Genetic Redundancy and Natural Selection

I hate to start a new thread at a time when I am already vastly behind in my replies on other threads - but I just read an interesting article by Dr. Peter Borger on the topic of genetic redundancy (Dr. Borger is an inactive member of these forums I believe).Dr. Borger's primary assertion is that natural selection and gene duplication can not account for the startling level if genetic redundancy found in the genome.He uses the SRC gene family as an example case. Summarizing his explanation, the SRC genes code the family of proteins (8 in total) that activate cellular division. Non-synonymous point mutations in these genes are often lethal because they code proteins that don't "turn-off" leading to cancerous cell division.SRC proteins are not identical (sharing only 60-80% of their sequences), so since these genes are highly selective against mutation it is highly unlikely that they arose as a result of gene duplication - they would have to have evolved separately.While mutation often results in a lethal phenotype knockout experiments on SRC genes show that mice can survive without some SRC genes.Now, Dr. Borger argues this as evidence of a designed system - and initially I agree with his assessment - but I'd like to give my darwinist friends here the opportunity to provide a rational explanation. How is it possible for evolution to generate redundancy within genetic systems?

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You *are* a bit busy in other threads, but I have a couple requests for this thread proposal.

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Certainly - sorry for not being more clear.

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Could you define "non-synonymous point mutation?" Not everyone is going to know what that means.

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Assuming I don't have a misunderstanding of the concept myself - a non-synonymous point mutation is a change to the nucleotide sequence (GATC) in a gene that causes a corresponding change to the protein(s) coded by that gene by replacing one amino acid in that protein chance with a different one. Because of the redundancy in the genetic code many mutations are synonymous: they change the DNA nucleotide sequence but do not result in a change to the resulting protein because they still code for the same amino acid.

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And could you explain how evidence *against* evolution as an explanation for SRC genes is evidence *for* a designed explanation?

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Design is simply the conclusion that I and the author of the article draw. I could go into detail, but it seems to be beyond the scope of the question. I'm not asking readers to come to the conclusion of design - I am asking readers to demonstrate how darwinian evolution explains genetic redundancy. I ask because I'm curious if a functional hypothesis has been developed yet within the darwinian framework.

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Issues outside the intended scope of your thread proposal are probably best left unmentioned. There's an edit button.

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Good point - here's why I mentioned the conclusion of design: The article I linked is the first in a series. Dr. Borger outlines in subsequent articles a YEC design-oriented baramin-based hypothesis that seems to fit the data rather well. I'm wondering if darwinian evolution has a corresponding hypothesis - and if so how well does that hypothesis fit the data? (I'm not trying to be condescending here - I'd really like to know!)

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Okay, if you could include a link to the message in Biological classification vs 'Kind' where the baramin-based hypothesis's supporting evidence is outlined then that should be fine.

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Sorry...I'm not sure I understand. I don't think I've posted the supporting evidence in the Biological classification vs. 'Kind' thread (unless there is a specific post you are referring to?). It was my intention to bring up some of it in responses to posts on that thread - or are you asking me to post the evidence on that thread and then link it from here? I'm happy to comply - just not sure I'm following what your request is.

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One of the primary goals of EvC Forum is to host discussions that actually get somewhere, and we attempt to achieve that goal through moderation that keeps discussions from drifting off topic or leaving points hanging or unsupported and so forth. We also try to make sure topics are clearly defined before they're promoted.

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A noble goal indeed.

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If you're planning to take your thread in a direction that's based upon baraminology that I'd feel more comfortable if we had a working definition of baraminology and its supporting evidence. So if it's not already in the Biological classification vs 'Kind' thread then that would be a good place to put it.

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I don't intend to discuss baraminology in this thread - I was hoping to receive one or more answers to a specific question posed to darwinists.I agree it would be good to define baraminology and its evidence - and I have been and will continue to try and do so in that thread. My only reasoning for mentioning mine and Dr. Borger's conclusion of design here was so that respondants would understand my perspective on the issue. Since it is possible my bias toward YEC thinking is influencing my conclusion I may not have adequately considered possible evolutionary hypotheses to answer the question I posed. I felt disclosing my position would give those who responded a better frame of reference to answer the question.Does that clear things up? If you still disagree I will happily edit out the mention of my conclusion.

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There really are people named Peter Borger out there. One of them did used to be a post doc fellow at the University of Sydney. And one did used to be at the University of Groningen in the Medical Sciences college where he published a number of papers in the technical journals in the 1990's. And maybe this Peter Borger's real name is actually Peter Borger, but whoever he is, the information about his credentials is unlikely to be correct.

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I don't know Dr. Borger personally - I have no clue about his credentials nor do I really care. Whoever wrote the article in question makes some good points regarding natural selection and genetic redundancy. The point here is not to perform a character assassination on the author of the article. The point is to demonstrate how evolution can account for this problem. I asked a very specific question and am hoping for a very specific answer - neither really has anything to do with Dr. Borger. I wouldn't be surprised if you and others dodge the question and instead attack Dr. Borger's credentials - but that would lead me to suspect that you don't have an answer....However, if it needs clarified Dr. Borger has defended his credentials here on these forums. Now, would you please approve the thread?*Edit: Sorry, after re-reading the above I may have come across rudely - that was not my intent. I appreciate you pointing out the supposed flaw in Dr. Borger's credentials (now resolved), but didn't find it particularly applicable to the question I posed.Edited by BobTHJ, : Added clarifying note

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I tried to verify Borger's claim that single non-synonymous point mutations in SRC genes are fatal, but none of his references mention the SRC gene family, and I also couldn't find anything online. Where's the evidence for this claim?

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Borger gives this quote: And attributes this source: Let me know if anyone has access to this paper. I'm curious what it says.

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But for the sake of discussion let's just assume it is true that single non-synonymous point mutations in SRC genes are fatal. In that case, how could the rest of the members of the gene family have arisen? Some possibilities are:

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Other types of mutations that are not point mutations, of which there are many.
A frame-shift mutation inactivating one of the duplicated genes followed by more mutations followed by another frame-shift mutation that reactivates the gene.
Evolution in an organism whose makeup was not vulnerable to at least some types of non-sysnonymous point mutations in the SRC gene.
I'm sure there are other possibilities, I'm not a biologist. What's important to note is that the possibilities I listed do not posit never-observed processes or mechanisms.

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Thank you, you did present some possibilities. However, consider there are 8 (or 9) genes in this family. So - not only would the gene have to be duplicated the appropriate number of times (a reasonable assumption) but then each of those variants would have to undergo either:
1) A series of non-fatal mutations. Apart from point mutations, these would be what - insertions and deletions? Assuming Dr. Borger's assertion is correct I'm not sure how that would result in a less lethal phenotype.
2) a deactivation, followed by mutations into a different functional protein, followed by a reactivation (improbable).Your third option is a possibility - though without knowing if SRC mutations are lethal in all known organisms it is difficult to know if this is a reasonable option.Let's assume for a moment that one of the methods you posited was sufficient to create the redundancy in the SRC genes. How does redundancy occur across a large portion of the genome. I could see (given adequate time) this event occurring once - but repeatedly hundreds or thousands of times? What mechanism does evolution have to preserve a redundancy? Natural selection works against it.

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If the model for design is the way humans design, then in a YEC scenario we should see evidence of massive complexes of laboratories to design organisms on a world-wide scale about 6000 years ago. There would also have to be significant infrastructure for world travel in order to transport organisms from their point of design/creation to their intended environment. We should also see a major genetic bottleneck affecting all species about 6000 years ago.

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Funny you should mention that - because that is exactly what we see at the cellular level. Intensely complex machinery working in synchronization, operating from a set of coded instructions that code multiple tasks simultaneously, and a self-regulating self-repairing, redundant system to carry it all out. The complexity far exceeds the limits of mechanics or computer science. But the random, imperfect nature of the evolutionary process explains it perfectly, right?

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Can you find evidence for any of this? Can you find any positive evidence for design at all, instead of just negative claims that "evolution couldn't do this, therefore it was designed?"

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You mean, other than the irreducible complexity I eluded to above? Nope that's it. See what you want to see.

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So, if Dr. Borger is correct, God sat down and figured out how to make a gene so that any of the inevitable mutations that could occur in this gene cause cancer in the organism that gene was in?
Because nothing says intelligent design like a big ol' tumour.

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No, no....try and understand the YEC model. Creation was perfect. God created a variety of genomes that had the ability to modify themselves and adapt to a wide variety of situations. Mutation is a product of the fall - of sin entering the world. Now the once perfect genome is deteriorating: losing large chunks of information and mutating to degenerate or fatal phenotypes. If the YEC model is correct we should see more degeneration of the genome (ie a higher rate of disease, cancer, loss of function, declining lifespans etc.) as time progresses. The semi-recent revolution in medicine has staved this off to some extent, but in the end it will succumb to the crumbling genome (unless technology is developed to repair/restore it, which is a possibility).

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This gives 2 wrong impressions, firstly that activating cellular division is all the SRC gene family proteins do, which it isn't, and secondly that they are the only genes that activate cell division which they aren't. If these were true it would greatly strengthen his argument about redundancy, but they aren't true.

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Cell proliferation is only one of the many biological functions the SRC genes are involved in, they also regulate aspects of the immune response, cellular differentiation, motility and adhesion as well as a number of other things.

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Thank you. Out of curiosity, could you provide me a link to a paper detailing some of the other functions of SRC-family genes?

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As Percy says, it is very hard to find anything that actually backs up this statement. Certainly we do know about mutations that produce constitutively active forms of SRC especially, since it has massive historical importance in our understanding of cancer and oncogenes, but to turn that into a blanket statement about many more mutations in all of the SRC family genes extends well beyond where the evidence takes us.

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Agree. Borger does need to provide the data to back this claim.

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A more usable approach than looking at orthologs in one genome would be to look at homologues in different genomes. NCBI have helpfully already calculated the similarities for a whole lot of pairwise comparisons here. If the chimpanzee SRC protein can differ by 40 amino acids why should we imagine that those substitutions are not tolerable in the human form of the protein? What does this say about the genes being 'highly selective against mutation'?

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A darwinian approach would assume the chimp SRC gene to be compatible with humans - an ID approach not so much. Though it would be interesting to know....

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The very same way that Borger dismisses, via gene duplication. As long as one looks at the reality of the biology rather than presupposing that the genes essentially can't tolerate any non-synonymous mutations, then the problem suddenly ceases to exist.

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Winzeler, E.A. et al., Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis, Science 285: 901—906, 1999 shows that gene duplication can not account for even half of the cases of genetic redundancy. Let's step back from the SRC gene and look at the big picture for a minute:The moment a gene is duplicated mutation begins to act upon it, modifying it from its twin. As long as the gene remains functionally redundant to its paralogue then there is no positive selective pressure to maintain that gene (it does not add to the fitness of the organism). Thus natural selection has no method of retaining redundancy. It lasts only for the short (relatively speaking) duration until mutation drives it away from functional redundance. Yet we see a remarkable level of redundance in the genome - far more than can be accounted for by recently duplicated genes.We also see dormant genes that code for functions not normally expressed. These cryptic genes are activated by extreme environmental pressures on the organism. How does natural selection preserve these dormant/cryptic genes when they are not typically expressed and therefore provide no fitness benefit to the organism (except under certain extreme conditions)?

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No. Try reading through what Percy wrote again. (Or, possibly, for the very first time.)

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On the cellular level, we do not see:

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(a) Massive complexes of laboratories to design organisms on a world-wide scale about 6000 years ago.

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(b) Significant infrastructure for world travel about 6000 years ago.

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(c) A major genetic bottleneck affecting all species about 6000 years ago.

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Try reading what I wrote again. Note the words "...at the cellular level."As to the genetic bottleneck, the baranome hypothesis accounts for this. Baranomes are pluripotent. They contain a host of dormant genes to allow the organism to thrive in a wide variety of environments and contain the genetic machinery to induce rapid variation and speciation.

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Hence, the system is not irreducibly complex.

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(3) If it was, then since we know that IC can evolve, it would not constitute evidence against evolution, let alone evidence for design.

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Your logic is flawed. I could see you arguing this line of reasoning if you could demonstrate piece by piece the reversal of a process without the destruction of the functionary (still not sure I'd agree - but at least you'd have a logical argument). However, you are suggesting that since a single piece of a system can be removed and the system will still function then it must not be irreducibly complex - this argument has no merit.

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That "quote" does not appear anywhere in the letter (mis-cited, btw, it's Gibson, T.J. and Spring, J.), the nearest is this:

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However, in the KH and SRC cases, many, perhaps almost all, point mutations that damage the protein product also cause a deleterious phenotype. So the genetic redundancy cannot easily decay away through the accumulation of point mutations.
Being charitable we can forgive the paraphrasing to "in the redundant gene family of SRC-like protein" as perhaps meant as a clarifying alteration, although noting that it's bad form to alter a quotation without pointing out where you've altered it.

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The section "and kill the organism" however is simply not found anywhere in the letter.

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If this is a case of mis-quoting (and it appears it is) then Borger should have been more careful to notate his modification to the quote.

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Most astonishing however, in it's dishonesty, is Borger's following line:

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If the SRC genes are really so potently harmful that point mutations induce cancer, how could this extended gene family come into existence through gene duplication and diversify through mutations in the first place?
This is dishonest (or incompetent) in two ways, firstly he ignores a key part of the quoted line "many, perhaps almost all point mutations that damage the protein". I draw your attention to how that is a distinct subgroup both of point mutation, and of non-synonymous point mutations. Borger is dishonestly (or incompetently) acting as though this is not the case. Secondly, and more damningly, the question he poses is answered in the source he cites. The whole thrust of Gibson and Spring's argument is that the redundant gene family arose not by gene duplication but by polyploidy! So why does Borger not address this point?

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It is doubtful Borger is trying to mislead. Based on the context it is clear Borger is speaking about non-synonymous mutations. And what makes you think that Gibson, T.J. and Spring, J are referring to a subset of non-synonymous mutations? All non-synonymous mutations "damage" the protein (though in many cases for non-SRC genes this still results in a valid phenotype). Maybe I'm wrong though - I can't read the article myself so perhaps they specify this more clearly.I'm not sure why you think Borger should address a polyploidy origin. It seems a pretty weak hypothesis considering the SRC genes are located at different spots on different chromosomes. Again, I don't have access to the cited article - so maybe they explain this?

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Also, for interested readers, I found a discussion in which Borger was thrashing out the ideas he later formed into this article, I haven't look in depth at it yet: it's here if anyone wants to trawl through it.

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Thanks - I'm reading through it and finding it interesting. I'm a bit disappointed by Borger's arrogant and wild claims at the start - but it seems he shapes up a bit once you get a little further into the conversation.Edited by BobTHJ, : a bunch of typographical goofs

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Fortunately that model is incorrect.

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Because you said so it must be true?

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And incidentally I regard the notion that humans are inherently flawed and evil as the most pernicious notion that has ever been concocted in a shaman's diseased mind.

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I'm sorry you disagree. I find the notion that humans are wise and good enough to divorce themselves from their Creator to be arrogant, unhealthy, and foolish.

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So fast-replicating critters like houseflies and Staphlococcus that also tend to get the short end of the stick on most health-care plans are at the brink of extinction now, ridden with cancer and ever-shorter lifespans? I hadn't noticed that trend, Bob - do you have any documentation of it?

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I'm not sure how you got from my statement regarding a degenerating genome to this. Care to explain? What does fast replication have to do with my statement?And no - I don't have evidence - but I'm sure somewhere someone is keeping statistics on this stuff. This is a prediction for the baranome hypothesis - and it can likely be proven true or false to some degree of accuracy within the next 50 years or so (though environmental agents such as carcinogens as well as medical efforts to prevent disease do rather complicate the recordkeeping).