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Information jumps again: some more facts, and thoughts, about Prickle 1 and taxonomically restricted genes.

Giuseppe Puccio
February 28, 2016
Genetics, Genomics, Intelligent Design
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My previous post about information jumps, based on the example of the Prickle 1 protein, has generated a very interesting discussion, still ongoing. I add here some more thoughts about an aspect which has not been really analyzed in the first post, and which can probably contribute to the discussion. I will give here only a very quick summary of the basic issue, inviting all those interested to check my first post: Homologies, differences and information jumps and the following discussion, amounting at present at more than 500 posts. So:

  1. Prickle 1 is an interesting protein, with rich functional properties, in general still not well understood.
  2. With reference to the human form, I have identified two different parts in the protein. A first part with 4 identifiable domains, and a second part with no identifiable domain. In the following discussion, I will continue to conventionally refer to those two sequences as “the red sequence” and “the blue sequence”, according to the colors by which I have marked them in the first post.
  3. The red sequence is present in all eukaryotes, starting from fungi, and shows increasing levels of homology to the human form.
  4. The blue sequence, as derived from the human form, is restricted to vertebrates. It is practically absent in all other metazoa.
  5. Just from the beginning of the vertebrate “tree”, the blue sequence shows a very high homology to the human form: about 600 bits of conserved information sequence between sharks and humans. IOWs, the blue sequence is highly conserved in vertebrates, just form the beginning.
  6. For all those reasons, I assume that the blue sequence is functional in vertebrates, and that its rather sudden appearance at the root of the vertebrate tree in a very specific form is a good example of an information jump in natural history.

OK. This is more or less the essence of the first post. The following discussion has touched many aspects, but I will not mention them all here, because I am confident that they will surface again in the discussion about this post. Now, I will try to sum up in advance what I am going to discuss in this second post, and then show the facts that support my ideas. So:

  1. In the first post, I have focused on the human form of the protein, and used its two sequences to measure different levels of homology in metazoa.
  2. The blue sequence in humans has been found to be highly conserved in vertebrates (and therefore almost certainly functional), and amazingly restricted to them.
  3. But what about other metazoa? The important point is: there is always a “blue sequence” in the Prickle 1 protein, in all taxa. But it is completely different from the blue sequence in vertebrates.
  4. The main point of this post is to demonstrate that the blue sequence in Prickle 1 is a good example of a functional sequence which is highly taxonomically restricted.

OK. I hope this is clear enough.

Just to start the discussion, let’s look at the Prickle 1 protein in tunicata, which are (with cephalochordata) the nearest neighbour of vertebrata: they are, indeed, chordates, but not vertebrates. If we compare the human Prickle 1 to the available data for tunicata, we find a few hits, all of which are relative to the red sequence. The human blue sequence, as already said. has no significant homology in tunicata. Now, let’s consider the hit with the human Prickle 1 protein in Ciona intestinalis, the reference organism for Tunicata. We have 456 bits of homology, a very good value, and the alignment is exclusively relative to the red sequence, IOWs, the domain sequence.

But what about the blue sequence in Ciona intestinalis? Is there a blue sequence, at all?

The answer is: yes, definitely. The Prickle 1 protein in Ciona intestinalis is 1066 AAs long, indeed a little bit longer than the human form (which is 831). And here too, like in the human form, the domain part is confined to the first part of the molecule. IOWs, we have a blue sequence which is about 712 AAs long, and is found after the conserved red sequence. Of course, that blue sequence has no homology to the blue sequence in vertebrates. We already know that, but just to check I blasted the two blue sequences one vs the other. The result? 20 bits, expect 0.30. IOWs, absolutely no homology.

So, the Prickle 1 protein in Ciona has its blue sequence, which is completely different from the one in vertebrates.

First question: is it taxonomically restricted?

You bet! If we blast that 712 AAs sequence against all existing organisms, including prokaryotes, we get only 3 hits: one is with itself, Prickle 1 in Ciona: 1447 bits, the identity value, IOWs, the maximum informational value of the sequence. The second is with Prickle 2 in Ciona, 1255 bits, an almost identity. The third is a partial but significant hit (107 bits, 2e-20) with a not well defined prickle protein in Molgula tectiformis, another organism in Tunicata.

That is certainly taxonomically restricted at its best!

What about Cephalochordata? Blasting human Prickle 1, we find only one protein in lancelet, “hypothetical protein BRAFLDRAFT_121177”. It seems to be a Prickle 1 protein, with the usual 497 bits of homology confined to the red sequence. The whole protein is 842 AAs. That means that here too there is a blue sequence after the domain part. I have blasted this sequence (366 AAs): only one significant hit, the identity hit with itself (751 bits). So, this sequence too is absolutely taxonomically restricted. Let’s go back in time. Human Prickle 1 against Cnidaria, the best hit is a protein in Hydra vulgaris, named “prickle-like protein 3”. Again, a good homology for the domain sequence: 423 bits (expect 4e-135). Again, the protein is much longer (724 AAs), and there is a blue sequence after the red one. Again, I have blasted it (359 AAs) against all organisms: 2 hits, the identiy (729 bits) and a good 297 bits homology with another cnidarian protein, “LIM-domain protein prickle” in Clytia hemisphaerica.

Taxonomically restricted? Yes.

OK, I think you get the idea. For the convenience of the readers, I have summed up a few results which I have obtained by following the same procedure as in the previous examples. Identifying human Prickle 1 homologues in some group of organisms, identifying the associated blue sequence in a representative of the class, then blasting that sequence against all living organisms, to evaluate how restricted it is. Here are some results:

 

Table

 

As everyone can see, different groups of organisms have different blue sequences, and those sequences are usually very much taxonomically restricted. For example, in Nematoda we have two completely different blue sequences in Trichinella species and in Caenorhabditis species.

Functional sequences?

OK, now the obvious question is: are these blue sequences functional? I strongly believe that we have reasons to think they are.

First of all, we have the example of vertebrates. The great number of sequenced genomes in vertebrates allows us to be sure that the blue part of the vertebrate sequence of Prickle 1 is highly conserved in practically all vertebrates, starting from cartilaginous fishes. That means high conservation for 400+ million years, an undeniable marker of negative/purifying selection and therefore of functional constraints. Those points have been discussed in depth in the previous posts and in the following discussion. Nobody has seriously denied that the blue sequence in the vertebrate Prickle 1 protein is functional.

What about other groups of organisms? Sometimes, the sequences are really very restricted, like in the case of Ciona intestinalis. Of course, in many cases that is also due to less biodiversity in the group, and/or lower number of sequenced genomes. So, it is much more difficult to ascertain how conserved each blue sequence is. However, let’s consider the following points:

  1. In most metazoa, with the exclusion of the simplest ones, and of unicellular eukaryotes, we find easily clear homologues of the Prickle 1 protein as we know it in vertebrates and humans. Of course, it’s the red part of the molecule, the domain part, which guides the identification, because of its good conservation in all those organisms.
  2. The rest of the molecule is different in different groups. Completely different, in most cases.
  3. However, in practically all homologues of Prickle 1,  there is always an accessory sequence, usually after the domain part (there are some exceptions, where it precedes the domain part).
  4. It seems quite reasonable that all, or almost all, these homologues of Prickle 1 in various species are functional, even if the function could be different from species to species, at least for the regulatory effects of the protein network where the Prickle 1 is included. It is also reasonable that the domain part has similar functions in different contexts, while the accessory blue sequence is more linked to the local context.

This is, IMO, a very reasonable explanation of what we observe. Can we support these ideas with some facts? Yes, we can. Giving as an acquired fact the functionality of the vertebrate blue sequence, let’s look at another interesting example: Hymenoptera.

 

OLYMPUS DIGITAL CAMERA

 

As we can see in our table, Hymenoptera are a large order of insects which includes, in its main suborder Apocrita, three different groups of organisms: very simply, wasps, bees and ants. Now, I will not go into details of the evolutionary history of Hymenoptera, but let’s just say that the split between these three groups is reasonably old enough, let’s say in the order of 100 million years, probably more. So, we have a scenario which is similar to vertebrates: wasps, bees and ants shared a highly conserved blue sequence, and the homology has been conserved for at least about 100 million years. That should be enough to infer functionality.

However, I have tried to support the inference of significant purifying selection acting on this blue sequence, performing a Ka/Ks ratio analysis on three sequences: a wasp (Polistes canadensis), a bee (Apis mellifera) and an ant (Camponotus floridanus).

Now, this is rather technical, but I will give just the main idea. A Ka/Ks ratio is essentially the ratio of non synonymous mutations to synonymous mutations. Synonimous mutations are those which do not change the aminoacid corresponding to the codon. Therefore, they are assumed to be neutral variation. If the value of the ratio is about 1, we can usually assume that the whole sequence is under neutral variation (there are as many mutations which change the sequence as mutations which do not change it, IOWs the sequence behaves like a non functional sequence). If the value of the ratio is sgnificantly lower than 1, we usually infer negative/purifying selection: IOWs, the sequence changes less than expected if compared to neutral variation, and therefore it is reasonably under functional constraints. If the value of the ratio is higher than 1 (a rather rare case), then we usually assume positive selection on the sequence: it changes more than expected. OK, that was as simple as I could say it.

I have computed the Ka/Ks ratio for the three above mentioned sequences (blue sequences in wasp, bee and ant). Here are the results:

Wasp – Bee:  Ka/Ks ratio = 0.09291813

Wasp – Ant:   Ka/Ks ratio = 0.05965076

Bee – Ant:  Ka/Ks ratio = 0.01145057

IOWs, the three different sequences seem definitely to be under purifying selection. Therefore, the sequences can reasonably be considered functional.

Another good example is the case of  C. elegans and C. briggsae. The blue sequence in these two species, even if not too long, shows very good conservation (311 bits), and it is also equally conserved  in other sequenced Caenorhabditis species (brenneri, remanei). Now, C. elegans and C. briggsae are two very similar little worms, but it is well known that they exhibit great genomic differences, and a rather old separation (maybe 100 million years again). Therefore, the conservation of the sequence in all known caenorhabditis genomes is rather telling.

So, what are the consclusions of this rather long and boring discussion? I will try to sum them up:

  1. In almost all Prickle 1 homologues in metazoa, a rather conserved domain sequence (the “red” part) is associated to an accessory sequence (the “blue” part) where no domain is recognizable.
  2. Those blue sequences are highly taxonomically restricted, and highly conserved in their restricted group of organisms, while they share almost no other homology with the rest of the existing proteome.
  3. There are very good reasons to infer that those sequences are functional, and that they probably contribute to the general function of the protein, and to its specificity in each group of organisms.
  4. So, while the red part of the molecule is a good example of function conserved through species, the blue part is a good example of function which varies completely between different groups of organisms, but is highly conserved in the gorup to which it is confined. IOWs. these blue sequences are a very good example of the concept which I have highlighted at the beginning of my previous OP:
  • 2b) (Differences between homologues) can be the expression of differences in function in different species and contexts

My final and brief point is that this kind of appearance of new de novo functional sequences in different groups of organisms, their strict taxonomical restriction and their high functional constraints are all very strong arguments for a design inference. But that, of course, will be the object of the discussion which, I hope, will follow. Including mass extinctions and other lucky events.  🙂

Comments
More on Prickle @1853-1855 here: https://uncommondesc.wpengine.com/intelligent-design/mystery-at-the-heart-of-life/#comment-615019 Dionisio
The whole genome sequence of C. autoethanogenum presented here-in represents a correction of the sequencing errors present in the previously published closed genome sequence generated primarily from an early iteration of PacBio sequencing technology. It was annotated via an automated pipeline and further curated manually to ensure the quality of annotation. This has resulted in the generation of the most accurate closed-genome sequence of the industrially relevant acetogen C. autoethanogenum to date and is an important step forward for academic institutions and industrial companies that wish to study and / or manipulate this organism for the purposes of high-value chemical production. Whole genome sequence and manual annotation of Clostridium autoethanogenum, an industrially relevant bacterium Christopher M. Humphreys, Samantha McLean, Sarah Schatschneider, Thomas Millat, Anne M. Henstra, Florence J. Annan, Ronja Breitkopf, Bart Pander, Pawel Piatek, Peter Rowe, Alexander T. Wichlacz, Craig Woods, Rupert Norman, Jochen Blom, Alexander Goesman, Charlie Hodgman, David Barrett, Neil R. Thomas, Klaus Winzer, and Nigel P. Minton BMC Genomics.16: 1085. doi: 10.1186/s12864-015-2287-5 http://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-015-2287-5
Dionisio
PSAT is a meta server that combines the results from several sequence-based annotation and function prediction codes, and is available at http://?psat.?llnl.?gov/?psat/?. PSAT stands apart from other sequence-based genome annotation systems in providing a high-throughput platform for rapid de novo enzyme predictions and sequence annotations over large input protein sequence data sets in FASTA. PSAT is most appropriately applied in annotation of large protein FASTA sets that may or may not be associated with a single genome. Protein Sequence Annotation Tool (PSAT): a centralized web-based meta-server for high-throughput sequence annotations Elo Leung, Amy Huang, Eithon Cadag, Aldrin Montana, Jan Lorenz Soliman and Carol L. Ecale Zhou BMC Bioinformatics 17:43 DOI: 10.1186/s12859-016-0887-y © Leung et al. 2016 http://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-016-0887-y
Dionisio
drc466: I have no idea if Ka/Ks can be applied to polimorphisms in one species. Maybe. However, it is absolutely correct that I have used it to detect functional conservation among different species. Which assumes common descent. gpuccio
Eric: I fully agree with you. Explanations must be explanations, not only new words to describe what we don't understand. An explanation based on consciousness (which is an observed fact) and design (which is an observed conscious process in ourselves) is an empirical explanation. Self-organization is a vague concept. If it is referred to observed processes, then we can safely say that those processes have nothing to do with the functional complexity we observe in biology, which is similar only to the functional complexity that we observe in human artifacts. As a generic concept, it is only bad philosophy. No explanation at all. The problem with what I call neo-neo darwinism is exactly that: they understand that neo darwinism does not work, but they cannot accept the only valid alternative: a consciousness centered theory of design. But it is absolutely true that there is no other game in town: only design and neo darwinism. One is true, the other is false. There are no other reasonable explanations. gpuccio
gpuccio, Sorry for the late reply. Thanks for taking the time to explain. Thanks to your excellent explanation, I realized that we are certainly talking apples and oranges here, as Ka/Ks is a measure of comparison between species that, as you say, assumes common descent is true, not a measure of mutation within a species where common descent is known to be true (i.e. we don't do Ka/Ks ratios on variations of bees, we do it on bees and wasps). Thanks again for the instruction. drc466
Anaxagoras @3:
Clearly, the cause of this different approach can be found in Denton´s commitment to a strong version of methodological naturalism. Personally I consider Gpuccio´s conclusion much more reasonable and convincing. Order (in the metaphysical sense of classical philosophy) always comes from an intelligent cause. Form is always prior to matter. Fine tuning is not a cause but just a condition for something to come about. Self organization, when talking of the emergence of non previously existent entities is a perfect oxymoron, no contingent being can be its own cause.
Denton should be commended for his efforts to shine a light on the problems with traditional evolutionary theory. I agree with you, however, that he seems to want to remain on the naturalistic side of the equation in terms of discussing causation. He seems to want the "respectability" of following a form of naturalism, while at the same time he is smart enough to realize that current naturalistic theories fall short. The real problem with the approach is that self-organization in all of its varieties is actually anathema to what we need for a living organism: copious amounts of contingent functional complexity and information rich structures. Self-organization in fact cuts against so much of what is needed in biology. Anyone who posits self-organization as an "explanation" for the origin of life or the origin of particular living organisms has no idea what they are talking about. Again, this isn't to say all of Denton's ideas should be thrown out. He has provided some very valuable contributions and interesting thoughts. In this particular area, however, his desperate desire to find some purely "natural" cause has led him down the garden path, casting about for explanations and grasping at straws. Eric Anderson
bFast: Hi, and welcome to the discussion. Yes, it seems that you have understood and summarized my ideas very well. Thank you! :) Regarding the problem of conservation, I will give you my point of view. I believe that the concept that conservation throughout very long periods of time implies function is a fundamental principle of any theory which tries to explain biological data. Indeed, neither neo darwinian evolutionary theory nor any form of design theory can make sense if we renounce that fundamental idea. Even if one does not accept common descent, and prefers to explain things merely by common design, still conservation would imply function, because how can you explain that a sequence is designed, many times, in exactly the same way? Only functional constraints can explain that simple fact. Now, let's go to histones. I suppose that you refer to this discussion by Cornelius Hunter: http://darwins-god.blogspot.it/2012/12/how-evolutionists-stole-histones.html which is based mainly on this paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326485/ Well, while the paper is certainly interesting, I must say that I strongly disagree with a general conclusion that it proves that the idea that histone conservation is due to very strong functional constraints of the whole sequence is wrong. Those experiments were done in yeast, and the results are only about short term viability of the cells. Now, one thing is to say that "whole chunks (of histones) can be deleted without destroying the resultant organism" (and, however, "whole chunks" is not exactly the right concept), another thing is to say that those modifications have no effect on the function, as expressed in terms of long term survival in natural history. I am absolutely convinced that the long term results of natural history are a much stronger fact than short term observations of gross viability in a lab, as far as true functional fitness is concerned. Histones are at the real core of epigenetic regulation in eukaryotes. It is certainly not a case that they are probably the most conserved sequence in all biological beings. I hope this answers your question. gpuccio
Hi gpuccio. This is the first time I have noticed this concept. May I reiterate the general thought in my own terms to see if I really understand. This "blue sequence", a rather large protein, is highly conserved in all vertebrates. Therefore, it is reasonable to assume that it came into existence in very nearly its current form sometime between the closest non-vertebrate, and the UCA of all vertebrates. However, that closest non-vertebrate has a "blue sequence" that is wildly different, and highly conserved within its tree branch. How did this occur? Back at the UCA of the tunicata and us, what was the "blue sequence" like? Was it very much like our "blue sequence", like the tunicata "blue sequence" or somewhere in between? If it was somewhere in between two wildly different sequences, how did it evolve so fast? How long did it have to evolve? The duration from the UCA of the vertebrate and tunicata, and the UCA of the most distant pair of vertebrates. That's not much time, I don't think. I think this is a serious challenge to the current paradigm. Oh, gpuccio, I appreciate that you said that you "assume" that this gene has an important function. I would caution that this is the theory talking. It appears that the histone H4 has weird stability that does not stand up to darwinian scrutiny at all. I understand that though it is ultra-conserved, whole chunks can be deleted without destroying the resultant organism. bFast
To all: As the discussion is not very lively, I will offer, just as an aside, a new example of informational jump. Histone deacetylase 4 (HDAC4), a very important protein involved in epigenetic regulation. 1084 aminoacids. You already know the game. A second part (on the right of the molecule, C terminal) is occupied by a well known domain, including zinc binding sites. The first part, about 630 AAs, is less defined, although it includes a small domain and an interacting region. As expected, the domain part is well conserved almost everywhere, with some "gradual" increase of similarity to the human form: about 600 constant bits, from insects to lancelet, 750 - 800 bits in fishes, up to about 900 bits in birds and mammals (excluding primates). In a sense, it behaves like the "red" part of Prickle 1: jumps of about 100 - 150 bits. The first part, as expected, presents much bigger "jumps": the homology is rather low and constant in pre-vertebrates, 100 - 200 bits, with 160 in lancelet and a maximum value of 211 in hemichordates. Then we have 800 bits in sharks, and a range of 530 - 830 bits in bony fishes. Big jump. Then, again, smaller jumps: about 950 bits in birds, about 1050 bits in mammals (excluding primates). So: Second part (domain): Pre-vertebrates: 600 bits Sharks: 800 bits Birds: 900 bits Mammals: 900 bits First part: Pre-vertebrates: 100 - 200 bits Sharks: 800 bits Birds: 950 bits Mammals: 1050 bits In a sense, we have jumps everywhere, but can you see where the really big jump is? Again, at the appearance of vertebrates. My point: information jumps are not an exception: they are the rule, and big information jumps are rather common, too. They are not the result of targeted extinctions, as our neo darwinist friends are so ready to believe: they are markers of important functional differences. gpuccio
I would like to discuss here an interesting detail which I have not included in the OP to avoid making it more complex than it already is. My statement that the blue sequence of Hymenoptera is restricted to Hymenoptera is essentially correct, except for a minor exception. Indeed, there is a small part of that sequence which is also restricted, but to a more general group of insects. When I blasted the blue sequence of Apis mellifera against all organisms, the results were confined to Hymenoptera, but a few weaker hits (60 -80 bits) could be found in other insects. Those weaker hits were essentially due, for the most part, to a very short sub-sequence, about 26 consecutive aminoacids in the final part of the sequence, which are very much conserved not only in Hymenoptera, but also in beetles, flies, butterflies and some other insect species, always as a part of the longer "blue sequence". Here they are: LPPRRAYGGVRISYVPNDAVACARKR If you blast these 26 aminoacids, you get isoforms of the prickle protein in insects. Nothing else. So, we could consider this "short motif" (which, however, does not correspond to any known categorized domain) as a functional module which is in some way more widespread than the longer sequences of which it is a part. These observations suggest a very complex modular structure in these accessory sequences. They also confirm a point which I have often tried to make: that traces of functional sequences, even of very short ones like this 26 AAs motif restricted to the Pickle protein in insects, leave traces in the proteome and are easily detected. Sequences are very unique, and their history can be read in the available data, if we look at them with attention. gpuccio
Mung: My idea is that the blue sequences are different personalizations of the Prickle 1 protein in different species, and that they are designed sequences which are coupled to the pre-existing, and more stable, domain part to implement different different regulatory functions in different contexts. When they appear, they are in a sense de novo sequences, engineered in some of the possible ways: from unrelated sequences, from non coding sequences, that could be clarified by future studies and understanding of those mechanisms. Like all de novo sequences, they have no detectable ancestor before their appearance. The interesting thing is also that they remain confined to some evolutionary territory. And that, for the same protein, which apparently should have the same function, there are so many different variations in the accessory sequence, and that those variation are so compartmentalized. The whole scenario seems to be one of modular design, extremely complex and flexible. Of course, I don't believe for a moment that such a scenario can be explained by random variation and natural selection. gpuccio
hi gpuccio, So if I understand you correctly, you do accept that the blue sequences share a common ancestor but that their current configuration could not have been brought about by random mutation and natural selection/drift. Is that about right? Mung
drc466: Wow! A lot of questions. I will try to answer as well as I can. :) 1) It is calculated by comparing the sequences at genomic level. I have taken the nucleotide sequences (from mRNA sequences), and aligned them. In this particular case, I have aligned only the part of the sequences which corresponded to what I have called the "blue" part of the protein. I have then analyzed the alignment by a specific software (the R package seqinr), which counts the number of synonymous and non synonymous mutations, and relates them to the number of synonymous and non synonymous sites. The ratio between the two values is then computed. Here is a Wikipedia page on the subject: https://en.wikipedia.org/wiki/Ka/Ks_ratio The point is, mutations can change the meaning of a codon or not, because of the redundancy of the genetic code. Synonymous mutations, being neutral, should not be influenced by selection. So, they are in a sense a measure of the natural mutation rate between the sequences we are examining. Now, let's imagine that our sequences are pseudogenes, completely non functional. In that case, non synonymous mutations will be neutral too, because there is no function which can be the object of some form of selection. Therefore, in principle, the Ka/Ks ratio should be approximately 1. 2) I am not sure I understand your question. The absolute number of synonymous mutation, obviously, increases with time. So, two sequences which are separated by a long time split will accumulate more synonymous mutations. The point is, if non synonymous mutations are neutral too (see our previous example), they will accumulate too, and the ratio will remain approximately 1. Instead, if non synonymous mutations are somewhat limited by purifying selection, their number will be lower, especially as times passes, and the ratio will be lower than 1. Like in the case analyzed in the OP. 3) I suppose it is, but we should be rather certain of the time span from the split. In many cases, there are big differences in evaluations of the split times between species. 4) I don't understand well this point. Of course, we can use sequences as a source to make "molecular clock" evaluations, but the results are not always precise. Moreover, mutation rates can vary very much between species, in different parts of the genome, and so on. The advantage of the Ka/Ks ratio is that it is a ratio, and so in a way it is independent from all those considerations, and just tries to measure how much a sequence is subject to purifying selection (or maybe to positive selection, but as I have said those cases are more rare). Of course, common descent is assumed in all these reasonings. If you don't accept molecular common descent, you cannot accept any of these reasonings. But in that case, you will have to try to explain what we observe in some other way. Of course we use modern genetic code, but the information in it is not modern at all. When we see an almost complete conservation of histone H3 sequence in all eukaryotes, for example, we can be reasonably certain that we are looking at a sequence which originated a lot of time ago. In a sense, it's like looking at distant stars: the light you see is modern, in the sense that it reaches our eyes now, but what we see happened a lot of time ago. gpuccio
gpuccio, Forgive my ignorance, but a few questions: 1) How is Ka and Ks calculated? Are they equal to the empirical (measured) breadth of mutations across the species? Do these numbers come from publicly available materials? 2) Even if we assume that Ks is a measure of synonymous mutation that does NOT affect amino acid generation, wouldn't there be a cumulative effect? Over time, wouldn't you see Ka/Ks grow as the breadth of mutation increases, and the # of Ks mutations reaches a neutral affect limit? 3) Is it possible to measure dKa/dt and/or dKs/dt? 4) As long as Ka/Ks > 0, and dKa/dt is not vanishingly small, wouldn't that put an upper time limit of how long modern Prickle1 has been "conserved"? Can we backward calculate to a "Prickle1-Eve" in Hymenoptera? Or are you assuming all of these mutations are conserved, and are merely a reshuffling of existing never-changing mutations from generation to generation? I realize I'm beating a dead horse here from two previous posts of yours - but I'm having trouble rationalizing the use of modern genetic code to explicate prehistoric genetic code and common descent and conservation. Could you clear up the four questions above for me? With the goal of answering the question "given the current rate of mutation, how old can Prickle1 in hymenoptera honestly be?" Doesn't the concept of genetic load matter? drc466
Dioniso: Thank you, my friend. Your support is always appreciated! :) gpuccio
gpuccio Glad to see this new OP, after the interesting discussion that followed your previous OP @ https://uncommondesc.wpengine.com/intelligent-design/homologies-differences-and-information-jumps/ Caro Dottore, definitely you're on a roll. :) Mile grazie! Dionisio
Mung: In my view of things, it is not true that "not conserved means no common ancestor". My idea of common descent, as you probably know, is of guided common descent, where some intelligent designer introduces at specific times new functional information, for example in the form of new genes. A designed new gene, or sequence, will not show any homology with what existed before, if the design is rather sudden, and not a refinement of a previous form. However, the whole process of design can happen, and IMO does happens, in the biological continuity of existing organisms: a conscious biological engineering of biological descent. gpuccio
Anaxagoras: Thank you for your comments. I very much agree with what you say. I have not read Denton's book, but I will try to read it as soon as possible. I am absolutely convinced that only conscious and purposeful intelligence can explain complex functional information: it is a "miracle" that no other fact in reality can ever explain. I don't know what Denton means by "naturalistic self-organizing novel principles termed “laws of form”", but I don't think that any credible concept may correspond to that. It seems one of those pseudo concepts of what I call "neo-neo-darwinism", some form of "New Age methodological naturalism", if you allow the term! :) However, I am sure that Denton's analysis may be very interesting, even if I may differ on the conclusions. gpuccio
Hi gpuccio. Doesn't the fact that these blue sequences exist across disparate taxa argue for common descent regardless of sequence similarity? What I am asking is how strong is the inference that because the blue sequences are not conserved it must mean that they did not share a common ancestral sequence? I understand the argument for conserved == functional but saying not conserved means no common ancestor seems to be a different claim altogether. Mung
Gpuccio vs Denton I have followed with great interest these two posts on homologs by gpuccio, while at the same time reading Denton´s new book. Both addresses the same “fact”: the existence of taxa-defining homologs that are specific to groups of organisms. Both consider (although more clearly expressed in Denton´s book) that the specified complexity and funtionality of the traits, at morphological or molecular level, makes implausible that they were formed by gradual functional transitional steps in an unguided evolutionary process. Denton concludes that naturalistic self-organizing novel principles termed “laws of form” might have been at work and that the origin of these homologs was determined primarily by internal causal factors, ultimately derived from the basic properties of bio matter. Gpuccio concludes simply that these homologs represent a solid ground for an inference to an intelligent cause: “Design” Clearly, the cause of this different approach can be found in Denton´s commitment to a strong version of methodological naturalism. Personally I consider Gpuccio´s conclusion much more reasonable and convincing. Order (in the metaphysical sense of classical philosophy) always comes from an intelligent cause. Form is always prior to matter. Fine tuning is not a cause but just a condition for something to come about. Self organization, when talking of the emergence of non previously existent entities is a perfect oxymoron, no contingent being can be its own cause. Anaxagoras
Mung: Welcome! Blue sequences are different in different groups, so they can only argue for local common descent in that group. In all senses, they are a partial counterpart of a de novo gene. Sequences which are conserved from older progenitors, like the red sequence, argue for larger common descent. As we have about 2000 superfamilies, for which no common ancestry can be inferred, we could say that at present we have not any argument for universal molecular common descent. However, as LUCA already showed a lot of those superfamilies, we have some molecular argument for common descent of organisms from LUCA. gpuccio
Hi gpuccio, And thanks again! Doesn't the existence of the blue sequence argue for common ancestry for the blue sequence? Mung

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