Genetic Redundancy and Natural Selection

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.

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.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. 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.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'?As an aside this data once again nicely demonstrates that protein similarity is distinct from genetic similarity since the chimpanzee has the lowest protein identity score compared to the human protein of any of the mammals studied, lower even than the chicken's score, but the chimpanzee's DNA identity score is still the highest. 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.Percy made several other important suggestions for how such redundancy might come about even allowing that all non-synonymous mutations might be lethals.TTFN,WK

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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.

Can you show that the SRC system has always been irreducibly complex? If not, you really don't have a case.Herman Muller figured out IC almost 100 years ago.

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Most present day animals are the result of a long process of evolution, in which at least thousands of mutations must have taken place. Each new mutant in turn must have derived its survival value from the effect which it produced upon the "reaction system" that had been brought into being by the many previously formed factors in cooperation; thus a complicated machine was gradually built up whose effective working was dependent upon the interlocking action of very numerous elementary parts or factors, and many of the characters are factors which, when new, where originally merely an asset finally become necessary because other necessary characters and factors had subsequently become changed so as to be dependent on the former. It must result, in consequence, that a dropping out of, or even a slight change in any one of these parts is very likely to disturb fatally the whole machinery; ... --"Genetic Variablity, Twin Hybrids and Constant Hybrids, in a Case of Balanced Lethal Factors", by Hermann J Muller, in Genetics, Vol 3, No 5, Sept 1918, pp 422-499.
scanned copy

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That is how IC is built. A duplicate gene starts out as an asset, and through mutation and natural selection it becomes a necessity.

No. Try reading through what Percy wrote again. (Or, possibly, for the very first time.)On the cellular level, we do not see:(a) Massive complexes of laboratories to design organisms on a world-wide scale about 6000 years ago.(b) Significant infrastructure for world travel about 6000 years ago.(c) A major genetic bottleneck affecting all species about 6000 years ago.--- (1) You were asked for positive evidence of design, not just an argument of the form "evolution couldn't do that, therefore it was designed". But this false dichotomy is exactly what creationists' blunders over irreducible complexity amount to.(2) You said in your OP: Hence, the system is not irreducibly complex.(3) If it was, then since we know that IC can evolve, it would not constitute evidence against evolution, let alone evidence for design.Edited by Dr Adequate, : No reason given.

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.

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

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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?(I'm not sure, btw, whether Toby and Spring's idea is widely accepted or not. Although the suggestion of animal polyploidy is one I've encountered elsewhere)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.Edited by Mr Jack, : Noticed mis-cite

The idea that there have been multiple instances of whole genome duplication in the vertebrate lineage is widely accepted. Specific examples are the many species of Xenopus, which show ploidy as high as dodecaploid, and the teleost fishes of which the Zebrafish is the most common model organism.There are numerous examples of genes with only 1 or 2 family members in Drosophila which have multiple family members in the vertebrates.TTFN,WK

Sorry, I should have been clearer. Gibson and Spring argue that has been polyploidy a the root of the entire vertebrate line; it's that I'm not sure whether is widely accepted or not.

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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).

Fortunately that model is incorrect.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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Religious belief does not constitute scientific evidence, nor does it convey scientific knowledge.

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?AbE: what Coyote said ^ about pernicious.Edited by Coragyps, : No reason given.

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"The wretched world lies now under the tyranny of foolishness; things are believed by Christians of such absurdity as no one ever could aforetime induce the heathen to believe." - Agobard of Lyons, ca. 830 AD

Which says that it would be difficult for evolution to remove the redundancy, not to create it.

At last, a testable prediction!We see no such thing. Bye-bye YEC model, it was nice knowing you. Oh, wait, it wasn't.Edited by Adminnemooseus, : See the Suspension message triggered by this message

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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.