only part of them) is implemented through functional modifications of the proteome itself, especially in its less understood parts.

    “A high cuisine chef requires the right ingredients for his recipes.
    The designer requires the right components and tools in order to implement the design.”

    Absolutely!

    One of the main observations that I would do starting from the data I have presented here is: there is much more specific function in the proteome than is usually believed.

    “We see different proteins involved in the morphogen gradient formation and interpretation processes. Also see different proteins involved in the innate and the adaptive immune system.”

    Those are very good examples of what we have said before. 🙂

    “It would be very interesting to review them all from your informational perspective in light of their functions in the given contexts. As more discoveries are made in the wet and dry labs, more questions get answered but new questions are raised. Perhaps some of those issues deal with novel proteins or previously unobserved protein functionality.”

    It is, definitely, very interesting. I am already doing that. And I am very confident that our general understanding of protein function will rapidly increase. And many darwinist myths will be demolished and destroyed in that process.

    “I look forward to seeing more of this kind of articles written by you here.”

    They will come…

  55. 55
    Dionisio says:

    gpuccio @54:

    there is much more specific function in the proteome than is usually believed.

    Excellent! Can’t wait to see more.

    […] our general understanding of protein function will rapidly increase. And many darwinist myths will be demolished and destroyed in that process.

    Great! They ain’t seen nothing’ yet. 🙂

    Thanks.

    BTW, where are the politely-dissenting interlocutors now?
    What about the loud voices that claim this site lacks scientific flavor?
    It can’t get more scientific than this thread.
    Did they run out of serious arguments?
    🙂

  56. 56
    Eric Anderson says:

    I agree with Armand Jacks.

    Definitely a lot of work here and well worth publishing.

    I know it is a pain in the neck and can take months of tedious back-and-forth and waiting (at least with a traditional journal), but it might be something worth seriously considering.

  57. 57
    gpuccio says:

    Eric Anderson:

    There are many reasons why I don’t want to engage in trying to publish this kind of personal results in a traditional scientific journal.

    Moreover, I am not sure that any journal would publish the results after they have been published online on this blog. 🙂

    I wondered about that problem too, and my decision was to go this way. The results are here. They are public. I am available to any discussion, proposals, future analysis, and whatever. For the moment, that’s what I want to achieve.

    Thank you for your kind suggestion, however. It is always satisfying to get interest and feedback for our work! 🙂

  58. 58
    gpuccio says:

    Eric Anderson:

    One important consideration (but not the only one) is that I want to be able to show this results as an explicit support to the theory of ID, and in no other way. That’s why I have done the work, that is its purpose and motivation. My only aim is to support in some way the scientific case for ID.

    Do you really think that any traditional scientific journal would accept such an approach?

  59. 59
    Phinehas says:

    GP:

    I hear you. The moment you move toward publishing in a journal, I think politics would become the primary concern rather than science. That’s a sad commentary on the state of scientific journals, but there you go.

  60. 60
    bill cole says:

    Gpuccio
    Yes the Szostak paper is often cited. This is to bind to ATP and the number is 1/10^11 for proteins of 80 AA. My argument has been.

    -binding one small molecule is trivial compared to living proteins that have to bind to multiple proteins, such as nuclear proteins.

    -even if Szostak numbers are accurate how do you build a spliceosome, which is the bacteria to yeast transition with 200 proteins even if Szostak’s numbers are right?

    Thoughts?

  61. 61
    gpuccio says:

    bill cole:

    I have commented many times on the Szostak paper, and each time I seem to awaken the rage of some darwinist.

    Your objections are perfectly right, but IMO the main, huge bias in that paper is the following:

    They use artificial selection after induced random variation to get the result. Therefore the protein that they analyze was not in the original random repertory, but is the result of protein engineering, IOWs of design

    The sequences in the original random repertory exhibited just a weak affinity for ATP. While the authors are ready to label that as a biological function, the simple truth is that such a “function” is completely irrelevant in a cell context. In particular, it could never confer a reproductive advantage, and be selected by NS.

    Of course, it can instead be selected by artificial selection, because artificial selection can select any level, however low, of detectable function. And that’s exactly what they did. They selected a weak and irrelevant affinity for ATP and generated, by a process of trivial protein engineering, an artificial protein (that is not the sequence present in the original repertory) with a much stronger affinity for ATP and some basic folding.

    Therefore, the number of 1/10^11 for proteins of 80 AA means absolutely nothing for the darwinian scenario. No naturally selectable function is present in that kind of repertory. Of course, we can find in it any kind of weak biochemical affinities, and enhance them by artificial selection.

    IOWs, the only meaning of Szostak’s paper is that bottom up protein engineering, if performed by a good biochemist, can work.

    But there is more. Even the engineered protein, the one with strong affinity for ATP, is definitely not naturally selectable. If added to a cellular context, it only reduces fitness, as shown by a later experiment. The reason is very simple: just binding ATP is of no use in a cell context, it can only subtract precious ATP to the enviromnment.

    Sometimes darwinists seem to forget that not any function is good in a cell environment. Many “functions” are simply useless, or detrimental.

    Well, now let’s wait for the rage, again! 🙂

  62. 62
    Eric Anderson says:

    gpuccio @61:

    Excellent points and critique.

    —–

    Sometimes darwinists seem to forget that not any function is good in a cell environment. Many “functions” are simply useless, or detrimental.

    This is such a crucial and fundamental point for any complex, functional system. It would be nearly impossible to overemphasize this point. We cannot simply throw functions into a complex, functional system and get advantageous outcomes.

    The Darwinian paradigm has had such a hard time coming up with decent examples of additional fuction. The problem, as has often been pointed out, is due to the lack of resources and the massive search space. It is a daunting task.

    But even if by chance a purely natural process stumbles upon a new “function”, it still has to be integrated into the cellular machinery, instructions have to be appropriately included in the repertoire and faithfully passed on to the next generation, and on and on.

    This is an engineering problem.

    And if we step back for a moment from the weeds, like Szostak’s paper, to look at the big picture, we can see that this is a massive conceptual problem for the evolutionary paradigm at large.

    One simply cannot go around randomly introducing new “functions” into a complex, functional system like a cell and expect anything good to come of it.

    The evolutionary construct is unworkable, not just at the detailed level of a protein here or a protein there there. It is fundamentally unworkable across the whole spectrum of changes that allegedly would have had to occur across biology and across time.

    The entire edifice is built upon an incredibly naive and simplistic view of how complex, functional systems operate.

  63. 63
    Dionisio says:

    gpuccio’s thorough research work is better than many papers I’ve seen lately -and I’ve seen quite a bit of them these days (just look at the thread “a third way of evolution”).
    Nevertheless, I think I understand his decision to provide serious scientific arguments in an ongoing public debate that sometimes lacks scientific rigor.

  64. 64
    gpuccio says:

    Eric Anderson:

    “But even if by chance a purely natural process stumbles upon a new “function”, it still has to be integrated into the cellular machinery, instructions have to be appropriately included in the repertoire and faithfully passed on to the next generation, and on and on.

    This is an engineering problem.”

    These are fundamental points. thank you for raising them

    One very interesting thing that, IMO, emerges from the data presented here, is that they seem to be a coordinate change. That’s why we have such huge “jumps” in information content.

    This is a very important point.

    If we look at Figures 4 and 5 (the last two figures in the OP, we can see many interesting things, but one thing is particularly interesting, and maybe not so obvious:

    The almost identical form of the density curve for cnidaria and cephalopoda.

    The two curves are really so similar that a casual observer really should wonder why.

    Now, let’s consider that:

    a) Cnidaria are a phylum of Radiata, while Cephalopoda are a quite evolved class of the phylum Mollusca, in the superphylum Lophotrochozoa, which is part of Protostomia in the clade Bilateria. While we cannot be sure of how chronologically distant these two groups of organisms are
    (the problems inherent in the Cambrian explosion make any final assessment very difficult), there is no doubt that Cnidaria and Cephalopoda are extremely distant from practically all major points of vew, starting from body plan simmetry.

    b) And yet, id we evaluate those two groups for their content of human related sequences, they behave almost in an identical way. That si really surprising and interesting.

    c) Now, I want to be very clear about one aspect: when we analyze the content in human conserved information, we are in no way looking at the total functional information in an organism, but only to the subset of functional information that is conserved also in the human lineage after the relevant split.

    d) To be more clear, I am in no way saying that Cnidaria and Protostomia have the same amount of functional information, or that they do not differ for specific functional information. This is an important point. For example, Cephalopoda may well have a lot of speicif functional information that makes them different from Cnidaria. They probably have millions of bits of functional information that are Cephalopod-specific. But here we are not looking at that.

    We are simply looking at the functional information that is conserved up to humans. And that functional information is extremely similar in Cnidaria and Cephalopoda. It is not only very similar as total content in bits (a little more than 5 million bits, not corrected for redundancy). It has also almost the same density distribution when evaluated as baa values for each single protein.

    e) So, in the measure that these two very different groups have human conserved information, we can say that such human conserved information is almost the same in the two groups.

    f) Now, even if 5 million bits are certainly a relevant bulk of information, they are only a minor part of the total information that we can observe in humans. They very likely correspond mainly to old protein systems, very conserved even before the animal stage. Fundamental, house keeping functional systems, that are transmitted and conserved for hundreds of millions of years, often for billions of years. Much of that information can certainly be traced, still with good conservation, up to LUCA and OOL.

    g) But then, first at the level of deuterostomia, and then, much more, at the level of the first vertebrates, we have what could be called as a sudden “explosion” of human conserved functional information: 1.7 million bits in the first deuterostomia, 3.7 million bits in the first vertebrates (not corrected for redundancy). A very big explosion, equivalent to the sum total of the human conserved functional information that had been accumulated from OOL to the whole group of protostomia. And it happens in two well separated steps.

    h) What does that mean? IMO, there is only one reasonable interpretation: with the appearance of deuterostomia first, and then with the appearance of craniata-vertebrata (cartilaginous fish), new bodily plans are introduced. And they are introduced rather suddenly from an evolutionary standpoint. And they are introduced in a coordinated way.

    i) So, I think these data really support the points that you have so brilliantly made: not only the appearance of the first vertebrates required 3.7 million bits of new specific information (1.7 million bits of which unique), but there are all the reasons in the world to believe that such bulk of new information is highly coordinated. The whole bulk of new information contributes to make vertebrata different from previous deuterostomia, and to implement a really new biological plan that will then be carried on more or less gradually in the hundreds of million years that will follow. For example, one of the most striking features of the new lineage will be cephalisation, the concentration of brain functions in the head. Another one will be the development of adaptive immunity.

    This is design in its highest form.

    I hope I will be able to give further insights about these points when I will present other data about the evolutionary pattern of different kinds of proteins.

    And, just to finish, let’s remember that this is only the proteome, and that behind it there is much, much more.

  65. 65
    Dionisio says:

    Interesting discussion indeed.

  66. 66
    DATCG says:

    Nice post Gpuccio. Congrats and thanks for all your hard work. Always enjoy your post. Enjoyed reading this, past post and discussion.

    On yours and Dioniso discussion #50/#54.

    Dionisio:
    “It’s like modifying object classes in order to boost their capabilities when doing object-oriented software development.”

    Gpuccio:
    “That’s exactly what I think. For many proteins, some basic biochemical function can remain similar, and is usually
    implemented by more conserved domains.”

    Was thinking there must be core, conserved domains, but with Prescribed tolerance levels of variation across systems.

    When Dionisio brought up Object Class modifications, it struck a chord.

    I’ve always looked at biological functions through Programmers perspective as functions in a Common Design Depository of component systems

    Blueprints, regulators, switches, and data references.
    All utilized by different Rules-based Regulatory Routines and/or Sub-Routines.

    Seeing how Enhancers work, coordination, collaboration takes place with Master Regulators, we live in fascinating times.

    Looking forward to your next post.

  67. 67
    DATCG says:

    Then there’s the Brain. Yet more discoveries of previously ignored areas. How many areas exist like this? Of “types of molecules not previously thought to produce proteins?”

    Just how large an area exist still yet undiscovered today? ENCODE I think said at least 80% of what was previously written off as JUNK might be functional?

    Question – is there any areas so far in actual research that is absolute JUNK? No function, no purpose, not utilized by other systems – just trash? It seems every single day, old Junk is being discovered as No Junk.

    Research shows that circular RNAs, until now considered non-coding, can encode for proteins

    This discovery reveals an unexplored layer of gene activity in a type of molecule not previously thought to produce proteins. It also reveals the existence of a new universe of proteins not yet characterized.

    To determine whether circRNAs are translated, the researchers used Drosophila (fruit flies) and developed or adapted various techniques from molecular biology, computational biochemistry and neurobiology.

    They also found that translated circRNAs are associated with specific places in the cells, in particular synapses, the junctions where electrical impulses pass from one nerve cell to another nerve or muscle cell. Indeed, the proteins produced from these circRNAs are present in synapses and are translated in response to specific signals, e.g. when the flies did not have access to food for 12 hours.

    This suggests that communication between neurons might involve unknown and uncharacterized mechanisms. Moreover, starvation and other pathways that induce the translation of circRNAs are also involved in aging, suggesting a strong link between circRNA translation and aging and a possible role for these molecules in neurodegenerative diseases.

    As circRNAs are extremely stable, they potentially could be stored for a long time in compartments more distant to the cell’s body like axons of neuron cells. There, the RNA molecules could serve as a reservoir for proteins being produced at a given time.

    Reservoir or Depository, take your pick. I came across this after I discussed a “Depository”

  68. 68
    gpuccio says:

    DATCG:

    Thank you for the kind words! 🙂

    You raise important and fascinating points:

    “When Dionisio brought up Object Class modifications, it struck a chord.”

    Absolutely! The working of biological objects is definitely similar to very good Object Oriented Programming.

    Protein domains are probably the main core objects, with a lot of ability for conservation of core function and tweaking of interface. The same reasoning can be done for the whole protein as a meta-object. And so on.

    And I would like to mention here two very big systems hat work as huge networks based on well programmed and flexible objects: the network of Transcription Factors and the amazing system based on Ubiquitin, E1 and E2 ubiquitin enzymes and especially E3 ubiquitin protein ligases, and the proteasome.

    “I’ve always looked at biological functions through Programmers perspective as functions in a Common Design Depository of component systems”

    Absolutely! Think also of the fundamental regulator activity of small molecules, like miRNAs and small peptides. Fascinating stuff indeed. And a global meta-setting that is incredibly complex and incredibly flexible (the global epigenetic levels of programming), and can rapidly change in an extremely coordinated way from cell type to cell type, ad even in the same cell type in different contexts!

    “Just how large an area exist still yet undiscovered today? ENCODE I think said at least 80% of what was previously written off as JUNK might be functional?”

    Yes, and they have been strongly criticized for that! But time will tell. 🙂

    Indeed, there is a strong crusade against function, the most imbecile intellectual war ever fought, whose only purpose is to constrain observed, exuberant, amazing biological function in the narrow limits of present dogma and little imagination (how strange, in an academic class that has such huge imagination in elaborating darwinian fairy tales! 🙂 ).

    “Question – is there any areas so far in actual research that is absolute JUNK? No function, no purpose, not utilized by other systems – just trash?”

    Maybe classical neo-darwinism? OK, just joking… 🙂

  69. 69
    Eric Anderson says:

    DATCG @67:

    Question – is there any areas so far in actual research that is absolute JUNK? No function, no purpose, not utilized by other systems – just trash? It seems every single day, old Junk is being discovered as No Junk.

    The problem is that we know almost nothing about what is actually happening in the cell — from an engineering standpoint. We are still engaged in very crude reverse-engineering attempts: knock out a gene here, mutate a sequence there, and see what happens. Until we actually know what is doing what — precisely what the entire coding system is and what it means and how it plays out in the larger context — it will be impossible to draw a definitive conclusion that something is junk.

    But we can see some important developments and draw some initial conclusions. Let’s consider so-called “junk DNA” for a moment:

    Even if we can’t seem to find a function for a particular sequence, it doesn’t mean it doesn’t have one.

    1. There is the obvious possibility of redundancy.

    2. There may be pathways that are important for some stages of development and not others, thus making it more difficult to identify whether it lacks function, particularly with experiments that don’t track the entire lifecycle of the organism.

    3. There may be functions that are there for a particular purpose or particular environmental condition and which won’t be manifest immediately.

    4. There may be functions that contribute to overall fitness of the organism/population over generations, but which would not be evident over a few generations in short-term knockout studies.

    5. There may be functions that are not critical to the organism, but which still contribute to overall health, performance, quality of life, etc. These nuances can easily be missed in knockout experiments.

    6. There may be front-loading — sequences that are not necessary for the organism currently, but which were in the past or could become so later on.

    7. Finally, there are thousands upon thousands of biological functions and processes that we know exist and for which clear genetic instructions have not yet been identified — vastly more in fact, than what has thus far been identified. It follows as a matter of logic that either (a) a significant amount of allegedly-non-functional DNA will turn out to have function, or (b) the known functional DNA will turn out to have many more layers of multiple-functionality than currently thought. Or a combination of the two.

    —–

    Finally, let us remember one additional overarching fact:

    Every time we find an additional function, we are adding to the amount of known functional DNA. In contrast, we will essentially never discover that a known functional sequence is no longer functional.

    Thus, as more research is being done, we can only add to the known functional DNA. In other words, whatever percentage of functional DNA is currently known, the percentage can only increase, not decrease. The arrow of discovery and the trend of research is very clear on this point, both logically and practically, as witnessed by it seems almost daily new discoveries in functionality.

    Anyone who still clings to the outdated and simplistic Darwinian talking-point of pervasive amounts of junk DNA is not only incredibly naive about how complex, functional systems work in the real world, but is also standing firmly on the wrong side of the trajectory of the evidence.

  70. 70
    gpuccio says:

    Eric Anderson at #69:

    Very good thoughts! 🙂

  71. 71
    Dionisio says:

    gpuccio @68:

    The working of biological objects is definitely similar to very good Object Oriented Programming.

    [emphasis added]

    Excellent point, though in this particular context very good is an understatement. 🙂

    I worked for over two decades on software development for engineering design.

    The level of cybernetic solutions we’re seeing in the biological systems was simply unimaginable to me or my fellow colleagues, even in our wildest daydreaming after many sleepless nights. 🙂

    Just imagine -if you will, that we could design a building in such a way that we just place our design product (shaped as a small sphere) within an enclosed frame, push a button to start the build process and voilà! The only caveat is that the frame has connectors to supply generic materials to the construction when required. That’s it. Bingo!
    Even that is not comparable. The building isn’t conscious. But we can leave that aside for now. 🙂
    Unbelievable!

    When one of my children left at home a textbook on human development after graduating from medical school, I dared to open it and all my learned concepts on complex systems and information technology were totally blown up into pieces. I haven’t recovered since. Actually, it got worse from that point on. What started as curiosity soon turned into a growing fascination which eventually became an irresistible addiction to searching for newer information to understand how all that stuff works.
    Well, needless to say I had to leave the previous job and start a new career in a completely unknown field from scratch. It’s been a long and winding road that has led to many doors of new information that answered some outstanding questions while raising new ones. Unexplainably, the fascination keeps growing as I dig deeper into the marvelous functioning of the biological systems, from my very limited perspective and much more limited intellectual knowledge and capacity to understand the difficult issues that appear before me in the literature I review. Definitely it’s been very humbling.

    BTW, Professor Uri Alon described a kind of comparable situation he experienced after getting his PhD in Physics and looking at a biology book. He told that interesting story in the first class of his 2014 course on Systems Biology at the Weizmann Institute for Science. The 15-lesson video course is available online to anyone interested in that subject.
    For the same reasons interdisciplinary work teams are becoming standard in biology-related research these days.
    We ain’t seen nothin’ yet.
    The best is still ahead.

  72. 72

    Eric,

    Until we actually know what is doing what — precisely what the entire coding system is and what it means and how it plays out in the larger context — it will be impossible to draw a definitive conclusion that something is junk.

    I think this is one of major benefits of the Venter program — to minimize the operating system until we can better isolate the collective function of the minimal genome.

    Materialists so often come here to scorn, and ask where is the research that supports ID. It all does.

  73. 73

    It is a physical certainty that if one of Szostak’s (or Joyce’s or Lincoln’s, etc) intellectual descendants ever creates a homogeneous self-replicator, they will most certainly have to add a semiotic component to the system in order to get it to function.

    One wonders if even that will finally be enough to infer design in biology among materialists?

  74. 74
    Dionisio says:

    gpuccio @68:

    And I would like to mention here two very big systems hat work as huge networks based on well programmed and flexible objects: the network of Transcription Factors and the amazing system based on Ubiquitin, E1 and E2 ubiquitin enzymes and especially E3 ubiquitin protein ligases, and the proteasome.

    Wow! Very interesting. Thanks.

  75. 75
    Dionisio says:

    gpuccio @68:

    Think also of the fundamental regulator activity of small molecules, like miRNAs and small peptides. Fascinating stuff indeed. And a global meta-setting that is incredibly complex and incredibly flexible (the global epigenetic levels of programming), and can rapidly change in an extremely coordinated way from cell type to cell type, ad even in the same cell type in different contexts!

    Wow! Very interesting. Thanks.

  76. 76
    Dionisio says:

    gpuccio @68:

    Indeed, there is a strong crusade against function, the most imbecile intellectual war ever fought, whose only purpose is to constrain observed, exuberant, amazing biological function in the narrow limits of present dogma and little imagination (how strange, in an academic class that has such huge imagination in elaborating darwinian fairy tales!

    That’s an interesting comment on the sad reality of academic circles today.
    Perhaps the appearance of the third way and the latest book from professor D. Noble shows that not all scientists remain dogmatic, and some have started to be more open-minded and think out of outdated boxes.
    However, even the new dissenting voices still seem confused about how to approach the strong evidences presented by the latest research.

  77. 77
    Dionisio says:

    Eric Anderson @69:

    The problem is that we know almost nothing about what is actually happening in the cell — from an engineering standpoint. We are still engaged in very crude reverse-engineering attempts: knock out a gene here, mutate a sequence there, and see what happens. Until we actually know what is doing what — precisely what the entire coding system is and what it means and how it plays out in the larger context — it will be impossible to draw a definitive conclusion that something is junk.

    Excellent description of the situation. Thanks.

  78. 78
    Dionisio says:

    Eric Anderson @69:

    Regarding the so called “junk” DNA, I wouldn’t be surprised if we have some cellular or molecular mess resulting from the messy human history. IOW, things that used to work but got messed up and stopped working right or completely.
    Well designed things that get abused and/or misused losing their functionality partially or completely.
    The amazing fact that despite such a messy history the robust biological systems have survived speaks volumes about the kind of design we’re looking at.

  79. 79
    gpuccio says:

    Dionisio, Eric Anderson, UB, DATG, bill cole, phineas:

    Excellent discussion, my friends. Thanks to all of you for your precious contributions.

    Let’s try to go deeper and deeper, this is the right way to discuss ID theory, IMHO. 🙂 🙂

  80. 80
    Dionisio says:

    gpuccio,

    I like your honesty adjusting the results for redundancy.

    That’s a lesson on honest approach to interpretation of scientific research results.

    Thanks.

  81. 81
    Dionisio says:

    gpuccio,
    Given my poor reading comprehension, you may feel free to laugh at my naïve comments and dumb questions related to the following part of your article:

    In each split, humans derive from the second line:
    Cnidaria – Bilateria. Let’s say at least 555 My ago.
    Protostomia – duterostomia. Let’s say about 530 My ago.
    Pre-vertebrate deuterostomia (including chordates like cephalocordata and Tunicates) – Vertebrates (Cartilaginous fish). Let’s say 440 My ago.
    Cartilaginous fish – Bony fish. Let’s say about 410 My ago.
    Bony fish – Tetrapods (Amphibians). Let’s say 370 My ago, more or less.
    Amphibians – Amniota (Sauropsida, Crocodylia): about 340 My ago
    Sauropsida (Crocodylia) – Synapsida (Metatheria, Marsupialia): about 310 My ago
    Metatheria – Eutheria (Afrotheria): about 150 My ago
    Atlantogenata (Afrotheria) – Boreoeutheria: probably about 100 My ago.

    The simple rule is: for each split, the second member of each split is the line to humans, and the human conserved information present in the first member of each couple must have been conserved in both lines at least from the time of the split to present day.

    So, for example, the human-conserved information in Cnidaria has been conserved for at least 555 MY, the human-conserved information in Crocodylia has been conserved for at least 310 My, and so on.

    In this sentence:
    “In each split, humans derive from the second line:”
    does the word ‘line’ refers to ‘branch’ coming out of the split?
    Is the first line “Cnidaria – Bilateria” the first split?
    What did that split from?
    According to your explanations, is the Bilateria branch the one leading to humans?
    If I got that right, then is the next line (Protostomia – duterostomia) the split from the Bilateria branch?
    The following line then splits from “duterostomia” and so on?
    Thanks.

  82. 82
    gpuccio says:

    Dionisio:

    Yes, I would say that you get it right.

    Each split is between two different evolutionary branches: the first one becomes separated from the second, and the second one is the lineage from which humans are derived.

    For clarity, the human lineage, according to current evolutionary models, could be grossly described as follows (please note that I am not en expert, and that the following concepts are neither complete nor necessarily precise: it’s just my best understanding):

    Domain: Eukaryota
    Kingdom: Animalia (Metazoa)
    Subkingdom: Eumetazoa
    (unranked): Bilateria
    Superphylum: Deuterostomia
    Phylum: Chordata
    Subphylum: Vertebrata
    Infraphylum: Gnathostomata
    Subgroup: Osteichthyes (Bony fish)
    Supercalss: Tetrapoda
    Clade: Amniota
    Clade: Synapsida
    Class: Mammalia
    Subclass: Theria
    Clade: Eutheria
    Magnorder: Boreoeutheria
    Order: Primates

    So, just to review briefly the splits I have considered:

    Cnidaria – Bilateria

    This is based mainly on boy symmetry. Cnidaria are Radiata. For Bilateria I have considered Cephalopoda, a class of Mollusca, because they are Bilateria but Protostomia, and among Protostomia they are extremely near to Deiterostomia (at protein homology level). As I ahve explained, using all Protostomia sequence would have been too time consuming, so I chose Cephalopoda as a representative sample.

    Of course, humans derive from Bilateria, and not from Radiata. Therefore, the human homology present in Cnidaria can be traced to before the split to Bilateria, IOWs to the common ancestor of Radiata and Bilateria. Before the split.

    Let’s go to the second split:

    Protostomia – Deuterostomia

    Here I use again Cephalopoda as representative of Protostomia, and the whole group of Deuterostomia (excluding vertebrates). In the Bilateria group, humans derive from Deuterostomia, not from Protostomia. therefore, the huamn conserved homology in Cephalopoda can be traced to the common ancestor of Protostomia and Deuterostomia. Before the split.

    Third split:

    Pre-vertebrate Deuterostomia – Vertebrates (Cartilaginous fish)

    This is the important split for the discussion about the vertebrate proteome. So, let’s look at it better.

    First deuterostomia include Echinodermata, Hemichordata and the first Chordata (Cephalochordata and Urochordata), if we exclude vertebrates.

    Vertebrates appear first as Agnatha (jawless fish, today’s lampreys), then as Gnatostomatha, that split very quickly into Cartilaginous fish and Bony fish.

    So, the human conserved information in Deuterostomia not vertebrates can be traced to the common ancestor of vertebrates and other deuterostomes. That represents the highest level of human conserved information in animals that are not vertebrates. Of course, humans derive from the Vertebrate branch.

    Instead, the human conserved information in Cartilaginous fish can be traced to the common ancestor of Cartilaginous fish and Bony Fish. Humans (and, in general Tetrapoda) derive from Bony fish, so the human conserved information in Cartilagionus fish can be traced to some time after the Non vertebrates – Vertebrates split and before the Cartilaginous fish – Bony fish split.

    You may observe that I have not considered jawless fish (lampreys) in my analysis. That is mainly due to methodological problems: lampreys are an extremely small group of organisms, and they are scarcely represented in the NCBI database of proteins (just a few hundred sequences). Therefore, it is practically impossible to perform a reliable analysis on those data.

    Well, I hope that this helps clarify the methodology I have used.

  83. 83
    DATCG says:

    #69 – Eric A.,

    “The problem is that we know almost nothing about what is actually happening in the cell — from an engineering standpoint. We are still engaged in very crude reverse-engineering attempts:”

    Thanks, reviewing and highlighting those areas, especially Redundancy to lead off. Then knockout experiments, never forget jumps to conclusions by Darwinist citing as evidence, turned out to be wrong. I agree, still at “crude” stage of reverse-engineering. And just to meet these levels of reverse-engineering requires best in technological innovations by researchers to view, let alone untangle and comprehend precise order, collaboration and coordination of the organized systems.

    I briefly debated a Darwinist once on Redundancy several years ago who thought Redundancy was a prime example of Darwinist prediction for JUNK DNA showing unguided process.

    Purely from a Design point of view, responded stating Redundancy can actually be a sign of highly efficient planning features that intelligent agents – ourselves – use daily in programming and networked systems for matters of efficiency, speed, for access around the globe. Including overcoming any disruptions to the systems to prevent downtime to live applications. Therefore, if biological functions are designed for survival I would expect to find built-in Redundancy for many logical reasons, not the least of which is prolonging survival during extremes or circumstances that might suppress certain areas, so that the need arises for differentiation and duplicate genes.

    I agree we’re just scratching the surface of what ENCODE unearthed and it’s wide open for discovery.

    The link I posted on circRNA above is an example of how new discoveries are taking place for previous areas once assumed not to encode for proteins. Excerpt from the article…

    This discovery reveals an unexplored layer of gene activity in a type of molecule not previously thought to produce proteins. It also reveals the existence of a new universe of proteins not yet characterized.

    “… new universe of proteins not yet characterized.”

    That’s quite a description about their discovery.

  84. 84
    DATCG says:

    Gpuccio, again thank you. Yes, enjoying this discussion and look forward when I have more time to fully review this and previous post of yours.

  85. 85
    DATCG says:

    Eric A.,

    On Redundancy, one paper cites advantages…

    “Organisms may exploit mutual repression among such redundant regulators, for example, to overcome stochastic fluctuations in protein expression. In such cases, expression of one redundant copy may be induced when expression of the repressing partner is temporarily reduced, thus negating the disruption.”

    From 2009, they mention evolution, but this can be a result of Prescribed planning or Front Loading as you mention…

    Genetic Redundancy: New Tricks for Old Genes

  86. 86
    Eric Anderson says:

    Dionosio @80:

    +1

    Yes, I noticed the same thing when reading and appreciated the careful, honest approach gpuccio took.

  87. 87
    Eric Anderson says:

    Dionosio @78:

    Yes, that is why I try to use a qualifier, like “pervasive amounts.” Both Darwinian theory and design can accommodate some amount of junk. The difference is in the expectations.

    Well, that and the real-world realities of engineering.

    Anyone who thinks the genome is littered with junk, that some 90%+ of DNA is junk, or any similar percentage is incredibly naive and doesn’t have any idea what they are talking about from an engineering standpoint.

    The remarkable thing, is that even after all these years we still hear the occasional Darwinist claim that DNA is almost all junk — clinging desperately to yet another failed Darwinian claim . . .

  88. 88
    gpuccio says:

    DATCG:

    I am completely with you about redundancy as a fundamental feature of complex engineered systems.

    A diploid genome is a basic example of redundancy.

    The multiple, interconnected signaling pathways from cell membrane to nucleus are reasonably another example.

    The combinatorial action of Transcription Factors could well qualify, too.

    But the most astounding levels of complex, stratified, interconnected, regulated redundancy are probably to be observed in epigenetics.

    Have you ever wondered at how DNA metilation, chromosome 3D architecture, histone post-translactional modifications, RNA splicing, microRNAs, mRNA methylation, and who knows what else, all seem to contribute to parallel cross regulations of final transcription, so much so that it is really difficult even to begin to disentangle that multiple, redundant, wonderfully complex network of meanings?

  89. 89
    gpuccio says:

    Dionisio:

    “I like your honesty adjusting the results for redundancy.”

    Eric Anderson:

    “Yes, I noticed the same thing when reading and appreciated the careful, honest approach gpuccio took.”

    I am really glad that you appreciated that. It was not an easy task.

    In the beginning, when I became conscious of the problem, I had no idea of how to solve it. I was tempted to just acknowledge it, and hope that its relevance was not too great.

    Then I made some cautious attempt at trying to quantify it, and at some point I realized that it was really possible to correct it in a satisfying quantitative way.

    I am rather satisfied with the result, even if for simplicity I have not given the details of how it works.

    I do think that having found that about half of the human proteome can be traced to repetition is in itself a fine result.

  90. 90
    Dionisio says:

    gpuccio,

    Yes, your detailed explanation did help to clarify the methodology you’ve used for your article. Thanks.

    It’s funny you wrote “please note that I am not an expert…”. In this topic you definitely seem like an expert to me.

    You’ve written on this same subject before and I thought I had understood it, but now I realized I had not grasped it quite well yet. It takes me longer than normal.

    BTW, I have not read much about this besides your articles in this site. I have difficulties memorizing so many names and don’t understand the classification criteria. BTW, are they based on physiological, phenotypic or genetic parameters?

    I’ve noticed an ongoing discussion in this site between common and uncommon descent, but I stay out of that debate, because don’t understand it well, and nobody has enough spare time to explain it to me well enough to ensure that I understand it.

    Perhaps some folks are laughing while seeing someone needed additional clarification of your clear article.

    This may help them understand my situation:
    Uri Alon’s 2014 System Biology course video is about 15-hour long, but it took me several months to watch it. Most people would have taken that course much faster.
    I couldn’t finish MIT Jeff Gore’s course, which is almost 10 hours longer. It was taking me too long and I had to move on with my project. That’s life. 🙂

    In any case, I’m glad you started this discussion thread.

    I would like to have an example of the evo-devo problem posted @35, using real data -maybe from the classification you provided? Do you think that’s feasible now?
    This could be a comprehensive illustration of a transition at one of the splits you’ve documented here.
    For example,
    ca = bilateria
    d1 = protostomia
    d2 = duterostomia
    Then knowing Dev(ca), Dev(d1) and Dev(d2), we could determine Delta(d1) and Delta(d2) as the required spatiotemporal physicochemical changes to resolve the equations. Actually, we could resolve just one of the equations, whichever is easier, based on the available information.
    We could choose a more recent split if we prefer to.
    Perhaps this is off topic here because it covers other things besides the proteome.
    Any objections, suggestions, ideas, corrections, comments?
    Thanks.

  91. 91
    gpuccio says:

    Dionisio:

    “BTW, I have not read much about this besides your articles in this site. I have difficulties memorizing so many names and don’t understand the classification criteria. BTW, are they based on physiological, phenotypic or genetic parameters?”

    I think they are based on the sum total of what is available. It is not a simple field, and experts are constantly debating about those things. Which is good.

    I suppose that the fossil record remains the foundation, but molecular data are a great contribution.

    Regarding you question about the equations, I think you are right, but how do you think we can set the equations, with so many components we still don’t understand?

  92. 92
    Dionisio says:

    gpuccio,

    Regarding you question about the equations, I think you are right, but how do you think we can set the equations, with so many components we still don’t understand?

    That’s an excellent question.
    I think you’re right about our current level of understanding on the subject. At this point, as far as I can see, your work on the proteome information jumps is perhaps the better known part of the Delta(x) components of the equations, but still does not tell us how those information jumps appeared. The Delta(x) components are not only about the observed differences in the mechanisms or the parts, but about the procedure leading to those differences in the mechanisms and parts. In the case of the proteome information jumps it would require to define the procedure(s) required to get those proteome differences inserted.

    As you mentioned earlier in this discussion, there are other things that must be accounted for, but are not well characterized or are poorly understood.

    But perhaps that’s the ultimate validation (falsification) test for the evo-devo conundrum. In order to determine Delta(d1) and Delta(d2) we must know very precisely Dev(ca), Dev(d1) and Dev(d2). Is there any workaround?
    Then, once those three main components are known, then we could work on determining the possible spatiotemporal physicochemical changes that could be included in Delta(d1) and Delta(d2).
    Does this make sense?
    Is there a better way to do this?
    Thanks.

  93. 93
    Dionisio says:

    gpuccio @88:

    Have you ever wondered at how DNA metilation, chromosome 3D architecture, histone post-translactional modifications, RNA splicing, microRNAs, mRNA methylation, and who knows what else, all seem to contribute to parallel cross regulations of final transcription, so much so that it is really difficult even to begin to disentangle that multiple, redundant, wonderfully complex network of meanings?

    I have started to wonder at that, but my thoughts have drifted away into fantasyland and I’ve felt kind of hypnotized and levitated or beamed up to the seventh heaven.
    Definitely that task is above my pay grade.
    My limited mind and poor understanding of biology, physics and chemistry don’t allow me to approach such a difficult task. I let the scientists figure out that.
    🙂

  94. 94
    gpuccio says:

    Dionisio:

    “Does this make sense?”

    Yes.

    “My limited mind and poor understanding of biology, physics and chemistry don’t allow me to approach such a difficult task.”

    You are in good company. Count me in! 🙂

  95. 95
    bill cole says:

    Gpuccio

    Indeed, there is a strong crusade against function, the most imbecile intellectual war ever fought, whose only purpose is to constrain observed, exuberant, amazing biological function in the narrow limits of present dogma and little imagination (how strange, in an academic class that has such huge imagination in elaborating darwinian fairy tales! ???? ).

    Yes, its a junk of the gaps discussion.:-)

  96. 96
    gpuccio says:

    bill cole:

    Junk of the gaps it is, definitely! 🙂

  97. 97
    Dionisio says:

    gpuccio,

    Maybe the evo-devo folks should give us some credits for trying to help them resolve their equations?

    🙂

  98. 98
    Dionisio says:

    bill cole
    What about Neo-Darwinism of the gaps?

    🙂

  99. 99
    Dionisio says:

    DATCG @67:

    https://phys.org/news/2017-03-circular-rnas-non-coding-encode-proteins.html

    Yes, that’s an interesting paper. Thanks.

  100. 100
    Dionisio says:

    Upright BiPed @5:

    I expect you may get caught up in cross-platform comments with TSZ, as you did in your last paper.

    Did that happen yet?

  101. 101
    gpuccio says:

    Dionisio:

    “Did that happen yet?”

    Apparently not.

  102. 102
    Dionisio says:

    Check this out:
    Transcriptomic signatures shaped by cell proportions shed light on comparative developmental biology

    Article (PDF Available)?in?Genome biology 18(1)
    DOI: 10.1186/s13059-017-1157-7

  103. 103
    gpuccio says:

    Dionisio:

    Wow! You are really good at finding interesting articles.

    Just think: if all that complexity of process is implied to just get different sizes in two similar teeth, what can we expect for more complex differentiation processes at phenotypic level?

    The methodology of this paper is very interesting and original: trying to link phenotypic differences to the whole epigenetic scenario is indeed a very correct way to understand what really happens.

    Of course, a real understanding of what drives and controls these complex processes is still lacking… 🙂

  104. 104
    gpuccio says:

    Dionisio:

    We first wondered whether this pattern could be caused by specific or strongly biased genes that would mark a clear lower versus upper molar identity, as identified for early jaws [50]. A single gene, Nkx2-3, was specifically expressed in the lower molar and we found no gene specific for the upper molar, although the top upper gene, Pou3f3, was about ten times more expressed in the upper molar. If fact, when taking all samples from each kind of tooth in the large-scale dataset as replicates (so in total, eight replicates for upper and eight for lower molar), we found 1347 genes (out of 14,808) differentially expressed (“upper/lower DE genes,” adjusted P value?<?0.1), out of which only 83 show more than a twofold excess difference (see Additional file 2: Table S1). This included genes known for their role in molar or jaw specification (like Dlx5 and 6, Pou3f3, and two associated non-coding RNAs (ncRNA), 2900092D14Rik, 2610017I09Rik [50], Pitx1 [43]). We concluded that there were relatively few genes that were consistently biased with a fold change over 2 throughout stages. On a developmental point of view, however, these consistently biased genes were possibly sufficient to provide and sustain different orientations for upper and lower molar development.

    Are those consistently biased genes sufficient to explain the genomic signature that separates the upper and the lower tooth? To answer this question, we looked how far this genomic signature would resist the removal of differentially expressed genes. Removing the 83 above-mentioned genes had a marginal effect on the second axis of PCA (11.4% of variation explained instead of 12.9% with the 83 genes). In fact, the second axis of the PCA still separated the upper and lower samples and represented a significant amount of the total variation, even when all differentially expressed genes were removed: after removing 1347 DE genes that were found when the eight stages are taken as replicates, the axis that splits upper and lower tooth represented 9.3% of the total variation. Upper/lower DE genes can also be estimated taking time into account (DESeq2, adjusted P value?<?0.1), which is less stringent and resulted in 3155 DE genes: after removing these genes, the axis that splits the upper and the lower tooth represented 7.8% of the total variation. We concluded that the upper/lower transcriptomic signature was not only carried by sets of genes that are moderately to strongly biased throughout the developmental period, but also by more subtle gene expression differences in a very large number of genes.

    This is very interesting. 83 genes that are expressed in a strongly different way would seem more than enough to explain the difference between upper and lower molar in the mouse. And yet, they are not the answer. Part of the answer are a lot of minor differences in expression in a lot of other genes, differences that only a global statistical approach like Principal Component Analysis can reveal.

    Epigenetic regulation is like that: a general, pervasive, extremely balanced program for each different situation.

    A miracle? From a programmer’s point of view, I would definitely say yes! 🙂

  105. 105
    Dionisio says:

    gpuccio @103:

    […] if all that complexity of process is implied to just get different sizes in two similar teeth, what can we expect for more complex differentiation processes at phenotypic level?

    That’s a very logical observation and question.

    The methodology of this paper is very interesting and original: trying to link phenotypic differences to the whole epigenetic scenario is indeed a very correct way to understand what really happens.

    I see your valid point. Agree.

    […] a real understanding of what drives and controls these complex processes is still lacking…

    Yes, perhaps that’s why we see the ‘junk of the gaps’ and the Neo-Darwinian ‘just so’ fairytale propaganda still going unchallenged in many academic circles.

    However, with the accelerated improvement of cellular & molecular visualization technology and the refining of the computer-based modeling techniques used by dedicated interdisciplinary research teams, we should see a growing avalanche of discoveries coming out of the numerous wet and dry labs, thus shedding light on the big picture we all are so eager to understand.

    Obviously, as some outstanding questions will get answered, new ones will be posed. But with every discovery the intelligence design paradigm will get strengthened further while the Neo-Darwinism will continue its fall into the trash bin where it belongs, remaining solely as a shameful historic reminder of what can happen when science is not done honestly, humbly, with open-mindedness, thinking out of wrongly preconceived boxes, avoiding gross extrapolations and misinterpretations of the available evidences.

    We’re told to test everything and hold only what is good.

    In this thread you showed how to do serious, honest, thorough research. I’m sure many readers here, including the anonymous onlookers/lurkers (7 times more than the number of posted comments) really appreciate it.

  106. 106
    Dionisio says:

    gpuccio @104:

    This is very interesting. 83 genes that are expressed in a strongly different way would seem more than enough to explain the difference between upper and lower molar in the mouse. And yet, they are not the answer. Part of the answer are a lot of minor differences in expression in a lot of other genes, differences that only a global statistical approach like Principal Component Analysis can reveal.

    I like the comprehensive way you have summarized it.

    Epigenetic regulation is like that: a general, pervasive, extremely balanced program for each different situation.

    That’s a very interesting way to describe it in few words.

    A miracle? From a programmer’s point of view, I would definitely say yes!

    Fully agree!

    Thanks.

  107. 107
    Origenes says:

    GPuccio: Sometimes darwinists seem to forget that not any function is good in a cell environment. Many “functions” are simply useless, or detrimental.

    Excellent crucial point.

    Suppose a DVD copy machine which produces a few random copy-errors every time it makes a copy. Suppose this machine makes 10 copies of a newly purchased functional Windows 7 DVD. Now remove this original DVD and repeat the imperfect copy process starting with functional second generation “mutated” copies (dysfunctional copies are removed from the process after testing). Next remove all second generation copies and repeat the copy process starting with functional third generation mutated copies. And so forth.

    Question: who of us would expect this imperfect copy process to be anything other than the degeneration of Windows 7 eventually leading to mutated copies which are, without exception, dysfunctional?

    And finally, if by sheer dumb luck random copy-errors produce some new functional code, who of us expects this new functionality to fit in? If some new activity stems from code produced by random errors, who would be optimistic? IOWs who would expect this new functionality to be integrated in Windows 7? Who of us expects versions of Windows 7 with improved functionality?

  108. 108
    gpuccio says:

    Origenes:

    The point that most functions, which could in principle be useful in some context, will be useless or detrimental in a specific complex system, like a specific cell of a specifi organism, is a very important one. It is a very strong counter-argument to the common pseudo-argument often made by darwinists, that NS is really special because it can select “any possible function”.

    The “any possible function” argument is, indeed, completely wrong. NS has extremely strong restrictions, and the main are:

    1) It can select only for those functions that are useful in that specific context: cell, organism, epigenetic scenario, and so on.

    2) The new function, moreover, must not only be potentially useful, but also well integrated in the context, so that it is really, practically useful. As yuou have so well emphasized.

    3) Finally, the new function must not only be useful in a general sense: it must be able to confer a detectable reproductive advantage, so that NS can act on it and fix it by negative and positive selection. This is very important, because many seem to forget it: any function, even if useful, is invisible to NS if it does not confer a detectable reproductive advantage, and in many cases even a detectable reproductive advantage will not be enough to fix the new trait.

    And it will be useful to remind that NS can act only when the new function is completely there, ready to work to confer the reproductive advantage. All the steps that precede that state are completely invisible to NS. Until such a function appears, all the rest is a random walk, and nothing else.

    With all these restrictions, we can safely state that Natural Selection is really powerless when functional complexity is implied: it cannot act on “any possible function”, but only on an extremely restricted subset of functions, and even that only when the function is completely there, and well integrated in the context.

    While I am very sure that the protein functional state is not dense in connected functions, I am of course even more sure, beyond any doubt, that it is not dense in naturally selectable, connected functions.

  109. 109
    Eric Anderson says:

    gpuccio @103:

    Just think: if all that complexity of process is implied to just get different sizes in two similar teeth . . .

    This is precisely one of the examples I was thinking about when I said @69:

    Finally, there are thousands upon thousands of biological functions and processes that we know exist and for which clear genetic instructions have not yet been identified — vastly more in fact, than what has thus far been identified. It follows as a matter of logic that either (a) a significant amount of allegedly-non-functional DNA will turn out to have function, or (b) the known functional DNA will turn out to have many more layers of multiple-functionality than currently thought. Or a combination of the two.

    I’m glad see someone has looked into the teeth at least.

    —–

    I like to give a couple of examples when people question how much there is yet to learn — two examples that they can quickly grasp from a personal, individual level: your teeth and your nose.

    There is this incredibly pervasive and naive concept in biology, in particular in the materialist strain of thought, that once you get some proteins floating around in the cell things just automatically come together by force of chemistry and physics to form wonderful, complex, functional systems. We’ve even had a few interlocutors on these pages argue vehemently for such a claim.

    It is simply false. Blatantly and obviously so. But we have to stop and think through the details in order to realize it.

    Here is the reality, an ongoing prediction from the design perspective: We will find that scarcely anything important happens in the cell by dint of pure chemistry and physics. Anything useful or important that we want to have occur must be carefully orchestrated, monitored, moderated, controlled.

    Yes, even something as “simple” as where you tooth grows and what size it is, or where your nose forms and how it is shaped.

  110. 110
    Origenes says:

    GPuccio: … it [natural selection] cannot act on “any possible function”, but only on an extremely restricted subset of functions, and even that only when the function is completely there, and well integrated in the context.

    When we look at Swamidass’ statement:

    “…. the pervasive observation of multifunctional proteins suggests that functions are actually very close to one another and abundant.”

    we find that not only it is not true (Hayashi), but, moreover, the kind of function Swamidass is talking about is utterly irrelevant. What Swamidass needs to show is that fitting, complete and well integrated functions are ‘very close to one another and abundant’.

  111. 111
    gpuccio says:

    Eric Anderson:

    “Yes, even something as “simple” as where you tooth grows and what size it is, or where your nose forms and how it is shaped.”

    Absolutely:

    The origin of form still remains one of the great mysteries out there. Morphogens are certainly part of the answer, but just a small part.

    And the epigenetic approach is simply confirming what we already knew: that we really don’t understand how fomr, from whole body plans to the minuscule details, originates.

    I would like, in that regard, to quote the title of one of the pioneers of ID thought, the great italian biologist Giuseppe Sermonti:

    “Dimenticare Darwin. Perché la mosca non è un cavallo.”

    (Forgetting Darwin. Why a fly is not a horse.)

  112. 112
    gpuccio says:

    Origenes:

    “we find that not only it is not true (Hayashi), but, moreover, the kind of function Swamidass is talking about is utterly irrelevant. What Swamidass needs to show is that fitting, complete and well integrated functions are ‘very close to one another and abundant’.”

    OK,let’s wait for him to show that.

    But I am not holding my breath! 🙂

  113. 113
    Dionisio says:

    Clarification for the comment @90 & 92:

    Note that every Delta(x) must include all the developmental changes to the associated GRNs, signaling pathways and cascades, morphogen gradient formation and interpretation mechanisms, epigenome, epitranscriptome, etc. required to transform Dev(ca) to Dev(x), where x={d1,d2} according to every particular case.

    Once Dev(ca) and Dev(x) are precisely described, then it shouldn’t be a major issue to determine the corresponding Delta(x) for every descendant.

  114. 114
    Dionisio says:

    Eric Anderson @109:

    There is this incredibly pervasive and naive concept in biology, in particular in the materialist strain of thought, that once you get some proteins floating around in the cell things just automatically come together by force of chemistry and physics to form wonderful, complex, functional systems. We’ve even had a few interlocutors on these pages argue vehemently for such a claim.

    Yes, those are the same folks that would invest all their money to buy oceanfront apartments in the middle of Kansas or Siberia without questioning it.

    🙂

  115. 115
    gpuccio says:

    Friends:

    I suppose that I should really thank timothya.

    Apparently, he is the only one that has tried to criticize my post.

    As they say: “No critics, no party!”

    Well, thank you, timothya. Seriously, and from my heart.

  116. 116
    bill cole says:

    Origenes

    we find that not only it is not true (Hayashi), but, moreover, the kind of function Swamidass is talking about is utterly irrelevant. What Swamidass needs to show is that fitting, complete and well integrated functions are ‘very close to one another and abundant’.

    This is not consistent with what we see in cells especially the cell nucleus. The requirement is, proteins with unique binding capability or the transcriptional paths that regulate cell function would not be possible. If a JNK path protein starts to bind with a KRAS path protein the cell mis functions.

    The design of proteins is based on a sequence of amino acids defined in the 4 nucleotides of DNA. This is a sequence (the largest type of mathematical space) and it is possible to generate almost infinite diversity which is required for functioning living cells. Finding function through a random search not so much 🙂

  117. 117
    Dionisio says:

    gpuccio @115:

    where did you see that politely-dissenting interlocutor wrote about your article?

    I don’t see it. What’s the post #?

    BTW, the number of anonymous visits is over 7 times greater than the number of posted comments.

  118. 118
    gpuccio says:

    Dionisio:

    He made a generic objection at #16, to which I wnaswered at #18.

    Then, let’s say that he “asked for clarifications” about some little misunderstanding of the cladistics at #23, to which I answered at #25 , and again at #28, to which I answered at #29.

    After that he kept his peace.

    Not much, I agree, but there was nothing else (from our kind antagonists). So, thank you, timothya!

  119. 119
    Dionisio says:

    gpuccio,

    Yes, I see it now. I missed it because didn’t scroll back to the earlier posts. My mistake.
    Yes, that was nice of timothya to write objections and ask for clarifications in such a polite manner.
    Maybe other antagonists will notice it and do similarly?

  120. 120
    Dionisio says:

    Upright BiPed @5:

    I expect you may get caught up in cross-platform comments […]

    Dionisio @100

    Did that happen yet?

    gpuccio @101:

    Apparently not.

    would it matter?

  121. 121
    Dionisio says:

    Apparently when the discussion gets really scientific the politely dissenting interlocutors take time off?

    Only 4 politely dissenting comments out of 120?

    @16 answered by GP @18
    @23 answered by GP @25
    @28 answered by GP @29
    @30 answered by GP @32 (also answered by Origenes @34)

    Is that all?

    Did they run out of valid arguments?

    Did they ever have any?

    🙂

    Since this discussion was so interesting, it proves once more that the politely dissenting interlocutors may not add value to the threads?

  122. 122
    gpuccio says:

    Dionisio:

    A good summary.

    Now, just for the sake of it, I would like to propose a few simple questions to our “politely dissenting interlocutors” (as you call them), or, for what it is worth, to anyone interested.

    In the light of the methodology and the results presented here:

    1) Can anyone still defend the position that functional information does not exist, or that it is a vague, ill defined philosophical concept?

    2) Can anyone still defend the position that functional information cannot be measured in any practical way, or in any real-life context?

    3) Can anyone still defend the position that functional information, even if measured, is of no interest to the understanding of biological systems?

    Just to know. 🙂

    Because I am certain that at the first occasion, in different discussions, a lot of people will be ready to state exactly those positions, when it is necessary for them to defend some undefendable aspect of their neo-darwinian world view.

  123. 123
    Dionisio says:

    gpuccio,

    Excellent questions. And very easy to respond.

    Next time someone pops up in another discussion stating those positions they should be referred to your comment @122 here in this thread:

    http://www.uncommondescent.com.....ent-627784

  124. 124
    gpuccio says:

    Dionisio:

    “Next time someone pops up in another discussion stating those positions they should be referred to your comment @122 here in this thread:”

    I hope they will…

  125. 125
    kairosfocus says:

    GP, frankly the first question was answered by March 19, 1953 in Crick’s letter to his son, which recently sold for US$ 6 millions. An acknowledgement of its significance. The second and third were answered before that, as information was definitively put on the table in a quantified, functional context in 1948. In terms of specific metrics of functional information, those have been developed in recent years. The objections have represented selective hyperskepticism, not any responsible position, all along. KF

  126. 126
    gpuccio says:

    KF:

    Thank you for your precious intervention and historical clarification and perspective.

    Of course the concept of functional information is not new at all. My contribution has simply the aim to apply that old and well established concept in a systematic way, and to provide some tangible example of how useful that concept can be in biology. And, of course, to try to quantify specific instances of that functional information to add support to ID theory.

    With special thoughts to our “politely dissenting interlocutors” (at present rather latitant) who, certainly out of “selective hyperskepticism, not any responsible position”, insist in denial of the concept or of its measurement strategies.

    And, I am afraid, there are a lot of them…

  127. 127
    kairosfocus says:

    GP, I think your contribution is A1 grade. Just, I am amazed that we have had to go to this sort of length of belabouring the obvious. Imagine, objectors making objections in order to object, create further examples of the sort of functionally specific information they decry: instantly absurd. Then, the denial that we are looking at text in DNA simply tells me that they are desperate not to see what is plainly, Nobel Proize winningly there. That speaks saddening volumes on where we are as a civilisation today. KF

  128. 128
    gpuccio says:

    KF:

    Thank you for your kind words. Yes, it is sad to face such a denial of obvious truths.

    However, on the other hand, it is a joyous privilege to fight for them! 🙂

  129. 129
    Dionisio says:

    KF @127:

    Imagine, objectors making objections in order to object, […]

    Yes, that’s the undeniable sad reality. Thank you for your insightful comments here, which could serve as an interesting historical prologue to a technical paper GP could write in he future for many to enjoy reading.
    It’s depressing to see how much criticism is out there by those who wrongly claim that the ID paradigm lacks scientific substance, but just about 3% of the comments posted in this scientific discussion are from those critical voices. When those folks are given opportunities like this to present their arguments, their conspicuous absence raises some questions. Obviously, we know they lack valid serious arguments, but still they could politely present whatever argument they have.
    A couple of years ago I asked a very simple biology-related question to a Canadian biochemistry professor in this site. I’m still scratching my head trying to understand what could have possessed him to write such a pathetically wrong answer. I was looking forward to have an interesting discussion but was disappointed because the professor quit right away, saying that I did not ask honest questions. Denyse translated that to me from Canadian academic English to commoners’ jargon, but her explanation did not satisfy my curiosity. I’m still trying to figure out what went wrong then. I definitely respect that professor and thought I could learn quite a bit from a serious biology-related discussion with him, but unfortunately it turned sour and was aborted prematurely.
    Perhaps he quit because it would have been a waste of time for him to discuss biology issues with someone who publicly had declared that knows very little about that topic? Maybe.
    Does anyone recall that incident? It’s recorded in this site. Anybody can read it again.
    It’s quite different in the case of GP answering all my dumb questions, sometimes repeated questions, probably annoying questions too. 🙂
    Now, why is it that a Canadian doctor can’t stand such a discussion while an Italian doctor can?
    Maybe that’s because Hispanics and Italians have more in common? 🙂

  130. 130
    Eric Anderson says:

    gpuccio @22:

    2) Can anyone still defend the position that functional information cannot be measured in any practical way, or in any real-life context?

    OK, I’ll bite. 🙂

    Yes, there are ways to measure functional information — as long as we have recognized it as such in the first place. In other words, we can’t just throw math at a system and discover if we are dealing with complex specified information. But I agree that once we know we are dealing with such information (by recognizing meaning, purpose, function, etc.), then there are ways we can measure the level of complexity involved in how that information has been represented.

  131. 131
    gpuccio says:

    Eric Anderson:

    Fine!

    IOWs, you are saying that first we have to give a binary value to the function, and then measure the complexity linked to the presence of the function. That’s perfectly correct.

    In the specific case of my methodology, I define function rather indirectly. It could be more or less this:

    “Let’s define as functional parts common to two lineages the parts of a protein sequence that are enough functionally constrained to be conserved between the two different organism lineages, even if separated by a very long evolutionary split time (in the case of pre-vertebrates vs vertebrates, more than 400 million years).”

    Then, by effecting the alignment between the proteins in the two organisms, and getting an homology bitscore, we consider that bitscore as a satisfying measure of the complexity in bits linked to that functional definition, for that protein.

    IOWs if we have a bitscore of, say, 250 bits between a human protein and the best homologue in pre-vertebrates, then we say that the functional part of that protein common to the two lineages, defined as the part that is so functionally constrained that it can be conserved for more than 400 million years in both lineages, has a complexity of about 250 bits.

    The important point here, again, is our definition of the function whose complexity we are measuring. IOWs, we are not measuring the total functional complexity of a protein, but the functional complexity which is shared between two lineages through a long enough evolutionary separation.

    To give the idea in brief, I have used the term “human conserved functional information”. Which means exactly what I have explained here.

  132. 132
    bill cole says:

    Gpuccio

    2) Can anyone still defend the position that functional information cannot be measured in any practical way, or in any real-life context?

    I think this is the most difficult requirement. Without biological experiment how do we know all the possible sequences that are available to human beta catenin? You also cannot isolate this because a single mutation may work fine on its own but what if the APC protein has a single mutation that works with the wild type beta catenin but not with the mutant.

    So the functional information in a single gene is not isolated to that gene.
    To get a precise value is difficult but for purposes of estimation of the new information required to make evolutionary jumps, your work yields solid information.

  133. 133
    gpuccio says:

    bill cole:

    “To get a precise value is difficult but for purposes of estimation of the new information required to make evolutionary jumps, your work yields solid information.”

    That’s exactly my idea.

    I don’t think we need precise values here, but rather reliable approximations, that can allow us to see tendencies, and to understand the basic modalities of evolution of information.

  134. 134
    Dionisio says:

    gpuccio @111:

    The origin of form still remains one of the great mysteries out there. Morphogens are certainly part of the answer, but just a small part.

    And the epigenetic approach is simply confirming what we already knew: that we really don’t understand how form, from whole body plans to the minuscule details, originates.

    Well, there’s a distinguished exception: professor Larry Moran, who responded “Yes” to the question “Do you know exactly how morphogen gradients are formed?”.

    In the thread “Mystery at the heart of life” there are several references to research papers that cover this topic. Everybody is welcome to read all that and draw their own conclusions.

    However, the increasing flow of discoveries are shedding more light on the subject, revealing a very interesting control level with novel codes and the whole nine yard. Simply fascinating. But as some outstanding questions get answered, new ones are raised. Unending Revelation of the Ultimate Reality. (c)

  135. 135
    Dionisio says:

    gpuccio @91:

    Regarding the biological classification criteria being based on physiological, phenotypic or genetic parameters, you wrote this:

    I think they are based on the sum total of what is available. It is not a simple field, and experts are constantly debating about those things. Which is good.

    I suppose that the fossil record remains the foundation, but molecular data are a great contribution.

    Why isn’t it a simple field? What makes it difficult?

    What things are experts constantly debating? Why?

    How accurate are the times associated with the fossil record? How are they determined?

    How do the molecular data contribute to this field?

    Thank you.

  136. 136
    gpuccio says:

    Dionisio:

    Again, I am not an expert of these things.

    Fossils are useful, I suppose, to determine the chronology of events. We can trace some groups of organisms back at least to when the first fossils appear. That’s how we know of the Cambrian explosion, and of other important events in natural history.

    Fossils can be dated with some precision, I think, mainly according to the strata where they are found.

    Then there is the problem of classification, which obviously starts at the level of morhology, and uses data from genomics and proteomics. Molecular clocks can add information.

    I think it is obvious that it is not simple to try to reconstruct the natural connections of different species, and the chronology of their appearance on earth. Why should it be easy? Science is never easy.

    Data are sometimes contradictory, or incomplete. Theories are often shown wrong, and they have to be substituted. That’s the normal way science works.

    There is nothing wrong in that, provided that scientists really try to understand reality according to available data.

    The problem is when that does not happen any more. That’s when cognitive bias prevaricates available evidence.

    A bias is systematic error: not the error of human limitations, which is natural and often good, because in the long term it leads to truth; but rather the error of human arrogance, of the desire to explain things according to prejudice.

  137. 137
    Dionisio says:

    gpuccio @136:

    Thank you for extending your comments posted @91.
    I think you have satisfied my curiosity on this topic. At least for the moment. 🙂

    Now, on the last part of the comment @91, which was related to the comment @90 and later was followed by the comment @92, you wrote:

    Regarding you question about the equations, I think you are right, but how do you think we can set the equations, with so many components we still don’t understand?

    Which of the known splits you referred to in the illustration of your methodology in this OP do you think is closer to reach the state where they know the developmental process of the line that splits and at least one of the branches produced by the split, so that we can determine the changes that are required to go from one to another?

    Can we get there faster if we try it for biological systems that are closer to each other, like the cats and dogs?
    If cats and dogs share a common ancestor, how far are we from defining the required changes to get dogs or cats from their last common ancestor?

  138. 138
    gpuccio says:

    Dionisio:

    I think we are still distant from a sufficient understanding to do what you propose, even is only to explain how C. elegans and C. briggsae, two worms separated by about 100 million years of evolutionary distance, are almost identical morphologically and yet have big differences in their genome and proteome.

    As I have tried to say, morphology is still a mystery, however we look at it!

  139. 139
    Dionisio says:

    gpuccio,

    […] almost identical morphologically and yet have big differences in their genome and proteome.

    Ok, so perhaps this is one of the best candidates to reach that state mentioned @137, because they’re almost identical morphologically -and maybe physiologically too? That could mean that their developmental processes could be very similar.
    Also, since they’re much simpler systems than cats and dogs, their developmental processes Dev(x) should be much easier to characterize in details. Also their Delta(d) should be less exuberant. Right?

    It would be interesting to know if these are the best known developmental processes. That would mean that perhaps soon they could be the systems that could be used to resolve the equations @90, i.e. determine their Delta(d).

    I’ll see what I can find out there on this pair of ‘cousins’. Perhaps the evo-devo literature already has them well characterized?

    The Drosophila is mentioned lately along a close cousin (forgot the name now). Perhaps those well studied models could help too. Should take a look and see.

    Maybe should include some plants too? Perhaps there are easier examples.

    Please, let me know if you ever read anything that could help with this task. Thanks.

    Let’s start from this:

    https://www.researchgate.net/publication/6806848_Comparative_genomics_in_C_elegans_C_briggsae_and_other_Caenorhabditis_species

    https://www.researchgate.net/publication/6228314_Comparison_of_C_elegans_and_C_briggsae_Genome_Sequences_Reveals_Extensive_Conservation_of_Chromosome_Organization_and_Synteny

  140. 140
  141. 141
  142. 142
    gpuccio says:

    Dionisio:

    C. elegans remain probably the single model organism in Metazoa of which we know most. A lot of work has been done on it.

    Moreover, it’s definitely a simpler organism than say, Drosophila, which has been studied in detail too.

    Of the about 1000 cells in C. elegans we know almost everything. We know them one by one. And yet, this detailed knowledge remains tantalizing, because even in this “simple” model the main questions about development that you so consistently pose cannot, IMO, find any satisfactory answer.

    Organisms separated by about 100 million years are a good frame to study development.

    C. elegans – C. briggsae is a good start.

    Mouse – Human is obviously a well studied context.

    I would definitely suggest Hymenoptera, which have a similar evolutionary separation and three main evolutionary branches (bees, wasps, ants), different enough to be very intriguing.

    Cats and dogs are separated by a smaller time window, about 40 million years, and could be another interesting model.

    There is so much to understand, so much to research. My firm conviction is that a functional information based approach can really be a “guiding light” in exploring these issues.

  143. 143
    Origenes says:

    GPuccio @113

    Yes we can measure functional information and the funny thing is that evolutionists are unwillingly 100% on board with this idea. Indeed, those preserved shared sequences must necessarily be functional information. That’s the key of the argument.
    By adopting the hypothesis of common descent and pointing out those immense functional information jumps GPuccio destroys the Darwinian narrative.

    *crickets*

  144. 144
    Dionisio says:

    Origenes @143:

    Are you referring to GPuccio’s comments posted @112 instead?

  145. 145
    Dionisio says:

    gpuccio @142:

    There is so much to understand, so much to research. My firm conviction is that a functional information based approach can really be a “guiding light” in exploring these issues.

    Thank you for the information about the biological models that are better known and the comments on the state of affairs in the field.

  146. 146
    gpuccio says:

    Origenes:

    “Yes we can measure functional information and the funny thing is that evolutionists are unwillingly 100% on board with this idea. Indeed, those preserved shared sequences must necessarily be functional information. That’s the key of the argument.”

    Yes, that’s the beautiful part of the argument. It is based on premises that are fundamental for neo-darwinist thought.

    It’s a little like in Godel’s theorem: neo-darwinism cannot be at the same time complete and consistent. 🙂

  147. 147
    Dionisio says:

    Since activity in this interesting thread seems slowing down, here are a few minor observations:

    As of now, this thread shows
    1,178 visits – 146 comments posted = 1,032 “quiet” visits (perhaps some anonymous onlookers/lurkers too?).

    Over 7 times more “quiet” visits than posted comments?

    Just 4 politely dissenting comments, i.e. less than 3% of the posted comments were “kind of” antagonist (though seemingly confused, groundless and ineffective). Apparently all those 4 comments were from the same person and they all were posted within the first 30 comments.

    The conspicuous absence of politely dissenting comments is really suspicious. We see some of those folks very active (though sometimes behave like trolls) in other non-scientific threads and wonder if they simply dislike engaging in scientific discussions? Maybe they don’t like serious science? After all, the OP that started this thread is as scientific and technical as it can be.

    Most probably they just ran out of valid arguments, if they ever had any. Maybe that’s all folks.

    Just some thoughts.

    Thanks to GPuccio for starting this thread and for answering all the questions that were posted.
    Thanks to all the folks who commented here.

    Now let’s look forward to reading GPuccio’s next article (soon?).

    Y’all have a good day.

  148. 148
    gpuccio says:

    Dionisio:

    Thank you for the summary, and for the support.

    Yes, I am very satisfied of this OP and of the following discussion, except for the lack of any criticism from the other side.

    TSZ seems quiet too. (By the way, I noticed that the thread about Swamidass’paper is no more there… I wonder what the reason may be.)

    If we use a Boolean search syntax, I suppose we can say that:

    Dissenters NOT timothya == 0 🙂

    Should we say that my results presented here remain unchallenged?

    OK, that’s fine for me. But it’s a pity, not so much for the results themselves, but especially for the following discussion, which has been really interesting and stimulating.

    Thanks to you all. 🙂

  149. 149
    Eric Anderson says:

    TSZ seems quiet too. (By the way, I noticed that the thread about Swamidass’ paper is no more there… I wonder what the reason may be.)

    For the benefit of those of us who don’t frequent TSZ, what was the general thrust of the thread about Swamidass’ paper?

    Not defending his misconceptions, I hope?

  150. 150
    Dionisio says:

    gpuccio:

    Should we say that my results presented here remain unchallenged?

    Yes. That’s obviously the case.

    The same could be said about a number of comments posted in this thread.

  151. 151
    gpuccio says:

    Eric Anderson:

    I have not read the thread, just a couple of the last comments, but my impression is that commenters were not so kind with him. I could be wrong, however. Now, as far as I can understand, Swamidass’OP is no more there.

    Instead, a new OP by VJ Torley has appeared, titled:

    “Is it easy to get a new protein? A reply to Ann Gauger”

    It recycles many of the false ideas about which we have commented here (Szostak) or elsewhere. For the moment, I prefer not to comment again.

  152. 152
    Dionisio says:

    Eric Anderson:

    BTW, why so much attention to a webpage that apparently is not recognized even by Alexa? 🙂

    Yes, I know that Alexa’s recognition should not serve as a quality parameter, but it definitely raises some suspicions. 🙂

    The question is how serious that website really is. At least they seem quite weak in the science-related arena, don’t they?

    Anyway, I don’t have spare time to squander on senseless discussions, much less to visit other venues that seem unattractive to my palate. 🙂

    At one point I did a quick comparison -triggered by a comment someone made here referring to that website- between that and this UD site and the difference was abysmal. The results are available here in UD.
    Who knows? Make be that woke them up and motivated them to get better? Dunno. Haven’t checked since there.

  153. 153
    gpuccio says:

    Eric Anderson:

    Another sad revival at TSZ (in the discussion about functional protein space) is the infamous nylonase issue. For reference, I have discussed it in great detail here:

    http://www.uncommondescent.com.....on-part-1/

    See in particular my posts #11 and #21, and the following discussion.

    With the brilliant cooperation of Paul Giem (on our side) and of some of the most brilliant discussants on the other side, like Piotr and Mark Frank.

    Ah, the old good times when it was still possible to have a stimulating discussion with intelligent, serious and honest defenders on neo darwinian thought!

  154. 154
    Origenes says:

    SHAME on the materialists who display a complete lack of integrity and an enormous amount of cowardice by ignoring this thread.

    Should we say that my results presented here remain unchallenged?

    [gpuccio]

  155. 155

    Where’s Matzke? Where’s Moran? Where’s …

    Perhaps Liddle will show up with a simulation.

  156. 156
    gpuccio says:

    UB:

    Frankly, I would love to have back Piotr, Mark Frank, or Zachriel.

  157. 157
    gpuccio says:

    UB:

    I must say that I have dear memories of Elizabeth! Maybe not so much of her arguments… 🙂

  158. 158
    gpuccio says:

    UB:

    Should I become nostalgic for Alicia, too? Ehm, maybe not. 🙂

  159. 159

    Ah, yes. I remember arguing ineffectively with all of them. 🙂

    (I mentioned the names I did because they are specifically biologistss — except for Liddle — I only include her because she is so consistent and would never stoop to making claims that she could not back up. And if she did, she would certainly acknowledge it without prejudice. 🙂 ).

  160. 160
    mike1962 says:

    gpuccio

    Always a pleasure.

    Keep coming back. 🙂

  161. 161
    vividbleau says:

    Gp, I remember the thread well. I never did receive an answer from Mark Frank to my two questions. How do you empirically go about demonstrating “nothing” and furthermore how can one imagine “nothing”.

    MF

    Thanks for taking time out to respond. I too hope you are feeling better. I thought you did an excellent job in summarising your position. A few comments.

    We continue to muddle two propositions.

    (A ) Everything that comes into existence has a cause.

    (B ) It is self-evident that (A ) is true.

    I think that at the QM level (A ) is false which would entail (B ) is false. The evidence for this being that QM scientists have built robust models without causes that account for what we observe. This is generally accepted as evidence for something not existing – think phlogiston or ether.

    To say that A is false does not mean “something not existing” or that something comes from nothing. There indeed can be no evidence of nothing. Your examples of phlogiston or ether have the potential to be investigated as to whether they exist or do not exist, nothing cannot be investigated since it has no physical properties whatsoever.There can be no evidence of nothing. It is as I keep repeating beyond (meta) physics.

    Even if you are correct that QM models accurately reflect no causes that does not equate that something comes from nothing. No model can model nothing since there is nothing to model.

    Several people have commented that (A ) is true and maybe (B ) because something can’t come from nothing or words to that effect. I can do no more than repeat what I written many times above. I contend that it is at least possible and maybe true at the QM level that things sometimes just appear. They don’t “come from” anything. There is no “coming from” taking place. They are just absent one moment and present the next. I don’t understand why this is so hard to accept.

    I have no problem with the observation that “things sometimses just appear” The key word here is “appear” and if everyone just left it there I would have no problems with that. But you dont leave it there rather you take a meta physical leap that this means that things that are appearing exist from nothing. This is an unwarranted leap IMO.

    If you can imagine something then it is logically possible.

    And this has been one of my main points all along. Assuming you are correct about this( see VJT).If it is correct you have argued forcibly that it is not logically possible that something springs from nothing.Please imagine for all of us “nothing”

    Vivid

    Still waiting.

    Vivid

  162. 162
    vividbleau says:

    Late edit

    MF

    Vivid:”Thanks for taking time out to respond. I too hope you are feeling better. I thought you did an excellent job in summarising your position. A few comments.”

    MF: “We continue to muddle two propositions.

    (A ) Everything that comes into existence has a cause.

    (B ) It is self-evident that (A ) is true.

    I think that at the QM level (A ) is false which would entail (B ) is false. The evidence for this being that QM scientists have built robust models without causes that account for what we observe. This is generally accepted as evidence for something not existing – think phlogiston or ether.”

    Vivid: “To say that A is false does not mean “something not existing” or that something comes from nothing. There indeed can be no evidence of nothing. Your examples of phlogiston or ether have the potential to be investigated as to whether they exist or do not exist, nothing cannot be investigated since it has no physical properties whatsoever.There can be no evidence of nothing. It is as I keep repeating beyond (meta) physics.

    Even if you are correct that QM models accurately reflect no causes that does not equate that something comes from nothing. No model can model nothing since there is nothing to model.”

    MF: “Several people have commented that (A ) is true and maybe (B ) because something can’t come from nothing or words to that effect. I can do no more than repeat what I written many times above. I contend that it is at least possible and maybe true at the QM level that things sometimes just appear. They don’t “come from” anything. There is no “coming from” taking place. They are just absent one moment and present the next. I don’t understand why this is so hard to accept.”

    Vivid : “I have no problem with the observation that “things sometimses just appear” The key word here is “appear” and if everyone just left it there I would have no problems with that. But you dont leave it there rather you take a meta physical leap that this means that things that are appearing exist from nothing. This is an unwarranted leap IMO.”

    MF “If you can imagine something then it is logically possible.”

    Vivid: “And this has been one of my main points all along. Assuming you are correct about this( see VJT).If it is correct you have argued forcibly that it is not logically possible that something springs from nothing.Please imagine for all of us “nothing””

    Still waiting.

    Vivid

  163. 163
    gpuccio says:

    UB:

    Yes they are biologists. Maybe that’s the problem! 🙂

    Seriously, I have never discussed directly with them. Moran is an interesting discussant, I think. Matzke…

    OK, let’s be constructive: Liddle is a very honest person! 🙂

  164. 164
    gpuccio says:

    mike1962:

    “Always a pleasure.

    Keep coming back.”

    Thank you indeed!

    I will, I will…

  165. 165
    gpuccio says:

    vividbleau:

    Thank you for the comments.

    I think Mark is a very honest discussant, and a good thinker. He is precise, and patient.

    His personal style is probably a little “rigid” (compare with the – sometimes excessive – “flexibility in Zachriel, for example). However, I have discussed with him a lot of times, with great personal satisfaction.

    OK, sometimes he avoid some aspects of a discussion, but I think that he does not do that out of malice. probably, he just stay quiet when he has nothing new to say. Nothing bad in that.

    Regarding the discussion you quote (thank you for the formatting, it makes things much clearer! 🙂 ), I obviously agree with you.

    My take on the problem is quite simple:

    Well, maybe QM entails that some phenomenic manifestation can appear at certain times (as they say, from quantum void). Then, philosophically speaking, I would never say that it “comes from nothing”.

    Of course, it comes from the laws of QM.

    Which, definitely, are not “nothing” (see the amount of complex mathematical concepts that are necessary to just start describing them).

  166. 166
    vividbleau says:

    GP I too think very highly of Mark. He was always respectful towards me. I found him to be as you say an honest discussant.

    GP :”Which, definitely, are not “nothing” (see the amount of complex mathematical concepts that are necessary to just start describing them).”

    As soon as one starts describing what nothing is don’t you think that pretty well shows how absurd that position is? To describe what nothing is is tantamount to admitting it is something. Game over. I mean Krause wrote a whole book about nothing. There sure was a hell of a lot of something describing what nothing is. Seriously Try to imagine nothing, we can’t because we always think of something which is the opposite of nothing. I would go one step further and say that “nothing” is inconceivable.

    Vivid

  167. 167
    gpuccio says:

    vivid:

    ” I would go one step further and say that “nothing” is inconceivable.”

    I agree.

    Of course, there are minor meanings where the word has some specific role in human reasoning. For example, in set theory we can define the empty set as a set that contains “nothing” (in the sense of “no objects”). But those are relative meanings, in well specified contexts.

    But if we are asked to conceive “nothing” as the “absence of any entity of any kind”, then I would say that’s really beyond human thought and imagination.

  168. 168
    Dionisio says:

    gpuccio @163:

    Moran is an interesting discussant, I think.

    Yes, agree. Interesting indeed. 🙂

    He wrote that he won’t discuss biology with me because I don’t ask honest questions. Who knows what he meant by that? 🙂

    It didn’t help that I asked the questions very respectfully and even admonished some folks who apparently don’t like him and were calling him names (they changed a letter in his last name).

    All that is publicly recorded in this website, available to anyone upon request.

    Yes, he’s an interesting discussant indeed. 🙂

    @129 I wrote:

    It’s depressing to see how much criticism is out there by those who wrongly claim that the ID paradigm lacks scientific substance, but just about 3% of the comments posted in this scientific discussion are from those critical voices. When those folks are given opportunities like this to present their arguments, their conspicuous absence raises some questions. Obviously, we know they lack valid serious arguments, but still they could politely present whatever argument they have.
    A couple of years ago I asked a very simple biology-related question to a Canadian biochemistry professor in this site. I’m still scratching my head trying to understand what could have possessed him to write such a pathetically wrong answer. I was looking forward to have an interesting discussion but was disappointed because the professor quit right away, saying that I did not ask honest questions. Denyse translated that to me from Canadian academic English to commoners’ jargon, but her explanation did not satisfy my curiosity. I’m still trying to figure out what went wrong then. I definitely respect that professor and thought I could learn quite a bit from a serious biology-related discussion with him, but unfortunately it turned sour and was aborted prematurely.
    Perhaps he quit because it would have been a waste of time for him to discuss biology issues with someone who publicly had declared that knows very little about that topic? Maybe.
    Does anyone recall that incident? It’s recorded in this site. Anybody can read it again.
    It’s quite different in the case of GP answering all my dumb questions, sometimes repeated questions, probably annoying questions too. 🙂
    Now, why is it that a Canadian doctor can’t stand such a discussion while an Italian doctor can?
    Maybe that’s because Hispanics and Italians have more in common? 🙂

    http://www.uncommondescent.com.....ent-627801

  169. 169
    Armand Jacks says:

    O@154:

    SHAME on the materialists who display a complete lack of integrity and an enormous amount of cowardice by ignoring this thread.

    Does that mean that I am not a coward and have integrity?

  170. 170
    timothya says:

    Upright Biped @159:

    “Ah, yes. I remember arguing ineffectively with all of them. ????

    (I mentioned the names I did because they are specifically biologistss — except for Liddle — I only include her because she is so consistent and would never stoop to making claims that she could not back up. And if she did, she would certainly acknowledge it without prejudice. ???? ).”

    Do you really mean that you argued ineffectively? If so, what did you learn from the experience?

  171. 171
    Dionisio says:

    Armand Jacks @169:

    Have you ever publicly claimed that the ID concept or proposition is not scientific or that this UD website is poor in scientific discussions?

    Do you agree with gpuccio’s OP and follow-up comments in this thread?

    If your answer to the first question is NO and you answer YES to the second question, then I think Origenes’ statement @154 does not concern you.

    Perhaps one could argue that Origenes should have specified (narrow down) in more details what kind of materialists his statement referred to. Maybe some materialists are neutral regarding the ongoing biology-related debates and don’t express any public opinion about ID or this website. I don’t think Origenes’ comment @154 refers to them.

    Perhaps Origenes was referring to those folks who claim this site is poor in scientific debates and/or ID is not scientific.

    The OP for this thread is as scientific as it can be.

  172. 172
    Dionisio says:

    timothya @170:

    Upright Biped should answer himself, but I assume he realized those debates were (and usually are) a waste of precious time. That’s why I try to avoid them, though sometimes I mistakenly engage in them.

  173. 173
    timothya says:

    Dionisio @172:

    “Upright Biped should answer himself, but I assume he realized those debates were (and usually are) a waste of precious time. That’s why I try to avoid them, though sometimes I mistakenly engage in them.”

    Yes, perhaps you should not presume to read someone else’s mind. In any case, your “waste of precious time” presumably explains your contributions to this thread:

    http://www.uncommondescent.com.....rt-of-life

    Forgive me, but it is to laugh.

  174. 174
    gpuccio says:

    Dionisio:

    About Moran, what I meant is that at least he is smart. 🙂

  175. 175
    gpuccio says:

    Armand Jacks:

    I don’t know if you are a materialist, and frankly I don’t care. But I am certainly happy to assume the best about your integrity and courage.

    I have never had, I think, the pleasure of discussing with you. Any contribution you may like to give about this discussion is certainly welcome.

    As you invited me to submit the content of this OP to a peer reviewed journal, I suppose I can ask you: if you were my peer-reviewer, what would you say? If you like, of course.

    By the way, have you ever tried to use R? It’s a great resource indeed. I use it (in a Windows environment), and use the R Commander package as a basic graphic interface.

  176. 176
    gpuccio says:

    timothya:

    No reasons to be hostile.

    Any scientific contributions from you to the discussion here are welcome.

  177. 177
    gpuccio says:

    Dionisio:

    Be sure that your contributions to the “Mystery at the heart of life” thread are greatly appreciated. By me, at least. 🙂

  178. 178
    Dionisio says:

    timothya @173:

    Forgive me, but it is to laugh.

    Yes, I forgive you, though on the recipient’s end the forgiveness is effective only if you truly repent. On my end it’s effective immediately.

    BTW, I’m glad that thread makes you laugh. I’ve heard it makes some Neo-Darwinian folks kind of anxious, because it reminds them how fast they’re running out of strong arguments to support their ‘just so’ stories. Ironically, the bad news for them come mostly from research labs unrelated to ID.

  179. 179
    gpuccio says:

    Dionisio:

    “Ironically, the bad news for them come mostly from research labs unrelated to ID.”

    How true! 🙂

  180. 180
    Dionisio says:

    gpuccio @177:
    I know you appreciate the references to research papers more than most people in this site. Also you understand them better than most folks here. That’s sufficient reason to keep posting more references.
    You’ve written some of the most insightful and encouraging comments in that thread. I’ve only posted references to papers written by other people, hence my contributions are practically insignificant.
    That thread is not popular by any measure. However, despite being unattractive to most people (including timothya), in the 27 months since its creation by News it has received 167 anonymous visits per month. Not bad for a boring nerdy thread. 🙂

  181. 181
    Dionisio says:

    gpuccio @174:

    Yes, I think so too. And most probably that professor knows more biochemistry and biology than I’ll ever learn. It was disappointing that he aborted our incipient discussion and shutdown any hope to give it try another time. I was looking forward to learning quite a few things from a Canadian professor at a prestigious university. Apparently that potential discussion wasn’t interesting to him because I wouldn’t be able to provide any new information in his area of expertise. The scientific knowledge in that discussion was expected to flow mostly out of him, but probably many readers could have benefited from his willingness to share his vast scientific knowledge with the rest of us publicly. That would have been encouraging and commendable. Unfortunately that didn’t happen.
    I wonder what went wrong then. Perhaps only the professor could explain it, but maybe he’ll never reveal it to us?

  182. 182
    gpuccio says:

    Dionisio:

    Eh, we have to be patient with professors. They are not like normal people… 🙂

    Seriously, I think the problem is that biologists, however smart, are in a really uncomfortable position: they have to pretend they can explain what they cannot explain, and they have to defend a theory that cannot be defended, but that almost everyone believes to be true.

    Frankly, I am happy that I am not in their shoes. 🙂

  183. 183
    Dionisio says:

    gpuccio:

    […] the problem is that biologists, however smart, are in a really uncomfortable position: they have to pretend they can explain what they cannot explain, and they have to defend a theory that cannot be defended, but that almost everyone believes to be true.

    What you just wrote describes the situation so well, that I will quote it again in the future.
    Thanks.

    Yes, agree that it shouldn’t be pleasant to be in their situation, which is getting worse with every new discovery.

    Poor things. We should feel compassion for them.

  184. 184
    Origenes says:

    gpuccio: Eh, we have to be patient with professors. They are not like normal people… 🙂

    We all know that Larry Moran is a huge fan of the junk-dna hypothesis. I once posed the question:

    If most of our genome is junk, then where is the information stored for the (adult) body plan? Where is the information stored for e.g. the brain? And where is the information stored for how to build all this?

    Here is Moran’s answer:

    Larry Moran: …. experts do not see a need to encode body plans and brain in our genome …

  185. 185
    gpuccio says:

    Origenes:

    Not even an expert brain? 🙂

    Moran, if I understand him well, is a huge fan of the theory that all the novelty (or almost all) in humans vs chimps is neutral variation, fixed by random genetic drift.

    So, we already have so little novelty in the human genome that it would be difficult to explain the differences in humans even if all of it were extremely functional. But no, according to Moran it’s exactly the amount of neutral variation that we can expect.

    Conclusion? Maybe human and chimps are exactly the same. Humans are probably only chimps suffering from narcissistic disorder, and convinced that they are superior for some cryptic reason.

    And Moran is probably convinced that he is superior to all the rest… 🙂

  186. 186
    gpuccio says:

    Origenes:

    Ah, but of course there are the HARs. Couple of hundred non coding regions, a few hundreds nucleotides each. Of course that’s enough to explain human nervous system.

    You know what is the most depressing aspect of Moran’s statement:

    “experts do not see a need to encode body plans and brain in our genome”?

    That it is simply and dramatically true!

  187. 187
    Dionisio says:

    gpuccio @185:

    Humans are probably only chimps suffering from narcissistic disorder, and convinced that they are superior for some cryptic reason.

    That’s one of the funniest statements I’ve read lately.

    But unfortunately it could be true. 🙂

    After all it has been demonstrated that humans and chimps share 103% of their genes. Well, I forgot the exact number, but it doesn’t matter, it doesn’t have to be exact, does it? 🙂

  188. 188
    Dionisio says:

    Origenes @184:

    I think the problem is that you didn’t ask an honest question. 🙂

    Next time try to ask honest questions. Maybe then you’ll get the right answer. 🙂

    I made the same mistake. I asked this extremely dishonest question:

    “Do you know exactly how morphogen gradients are formed?”

    The professor answered “Yes.”

    We could double check with Denyse, but maybe in Canadian English “dishonest question” means “tricky question”?

    Apparently the dishonest (tricky) part of my question was the word “exactly” embedded in the text in a kind of stealthy-subliminal way. 🙂

  189. 189
    gpuccio says:

    Dionisio:

    “Apparently the dishonest (tricky) part of my question was the word “exactly” embedded in the text in a kind of stealthy-subliminal way.”

    Of course, you should have bolded it!

  190. 190
    Dionisio says:

    gpuccio:

    Maybe that was my error. I should have bolded it, so that the professor could see it. BTW, can his students do the same, i.e. claim that his exam questions were dishonest (tricky) because some words were not bolded? 🙂

    Anyway, the whole show started with this introductory lesson on referring to ID and to a fellow Canadian lady in very respectful terms. See the comments posted @3 and @4 here:
    http://www.uncommondescent.com.....ent-584124

    Later this comment by DTZ @46 referred to my challenge, which paralleled professor Tour’s challenge, but from the perspective of a non-scientist:
    http://www.uncommondescent.com.....ent-584216

    Here’s my response @64:
    http://www.uncommondescent.com.....ent-584272

    DTZ responded @66:
    http://www.uncommondescent.com.....ent-584299

    Here the professor addressed me directly @69:
    http://www.uncommondescent.com.....ent-584320

    Here I responded @91:
    http://www.uncommondescent.com.....ent-584389

    Here the professor responded @94:
    http://www.uncommondescent.com.....ent-584416

    I didn’t expect my challenge to be taken seriously by a scientist of that caliber. That was a nice present I got that day! 🙂

  191. 191
    Dionisio says:

    #190 addendum

    That post by DTZ @46 was quite provocative, urging the professor to teach the ID folks a hard lesson by punishing the rebellious uneducated guy who had posted that insolent challenge to the Neo-Darwinian establishment:

    46 DTZ October 23, 2015 at 1:42 pm

    Dear Professor Moran,

    I think I see your point, but perhaps a more effective way to prove it is to show the alleged ‘challenge’ one of their folks posted here:
    http://www.uncommondescent.com.....ent-582669
    is not a challenge at all.
    The guy who wrote that comment admitted he’s not a scientist. It should be easy for someone with your academic credentials and scientific knowledge/experience to show there’s nothing challenging about their questions.
    Actually, if you do so, you may shutdown their website completely, or at least future visitors would see what’s going on.
    Wouldn’t this approach work better than engaging in non constructive arguments with the ID folks?
    Had I had a fraction of your scientific knowledge I would have shut up that guy who issued the alleged ‘challenge’ in the above link.
    Thank you.

    http://www.uncommondescent.com.....ent-584216

    The reply to DTZ’s provocative comment was posted @64 the following day:

    Regarding the link you posted @46, I don’t think that answering those and other follow-up questions would necessarily shutdown this website. But it definitely could provide to the mentioned professor and his comrades the credibility they all currently lack so badly.

    However, better don’t hold your breadth while waiting for the mentioned professor or anybody else to dare accepting my invitation to seriously explain things and answering questions. I don’t expect that to occur anytime soon. They seem to lack what is required to do it.

  192. 192
    Dionisio says:

    #191 addendum:

    Looking back at that sequence of comments, now it’s obvious that my perception and expectations -as expressed @64- were proved wrong: apparently DTZ’s message persuaded the professor to move ahead and teach the ID folks a hard lesson by responding the insolent challenge posed by the uneducated rebellious guy. The professor’s reaction indeed took me by surprise. But I was glad, because it was a rare opportunity where we could have a potentially informative discussion with a professor willing to share publicly his vast knowledge of biochemistry and biology. Soon after that my expectations were proved wrong again. 🙁

  193. 193
  194. 194
    gpuccio says:

    Dionisio:

    Thank you for summarizing that interesting discussion.

    I will summarize it even more.

    1) Nobody knows how morphogenesis is controlled and guided.

    2) Moran is no exception to that.

    3) “Experts” are no exception to that.

    4) However, according to Moran (and, unfortunately, he is probably quite right): “experts do not see a need to encode body plans and brain in our genome”

    5) You and I, and probably some more sensible people, do see that need.

    6) So, it seems, the problem is not about what we know, but about what we see as a need.

    Now, I notice that Moran says:

    “experts do not see a need to encode body plans and brain in our genome” (emphasis mine)

    OK, that can mean two very different things:

    a) Experts do not see a need to encode body plans and brain in our genome, but they think that body plans and the brain are encoded elsewhere

    OR

    b) Experts do not see a need to encode body plans and brain anywhere.

    I will not ask Moran what he really meant, because I think it unlikely that he would respond. So, I can only guess.

    I would say that he means b). Why? Because, if he means a), I could probably partially agree, and that is a rather unlikely situation, IMO.

    Now, a) just means that the procedures are encoded elsewhere. That is probably true, at least in part. That “elsewhere can still mean two different things:

    a1) At some epigenetic level, that we can imagine

    a2) In some other way, that at present we cannot even imagine

    Well, I believe that all of that is true. The procedures are encoded in the genome, both at the level of proteome (see my OP here, for that) and at the level of non coding DNA (Ouch! Moran will not like that). And they are also encoded at many epigenetic levels. And they are also encoded at other levels that at present we cannot imagine.

    But there is one certainty, for me: they are encoded somewhere.

    Because, you see, most neo darwinists would rather go with b): they really believe that those things are not encoded anywhere.

    Now, while you and I certainly find that idea completely absurd, let’s try to understand what they think.

    The best, and most honest, admission about that, in my memory, was made by Piotr, some time ago, in a discussion that was exactly about the procedures for cell (and tissue, and organ, and body) development. He said, if I remember well:

    “I think it’s just the memory of what worked”.

    OK, that’s a very honest statement of a neo darwinian perspective. But, as it is honest, it includes a precious little word: memory.

    Now, you and I, having some love for informatics and programming, know all too well that “memory” is not a vague concept.

    Memory of information must be stored to survive and be available. And that requires, in our human experience, some storage medium. Usually some physical (and often expensive) storage medium.

    IOWs, no memory storage medium, no party.

    So, I would like to ask Piotr (if he still reads this blog, that is unlikely), or Moran (if he likes to answer, that is unlikely), or anyone else:

    Where and how are the procedure for cell (and tissue, and organ, and body) development stored?

    Because, you see, they are certainly available in some way, otherwise how could the embryo of any organism generate the full body?

    I suppose that the most likely argument of any neo darwinist, at this point, would be that those procedures must, after all, be very simple. A few HARs, a few hundred, at best a few thousand, nucleotides, and the deed is done.

    Done? The human body plan? The human brain and nervous system? The whole immunology network? And so on, and so on?

    You and I, having some love for informatics and programming, know all too well a very basic truth: very simple programs require some limited memory to be stored, but very complex programs require a lot of memory.

    So, is the information for human brain really so simple? Is it like squeezing, say, Windows 10 in 1-2 KB at most?

    OK, we know that the biological designer must be very good, but so good?

    Ah, but I forgot: neo darwinian evolution can do practically anything: even miracles, provided we don’t call them miracles! 🙂

  195. 195
    Dionisio says:

    gpuccio,
    I like your detailed description of the state of affairs in this business. You left no room for speculation.
    Yes, there must be a reasonable precise explanation for the processes that lead from a zygote to a complex multifunctional biological system. Some parts of that explanation are known, others are speculated or guessed at this point, but could be known tomorrow.
    What we know points to a designed system. What we don’t know does not point to anything, but when it will be known then we’ll see what it will point to. I believe it will point to a designed system, but let’s wait and see the facts when available.
    Ah, yes, as you said, neo darwinian evolution can do practically anything: even miracles, provided we don’t call them miracles! Yeah, right! 🙂
    Over a year ago someone I know consulted some scientists working on biology research and they told him that they still don’t know exactly what determines the morphogen source locations, their activation and deactivation timing, their production rates, the kind of morphogen that should be produced in every situation, etc. Let’s remember that the formation of the morphogen gradient should be done in such way that the cells to be affected should interpret the right information in the right location at the right time (spatiotemporally).
    Work in progress… stay tuned.
    But I’m confident that when the outstanding questions will be answered and the unknowns resolved, we’ll be in front of designed systems.
    That consultation occurred long after this aborted discussion with the Canadian professor. And those are scientists working on that stuff. They even said that the posed questions were at the core of their research. It can’t get closer to the topic than that.
    So how come the scientists working on morphogenesis admitted their lack of knowledge but the Canadian professor answer Yes to the question of absolute knowledge?
    But now we know that it was my fault, because as you well indicated, I should have bolded the word “exactly” but I didn’t.

  196. 196
    Dionisio says:

    gpuccio @194:

    The procedures are encoded in the genome, both at the level of proteome (see my OP here, for that) […]

    see my OP here? Link?

  197. 197
    gpuccio says:

    Dionisio:

    I meant this OP.

    The huge modifications in the vertebrate proteome are obviously linked to the novelties in the vertebrate body plan.

  198. 198
    Dionisio says:

    gpuccio,

    Oh, what was I thinking about? 🙂
    Thank you for waking me up. 🙂

    Yes, that makes sense. The information jump at the center of your OP in this thread seems like a required important component of the overall developmental Delta(vertebrate).

  199. 199
    gpuccio says:

    Dionisio:

    “The information jump at the center of your OP in this thread seems like a required important component of the overall developmental Delta(vertebrate).”

    Absolutely! 🙂

  200. 200
    Dionisio says:

    Just wanted to post the comment @200!
    Yes! Did it!

  201. 201
    gpuccio says:

    Dionisio:

    By the way, let’s comment some more on this interesting issue of development, always in the light of the results presented in this OP.

    Vertebrates are considered as a subphylum of chordates: chordates with backbones.

    So, in a sense, the basic body plan is set up in chordates, with the appearance of the notochord, and other features.

    As we know, phyla correspond to basic body plans. But, strangely enough, they all appear very “suddenly”, during the so called “Cambrian explosion” (approximately 541 – 520 million years ago).

    We know well all the debates about that amazing event. Of course, neo darwinist have tried their best to hypothesize that the explosion is not an explosion at all, and that the true information for all those new body plans was being “manufactured” more gradually during the previous times. And so on.

    But the evidence of the fossils remains what it is, and I don’t think that our “polite dissenters” have succeeded in explaining away the “almost miracle” of the Cambrian events.

    However, with vertebrates we are apparently observing an event slightly later than the Cambrian explosion itself. The emergence of a very important (for future developments) subphylum in the well established phylum of chordata.

    That allows to localize better the emergence of the new information, to somewhat later than the Cambrian, but anyway well more than 400 million years ago.

    Now, if we judge from the following natural history, it seems that the emergence of vertebrates was a very successful innovation: indeed, chordates not vertebrates are a rather small bunch of organisms today, while vertebrates are, in comparison, one of the main representative groups of animals, from many points of view, even if we don’t consider the side aspect that we, as humans, are part of it. 🙂

    So, it is rather interesting to observe, according to the data presented in the OP, that the transition to vertebrates was a very exceptional “jump” from the point of view of some specific functional information in the proteome, certainly the biggest step we can observe in the accumulation of human conserved protein information. In that sense, it is a much bigger step than the simple appearance of the phylum chordata, with the appearence of more than twice human conserved information (3,708,977 bits vs 1,685,550, not corrected for redundancy).

    If we want to make hypotheses about that interesting fact, we could probably reason that the new body plan of vertebrates includes at least two major innovations that will be very important in all the future natural history of that branch:

    1) Cephalization, and in particular the gradual development of the brain, and therefore of all new functiona connected to that

    2) Adaptive immunity, which appears for the first time in jawed vertebrates.

    Both these innovations have a common denominator: they are linked to the appearance and development of two very complex regulatory systems, both aimed to a very complex and nuanced interaction with the outer environment.

    IOWs, they are both, in different ways, complex systems that process information from the outer world.

    That is an important concept, because it bears a fundamental implication:

    If the bulk of the huge informational jump that appears in the vertebrate proteome is really linked to the premises for the development of the central nervous system and the brain and of the adaptive immune system, then it is perfectly reasonable to think that much of that new information must be strongly connected, as one can expect in any big and complex system that mainly processes information and reacts to it in very complex and nuanced modalities.

    Another way to say it is that, in that huge informational jump, a great part of the total information can be expected to be irreducibly complex.

  202. 202
    Dionisio says:

    gpuccio,

    very interesting reactivation of the discussion.

    […] the new body plan of vertebrates includes at least two major innovations that will be very important in all the future natural history of that branch:

    1) Cephalization, and in particular the gradual development of the brain, and therefore of all new functiona connected to that

    2) Adaptive immunity, which appears for the first time in jawed vertebrates.

    Both these innovations have a common denominator: they are linked to the appearance and development of two very complex regulatory systems, both aimed to a very complex and nuanced interaction with the outer environment.

    That’s an interesting area to explore for the developmental Delta(vertebrate) as a subphylum of chordates. You have managed to characterize some information increment in the proteome.

    Are these questions valid for each of the emerging details?
    How did such increment appear?
    What developmental processes did it affect and how?

    That could enhance tremendously the knowledge on the developmental Delta(vertebrate) added to Dev(chordates).

    Dev(vertebrate) = Dev(chordate) + Delta(vertebrate)

    Off topic: in the 5th paragraph the word manufactured seems misspelled?

  203. 203
    gpuccio says:

    Dionisio:

    “How did such increment appear?”

    This is still beyond our understanding. The only thing that is certain is that the necessary information was inputted by some conscious intelligent designer.

    “What developmental processes did it affect and how?”

    On this, I hope I can say something, probably in a future OP. Indeed, the database I have generated is a very good tool to quantitatively explore the evolutionary history of individual proteins, or of groups of proteins.

    “in the 5th paragraph the word manufactured seems misspelled”

    Corrected. That was not just a typo, but rather my italian that sometimes comes to the surface. The italian word is “manifattura” and “manifatturare”. 🙂

  204. 204
    DATCG says:

    Dioniso, I checked out the link:

    Mystery at Heart of Life

    Thank you… your effort is a good one. The findings only continue to grow as Darwinism and neo-Darwinism have failed to answer ENCODE. The inability to account for novel body plans in the past is far exceeded today as a result of Epigenetic findings and ENCODE.

  205. 205
    gpuccio says:

    DATCG:

    Yes, Dionisio has been doing a great work, with patience and goodwill, offering us a constant reminder of the “complex complexity” that is being daily discovered in biological science.

    His activity helps us focus on what should be at the center of our attention: how true science speaks volumes about ID theory, without ever uttering its name. 🙂

  206. 206
    Dionisio says:

    gpuccio @203:

    On this, I hope I can say something, probably in a future OP. Indeed, the database I have generated is a very good tool to quantitatively explore the evolutionary history of individual proteins, or of groups of proteins.

    That’s very interesting. I look forward to reading more on this from you. Thank you.

  207. 207
    Dionisio says:

    gpuccio:
    Regarding your comment on the Italian word ‘manifattura’ vs. the English equivalent ‘manufacture’, sometimes I have problems with English words that spell very similarly to but not exactly like their Spanish equivalents.
    I’ve probably mixed them more than once in my comments here in this website.
    In this case of the English word ‘manufacture’, the Spanish equivalent is ‘manufactura’. However, I think I’ve seen it written as ‘manofactura’ somewhere. Sometimes I’m not sure which way is correct.

    That’s a problem when one is exposed to several languages in various levels of intensity or duration, but one really doesn’t learn any of them. Some people think I know several languages, but really I don’t know well any language, maybe except Spanish, and maybe not even that. 🙂 I like them all, though.

    BTW, sometimes I write Spanish, Italian, Polish, Russian, German, Hungarian, French, Portuguese words intentionally, even though I don’t know those languages, but just because that’s a word that comes to mind, perhaps because I heard it in a particular context associated to certain situation. Welcome to globalization! 🙂

    For example, sometimes in lieu of ‘nonsense’ or ‘hogwash’ I may write the Polish word ‘bzdura’ or the Russian term ‘yerunda’ because I’ve heard them a number of times in similar situations and they sound kind of familiar. In the case of Russian language, this editor doesn’t seem to handle Cyrillic alphabet, hence I have to write a phonetic approximation. Also apparently certain Polish letters are not supported.

    When I read a paper that claims to explain something, but it really doesn’t seem to explain it, I may write ‘parole, parole, parole’ 🙂 Mina made that Italian expression very popular in my younger years and it has remained in my mind as a stamp for labeling certain speeches or articles that seem to lack what they claim to have.

  208. 208
    gpuccio says:

    Dionisio:

    The Latin word is manus (hand), so in this case English is nearer to the Latin source than Italian!

  209. 209
    Dionisio says:

    DATCG @204:

    Thanks for the comment.

    I’m glad you enjoy reading the references to select research papers. Join the club!

    Basically I just share references to research papers I find as part of my own research for a project I’m working on. I could have chosen not to share those references here, but it doesn’t cost much to do it, compared to the satisfaction of knowing that perhaps someone else would benefit from that action. It’s called the golden rule (proactive version): do onto others what you would like others do onto you. The most ancient version was passive, because it was mainly about not doing harm to others.

    Besides, some folks in this website, specially gpuccio, have encouraged me to share those references. Actually, they have shared references to very interesting papers too!
    It’s an interdisciplinary teamwork. 🙂

    You wrote:

    The findings only continue to grow as Darwinism and neo-Darwinism have failed to answer ENCODE. The inability to account for novel body plans in the past is far exceeded today as a result of Epigenetic findings and ENCODE.

    They fail to answer most fundamental questions.
    If you’ve read some of gpuccio’s OPs and follow up comments you may have noticed that the Darwinian theories in all their formulations and versions (neo-, modern synthesis, extended, post-whatever, etc.) seem to be between a rock and a hard place when it comes to explaining fundamental issues. Their situation should get worse in the future, as more discoveries are made at increasing rate, as we can see from the overwhelming number of research papers available lately.

  210. 210
    Dionisio says:

    gpuccio:

    The Latin word is manus (hand), so in this case English is nearer to the Latin source than Italian!

    That’s funny!

  211. 211
    kairosfocus says:

    GP, I headlined you at 194 and 201, here: http://www.uncommondescent.com.....challenge/ I think that needs to be separately focussed, it is so good. KF

  212. 212
    gpuccio says:

    KF:

    Thank you indeed! I am promptly joining the discussion there! 🙂

  213. 213
    gpuccio says:

    Dionisio:

    It seems that the main objection that I receive, both here and in KF’s new thread, is:

    “Why do you publish your things here?”

    Strange indeed.

  214. 214
    kairosfocus says:

    GP, don’t forget: we can shred that stuff elsewhere. Of course, if they could, it would be done here too. KF

  215. 215
    Dionisio says:

    KF,

    Of course, if they could, it would be done here too.

    Exactly. They simply lack serious arguments.

  216. 216
    gpuccio says:

    KF:

    So, where is all the shredding? 🙂

    Here everything is calm.

    On your thread, a very interesting discussion is going on, with a lot of visualizations and many very good contributions.

    From “our side”.

    From the other side, just the “goodwill” of rvb8 and some brief and cautious appearance of Bob O’H. If I am not wrong.

  217. 217
    Dionisio says:

    GP, is this somehow -at least slightly- related to the topic of your latest OPs?
    http://www.uncommondescent.com.....r-in-order
    Thanks.

  218. 218
    Dionisio says:

    GP @216:

    “goodwill” of rvb8

    That’s a funny “2 nice” way to refer to “trolling”

    🙂

  219. 219
    Dionisio says:

    GP @216:

    So, where is all the shredding?

    They ran out of power to start their toothless shredder.

  220. 220
    Dionisio says:

    GP, considering that this OP + following discussion is quite technical -hence less attractive to the general public than a Hollywood celebrity scandal (welcome to this world!)- it’s encouraging to see the below stats:
    As of now:
    1,709 visits vs. 219 posted comments.
    1,490 more visits than posted comments (probably including some anonymous onlookers/lurkers).
    Almost 7 times more visits without “footprints” than posted comments.

  221. 221
    gpuccio says:

    Dionisio:

    Yes, those are satisfying numbers indeed.

    To them we could safely add:

    Not one single criticism about the specific content of the OP, neither here nor in KF’s follow-up.

    Should I be happy or sad? 🙂

  222. 222
    Dionisio says:

    gpuccio:

    More stats:

    Popular Posts (Last 30 Days)

    Physics and the contemplation of nothing (2,546)

    The Woeful State of Modern Debate (2,374)

    The problem of agit prop street theatre (U/D: UC Berkeley… (2,089)

    A world-famous chemist tells the truth: there’s no… (1,941)

    The amazing level of engineering in the transition to the… (1,752)

    🙂

  223. 223
    gpuccio says:

    Dionisio:

    Yes, I am happy of some more visibility, because after all I really believe that the things presented and discussed here are worthwhile.

    Thank you for your constant support! 🙂

  224. 224
    Dionisio says:

    Still kicking? Up one position.

    Stats update:

    Popular Posts (Last 30 Days)

    The Woeful State of Modern Debate (2,410)

    FFT*: Charles unmasks the anti-ID trollish tactic of… (2,383)

    Physics and the contemplation of nothing (1,886)

    The amazing level of engineering in the transition to the… (1,783)

    The problem of agit prop street theatre (U/D: UC Berkeley… (1,699)

    Logically this tread may fade away from the ranking soon, leaving room for your next OP. 🙂

  225. 225
    gpuccio says:

    Dionisio:

    I am working at it! 🙂

  226. 226
    Dionisio says:

    gpuccio:

    Glad to hear that, but please take your time. No rush. Thanks.

    BTW, here’s another update. Up one position again.

    Popular Posts (Last 30 Days)

    FFT*: Charles unmasks the anti-ID trollish tactic of… (2,770)

    The Woeful State of Modern Debate (2,416)

    The amazing level of engineering in the transition to the… (1,795)

    The problem of agit prop street theatre (U/D: UC Berkeley… (1,585)

    Physics and the contemplation of nothing (1,571)

  227. 227
    Dionisio says:

    gpuccio:

    You’ve got two* in the hit parade? 🙂

    Popular Posts (Last 30 Days)

    FFT*: Charles unmasks the anti-ID trollish tactic of… (3,077)

    The Woeful State of Modern Debate (2,419)

    The amazing level of engineering in the transition to the… (1,809)

    A world-famous chemist tells the truth: there’s no… (1,363)

    GP on the Origin of Body Plans [OoBP] challenge (1,339)

    (*) one graciously provided by KF

  228. 228
    Dionisio says:

    #3 & #4 in the top 5

    Popular Posts (Last 30 Days)

    FFT*: Charles unmasks the anti-ID trollish tactic of… (3,220)

    The Woeful State of Modern Debate (2,419)

    The amazing level of engineering in the transition to the… (1,815)

    GP on the Origin of Body Plans [OoBP] challenge (1,348)

    A world-famous chemist tells the truth: there’s no… (1,309)

  229. 229
    Dionisio says:

    gpuccio:

    I thought you may want to take a look at this:

    Here we present an exception that supports the rule that the 20 human tRNA synthetases acquired new architectures to expand their functions during evolution.

    The new features are associated with novel, appended domains that are absent in prokaryotes and retained by their many splice variants.

    Alanyl-tRNA synthetase (AlaRS) is the single example that has a prototypical appended domain—C-Ala—even in prokaryotes, which is spliced out in humans.

    X-ray structural, small-angle X-ray scattering, and functional analysis showed that human C-Ala lost its prokaryotic tRNA functional role and instead was reshaped into a nuclear DNA-binding protein.

    Thus, we report another paradigm for tRNA synthetase acquisition of a novel function, namely, repurposing a preexisting domain rather than addition of a new one.

    Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS
    Litao Sun, Youngzee Song, David Blocquel, Xiang-Lei Yang and Paul Schimmel
    PNAS vol. 113 no. 50 14300–14305
    doi: 10.1073/pnas.1617316113

  230. 230
    Dionisio says:

    gpuccio:

    here’s more on the same paper:

    The 20 aminoacyl tRNA synthetases (aaRSs) couple each amino acid to their cognate tRNAs.

    […] 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms.

    AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans but with a wide sequence divergence.

    In human cells, C-Ala is also a splice variant of AlaRS.

    Crystal structures of two forms of human C-Ala, and small-angle X-ray scattering of AlaRS, showed that the large sequence divergence of human C-Ala reshaped C-Ala in a way that changed the global architecture of AlaRS.

    This reshaping removes the role of C-Ala in prokaryotes for docking tRNA and instead repurposes it to form a dimer interface presenting a DNA-binding groove.

    This groove cannot form with the bacterial ortholog.

    Direct DNA binding by human C-Ala, but not by bacterial C-Ala, was demonstrated.

    Thus, instead of acquiring a novel appended domain like other human aaRSs, which engendered novel functions, a new AlaRS architecture was created by diversifying a preexisting appended domain.

    Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS
    Litao Sun, Youngzee Song, David Blocquel, Xiang-Lei Yang and Paul Schimmel
    PNAS vol. 113 no. 50 14300–14305
    doi: 10.1073/pnas.1617316113

  231. 231
  232. 232
    gpuccio says:

    Dionisio:

    Thank you indeed!

    That’s exactly what I am trying to say.

    Proteins are reshaped, even when they conserve their main function throughout evolution.

    The reshaping can have many different meanings, but it is always a highly engineered result.

    Not only whole proteins, but even conserved domains are obviously reshaped in different species, and much of that reshaping is then conserved, and therefore functional.

    The 1.7 million bits of reshaping that took place to realize the proteome of the first vertebrates are traceable in the proteome in different forms: some proteins are almost completely new, and appear in cartilaginous fish practically for the first time, but many others are more or less drastically reshaped from existing homologues in pre-vertebrates.

    Conserved domains, which are often the least “reshaped” part of proteins, are also different in different species and contexts.

    Too much emphasis has always been given to functional similarities and to non functional differences, but the simple truth is that a very important part of the scenario has been repeatedly underestimated: the huge treasure chest of functional differences in similar things.

  233. 233
    Dionisio says:

    gpuccio:

    The subject of your research is very interesting indeed.

    When I saw that paper your research topic came to mind right away. Also I shared it with UB because it seems somehow related to his OP on biosemiotics.

    Also it is interesting to read “design for repurposing” in the title of that paper.

    Now the problem for some folks our there is to show how they would do all that protein “reshaping”: by trial and error? flipping coins? In any case they will have the advantage of knowing a priori the final shape, but still shouldn’t be too easy to figure it out.

  234. 234
    Dionisio says:

    gpuccio:
    A little old paper, maybe you already saw this:
    http://www.mdpi.com/1422-0067/16/3/6571/htm

    BTW, @233 in the first line of the last paragraph the word “our” should be “out” instead. My mistake. Fat fingers. 🙂

  235. 235
    gpuccio says:

    Dionisio:

    No. I did not know that paper. It seems extremely interesting and I will read it carefully.

    Thank you again for your constant attention and work. 🙂

  236. 236
  237. 237
    Dionisio says:

    gpuccio:
    Here’s another interesting article:
    http://www.pnas.org/content/ea.....4.abstract

  238. 238
    Dionisio says:

    Did the discussion here pause for lack of politely dissenting interlocutors?
    Where did they all go? Where are they?
    Don’t want to publicly admit lacking arguments?
    🙂

  239. 239
    Dionisio says:

    We look forward to reading gpuccio’s next article.

  240. 240
    EugeneS says:

    GP

    I have been on radio silence for some time. Looks like I missed an interesting OP and discussion. Catching up at my pace. Very interesting stuff. Thanks for this.

    In case you missed my OP:

    https://uncommondescent.com/intelligent-design/selensky-shallit-koza-vs-artificial-life-simulations/

  241. 241
    Dionisio says:

    Missing technical discussion threads like this.

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