The Nature of Mutations

I'm posting this is response to Crash, because trying to respond to specific posts by PhospholipidGen and Paul would be redundant and a little late. So here's my contribution to the thread, so far.Crash:I think you may be in a no-win argument here. Both Phospho and Paul have stated plainly that what they require for the ToE to be true is instantaneous (one generation) transmutation (Paul's term) before they will accept the possibility of evolution. Since outside of relatively rare cases in plants this is impossible, nothing that you present is going to be effective. In essence, they have erected an impregnable barrier based on a strawman argument which allows them to ignore all contrary evidence - no matter how many journal articles are presented. As I see Phospho's and Paul's stance, it boils down to (and hopefully they will correct me if I've mistated something):1. Evolution can only occur in individuals, because only individuals reproduce. This of course eliminates in one go all of evolutionary ecology, ecological genetics, population genetics, etc. The stance allows them to ignore population and metapopulation dynamics and the ecological basis of speciation. For example, they are free to ignore hybrid zones between divergent geographic populations, ring species such as Ensatina, the genetic basis for polinator preference observed in Mimulus, the observed genetics of bird speciation, etc etc. Any speciation you present based on the observations that have accumulated over the last 150 years can be safely ignored, because as Phospho has asserted: Obviously, pop gen scientists would disagree - but you'll never get such an admission from either of your two interlocutors. However, if you have access to a decent library, you personally might find the following articles interesting:Orr, A 1995, "The Population Genetics of Speciation: The Evolution
of Hybrid Incompatibilities", Genetics 139:1805-1813Via, S 2002, "The Ecological Genetics of Speciation", American Naturalist (supplement) 159:S1-S7Jiggens, CD and Mallet, J 2000, "Bimodal Hybrid Zones and Speciation", Tree 15:250-255And last but not least, the seminal paper on a 30-year study of speciation by Grant, PR and Grant, BR 1997, "Genetics and the origin of bird species", PNAS 94:7768-7775Of course, since there's no such thing as populations, feel free to ignore them. You might also take a look at the on-line articles I posted earlier for Salty which discuss incipient speciation and Mammuthus's cichlid references. Just remember, it's all variation within a kind. 300,000 species of Coleoptera are all still beetles. On the one hand, we have an extraordinarily broad definition of what constitues "species", and on the other we have an immutable barrier where a significant morphological change is "required" on the order of a chicken-from-a-lizard's egg. As Paul puts it, the demand is:2. Mutation doesn't cause variation within the non-existent populations. Mutation is always negative or neutral. There can be no beneficial mutations (and hence no speciation) without a corresponding and confounding deleterious mutation. Of course, this begs the question of what happens when there ARE positive mutations, such as outlined in numerous articles like:Zhang, J and Rosenberg, HF 2002, "Complementary advantageous substitutions in the evolution of an antiviral RNase of higher primates", PNAS 99:5486—5491

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An improved understanding of the evolution of gene function at the molecular level may provide significant insights into the origin of biological novelty and adaptation. With the approach of ancestral protein reconstruction, we here address the question of how a dramatically enhanced ribonucleolytic activity and the related antiviral activity evolved in a recently duplicated ribonuclease (eosinophil-derived neurotoxin) gene of higher primates. We show that the mother gene of the duplicated genes had already possessed a weak antiviral activity before duplication. After duplication, substitutions at two interacting sites (Arg-643Ser and Thr-1323Arg) resulted in a 13-fold enhancement of the ribonucleolytic activity of eosinophil-derived neurotoxin. These substitutions are also necessary for the potent antiviral activity, with contributions from additional amino acid changes at interacting sites. Our observation that a change in eosinophil-derived neurotoxin function occurs only when both interacting sites are altered indicates the importance of complementary substitutions in protein evolution. Thus, neutral substitutions are not simply ‘‘noises’’ in protein evolution, as many have thought. They may play constructive roles by setting the intramolecular microenvironment for further complementary advantageous substitutions, which can lead to improved or altered function. Overall, our study illustrates the power of the ‘‘paleomolecular biochemistry’’ approach in delineating the complex interplays of amino acid substitutions in evolution and in identifying the molecular basis of biological innovation.

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The article is not only interesting from the standpoint of a non-existent beneficial mutation, but also shows that so-called "neutral mutations" may have a beneficial effect depending on the environment.All mutations are deleterious to the organism. As Phospho notes: "If this is true, please explain how such genetic diseases that are caused by mutations have to do with their environment. Such diseases as Huntington's Disease, or Tay-Sach's Disease, or how about Parkinson's Disease?" {"This" in the above refers to your "The utility (or lack of same) of ANY mutation is due to environment."} Phospho apparently wants to preclude the existence of any beneficial mutation by pointing out that some genetic diseases caused by mutation are deleterious - and by extension ALL mutations are deleterious. Of course, no one has ever said all mutations are beneficial, either. These are certainly deleterious, and it's highly likely that the diseases noted were only able to be fixed in the population (there's that word again) because the environment has changed to make them LESS deleterious by providing medical support, etc. Of course, they have to be homozygous at multiple loci for the full blown disease to show up - and in the case of Parkinsons' most of the really bad things happen well into late maturity (so post-reproductive in most cases anyway).I will agree with Phospho that SCA does have both a negative and positive effect. The action of stabilizing selection is what has allowed the trait to persist. Only heterozygotes get the benefit without the real negatives caused by the mutation, although even here there is some anemia - outweighed by the higher selective effect of not having it at all. Homozygotes with the full-blown anemia tend not to live to reproductive age, and homozygotes without the trait tend to produce less offspring in malaria-endemic areas. So in this case, there is a strong environmental effect that keeps the obviously negative allele in the population. It is a beneficial effect in the presence of Plasmodium, it is negative (either mildly or fatally) in the absence of the parasite.Closing with an extraordinarily revealing quote from Phospho:The funny thing is - artificial selection by humans HAS produced "purple pigeons" - or at least their equivalent. Contrast the amazing differences in pigeon breeds like fantail, owl, trumpeter, jacobin, etc. Basically, pidgeon breeders have created some of the most amazing and bizarre forms you can imagine - something on the order of 2000 recognized breeds. And since artificial selection is being used to develop specific forms pleasing or required by humans, it is directed evolution, not natural selection whose only requirement is that the organism be "well-enough" adapted to its environment to survive long enough to reproduce. As for the "two sets of wings" routine, I'm not sure that is possible. It would require a huge skeletal, muscular, etc re-design. Oh, wait, I forgot, that's precisely what Paul and Phospho demand that evolution produce. Since it doesn't (and quite likely can't), it must be false. My mistake.

I'm afraid you're incorrect. If you'd care to peruse the Zhang & Rosenberg abstract I posted on the previous page? Quite clearly shows substitution - mutation - followed by duplication producing a positive effect (13-fold increase in enzyme activity). You also might find this collection of abstracts interesting: Examples of Beneficial Mutations in Humans. So, after reading those, do you still maintain all beneficial genetic changes are simply recombinations?

Hmm. In a sense, I suppose. However, technically there are two ways variation appears in an organism/population: 1) mutation and 2) recombination during meiosis. They really are two distinct mechanisms. Recombination is NOT a mutation - it's simply the randomization of existing DNA when the chromosomes split and shuffle during normal sexual reproduction (gametogenesis). I'm not totally clear what Phospho is referring to, but when I used the terms it was in that sense.

Or even simpler: Mutation is a failure of the DNA repair mechanism that creates a change in nucleotide sequence. Since mutation can occur in both somatic and germline cells (although, for evolution, only germline are considered), the inheritance requirement in your definition may be misleading. This also allows you to skip neatly over the "are endogenous retroviral insertions mutations?", as well as the "recombination is a mutation" quibble.Quetzal the Semantics Policeman

Arrgh. So much for trying to come up with a simple definition. Is there any way to capture the idea of "mutation" without referencing inheritance (which was really my only quibble with the original posted by crash)? And do so in a way that makes sense in the context of the OP?Welcome back, O Hairy One. We've missed you... (Q has to go back to being careful about what he writes again. *sigh*)

Okay, I've mulled it over some more. I think this is a valid criticism of what I was trying to do, actually. I fell into something of the same trap I did by decoupling natural selection from evolution in those interminable discussions with Syamasu. I'll go along with any base pair difference between parent and offspring, excluding somatic changes, being an effective definition of mutation.However, doesn't this lead to calling genetic shuffling during sexual reproduction (not recombination during meiosis I of gametogenesis) - the other main source of variation in a population between generations - a "mutation"?Quetzal the Stubbornly Confused

All right, now who's being overly reductionist? I don't agree, even for the purposes of this discussion, that we should limit the definition to point mutations. A lot of the really neat evolutionarily-significant mutations that have been identified are more complex. For instance, the drosophila sperm dynein intermediate chain (Sdic) is a gene that was "born" out of the tandem duplication, subsequent fusion, and then deletion of intervening sequences between two original genes.* Not to mention chimerae like jingwei and sphinx. So point mutation only is right out...I was casting about in desperation for some decent definitions that covered all the bases but was also simple enough to be workable. I stumbled across one that seems to fit the bill with slight modifications (from the Physical and Theoretical Chemistry Laboratory, Oxford University). I think this covers Fedhman's inheritance, my structural mutations, and your epigenetic factors, without begging the sexual recombination question. What do you think?*Reference (PubMed citation):

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Nature 1998 Dec 10;396(6711):572-5

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Selective sweep of a newly evolved sperm-specific gene in Drosophila.

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Nurminsky DI, Nurminskaya MV, De Aguiar D, Hartl DL.

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The pattern of genetic variation across the genome of Drosophila melanogaster is consistent with the occurrence of frequent 'selective sweeps', in which new favourable mutations become incorporated into the species so quickly that linked alleles can 'hitchhike' and also become fixed. Because of the hitchhiking of linked genes, it is generally difficult to identify the target of any putative selective sweep. Here, however, we identify a new gene in D. melanogaster that codes for a sperm-specific axonemal dynein subunit. The gene has a new testes-specific promoter derived from a protein-coding region in a gene encoding the cell-adhesion protein annexin X (AnnX), and it contains a new protein-coding exon derived from an intron in a gene encoding a cytoplasmic dynein intermediate chain (Cdic). The new transcription unit, designated Sdic (for sperm-specific dynein intermediate chain), has been duplicated about tenfold in a tandem array. Consistent with the selective sweep of this gene, the level of genetic polymorphism near Sdic is unusually low. The discovery of this gene supports other results that point to the rapid molecular evolution of male reproductive functions.

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Hmm, I may be trying to force too much into that definition, but I think the "chemical rearrangement ... in a chromosome" covers structural mutation while leaving normal recombination and random shuffling during fertilization as "non-mutation". Feel free to make it more clear by changing the wording. After all, the objective is to come up with a definition that covers the wide range of possible mutations while at the same time restricting things to something that the creationist can't weasel out of...

I'm afraid you did. Or at least that was what the following sentence seems to imply. Would you care to rephrase it to explain what you really meant, if this was not your intent?

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Yes, this is what I am saying, to the best of my knowledge. All supposed "mutations" that are considered purely beneficial are in fact not mutations at all, but simply genetic changes such as recombination. But recombination is not a mutation. (emphasis added)

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Please clarify.

Your attention invited to the reference provided in my post #90 of this thread. In addition, in an earlier post I referenced an article by Zhang and Rosenberg which also referenced this question. I will quote the abstract here:

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An improved understanding of the evolution of gene function at the molecular level may provide significant insights into the origin of biological novelty and adaptation. With the approach of ancestral protein reconstruction, we here address the question of how a dramatically enhanced ribonucleolytic activity and the related antiviral activity evolved in a recently duplicated ribonuclease (eosinophil-derived neurotoxin) gene of higher primates. We show that the mother gene of the duplicated genes had already possessed a weak antiviral activity before duplication. After duplication, substitutions at two interacting sites (Arg-643Ser and Thr-1323Arg) resulted in a 13-fold enhancement of the ribonucleolytic activity of eosinophil-derived neurotoxin. These substitutions are also necessary for the potent antiviral activity, with contributions from additional amino acid changes at interacting sites. Our observation that a change in eosinophil-derived neurotoxin function occurs only when both interacting sites are altered indicates the importance of complementary substitutions in protein evolution.Thus, neutral substitutions are not simply ‘‘noises’’ in protein evolution, as many have thought. They may play constructive roles by setting the intramolecular microenvironment for further complementary advantageous substitutions, which can lead to improved or altered function. Overall, our study illustrates the power of the ‘‘paleomolecular biochemistry’’ approach in delineating the complex interplays of amino acid substitutions in evolution and in identifying the molecular basis of biological innovation.

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As to variation arising from mutation within a population, there are innumerable studies where this has been documented. One of my favorite examples is Orr HA, 1995, "The Population Genetics of Speciation: The Evolution of Hybrid Incompatibilities", Genetics 139 180.5-1813

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Speciation often results from the accumulation of complementary genes, i e . , from genes that, while having no deleterious effect within species, cause inviability or sterility when brought together with genes from another species. Here I model speciation as the accumulation of genic incompatibilities between
diverging populations. Several results are obtained. First, and most important, the number of genic incompatibilities between taxa increases much faster than linearly with time. In particular, the probability of speciation increases at least as fast as the square of the time since separation between two taxa. Second, as Muller realized, all hybrid incompatibilities must initially be asymmetric. Third, at loci that have diverged between taxa, evolutionarily derived alleles cause hybrid problems far more often than ancestral alleles. Last, it is easier to evolve complex hybrid incompatibilities requiring the simultaneous action of three or more loci than to evolve simple incompatibilities between pairs of genes. These results have several important implications for genetic analyses of speciation.

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That'll do for you to go on. Your turn. You have stated numerous times that your assertions have been "demonstrated" (such as in this quote: To date, you have failed to provide any references in support of any of your assertions. Please do so.[This message has been edited by Quetzal, 05-03-2003]

This is the best you can do? I provided (over the course of several posts) four references specifically refuting various assertions of yours. All you are capable of is picking one out-of-context, off-the-cuff remark from a post that wasn't even addressed to you? For someone who makes the remark: you have made a very poor showing. After all, you have been given substantive rebuttals to your assertions, but are completely unwilling to even acknowledge them. Whether or not you are more than the average creationist, your tactics to date have been quintissentially typical, run-of-the-mill creationist: to wit, unable to counter or even discuss the evidence brought forward counter to your position, you fall back on insult and denigration followed by a change of subject or a re-assertion of your original point. This is NOT the attitude of someone who is not "playing games".Would you care to try again, or are you merely bluffing?

Hi Phospho. Glad you decided to stick around. I suggest you re-read the abstract of that article. The authors make no assumptions whatsoever (in the article, anyway) about whether evolution has occurred or not. Here, let me quote the relevant portion for you again - the bit right after the sentence you disagreed with since it contained the word "evolution".

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We show that the mother gene of the duplicated genes had already possessed a weak antiviral activity before duplication. After duplication, substitutions at two interacting sites (Arg-643Ser and Thr-1323Arg) resulted in a 13-fold enhancement of the ribonucleolytic activity of eosinophil-derived neurotoxin. These substitutions are also necessary for the potent antiviral activity, with contributions from additional amino acid changes at interacting sites. Our observation that a change in eosinophil-derived neurotoxin function occurs only when both interacting sites are altered indicates the importance of complementary substitutions...

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Please note here that they are making an observation that they have discovered a "parent" gene that has a limited function, and which due to duplication and subsequent mutation, a "new" gene was formed that has a significant increase in functionality. I posted this reference not in the sense of showing evidence for evolution per se, but rather as a pretty obvious counter to your assertion that mutation cannot cause "beneficial" change. Here is an example - quite well documented - wherein a mutation enhanced the function of the pre-existing gene, without destroying its functionality.What I find interesting in your reply, especially in light of subsequent discussion on this thread (especially with Crashfrog), is that you quite specifically ignored the second reference I provided in that post (Orr 1995). In that article, Orr discusses how mutation can cause the development of allelic incompatibility in the hybrid zones of a graduated cline. IOW, he describes the genetic basis for reproductive isolation between two conjoined populations of a single species. Since it has been quite well-documented that reproductive isolation is the key to speciation, observing that genetic incompatibility is arising in the "mixing zone" between two populations of the same species is a significant indicator that the two populations are being viewed "at the instant of speciation".Since by your subsequent definitions "speciation" cannot occur, I think Orr provides an interesting counter.

I think you may have this backwards. Variation both between individuals and between populations of a given species was observed. The observation was made that two species of a given type of animal were much more similar the more close together they were geographically. The observation was made that utterly unrelated species could have similar morphology if they inhabited the same habitat type on opposite sides of the world. Finally, there were discoveries of the bones of long dead animals that were not related to - although possibly similar or suggestive of - any living organism. The theory of evolution was derived to explain these observations. The observations were not "adopted" - they formed the basis for the theory. That's a rather odd definition of speciation. You seem to be claiming that the only true speciation results in completely novel lifeforms. IOW, that "species" represents some kind of discrete entity - a class of objects with definable boundaries and specific properties - rather than a designation for an amorphous group of closely related organisms. The line separating species A from species B is often pretty arbitrary - and sometimes it doesn't even make sense. For instance, the leopard frog (Rana pipiens) has a range that extends from southern Florida to northern Minnesota. It's classified as a single species from one end of its range to the other. However, the physiology and behavior (one clutch per year in Minnesota, 3-4 clutches per year in Florida) of the northern populations (cold adaptation, hybernation, 1 clutch per year) is really vastly different from that of the southernmost populations (warm adaptation, year-round activity, 3-4 clutches). The extremes should really be considered different species, IMO - but what do I know? I'm not a taxonomist. However, be that as it may, I hope you are beginning to see why your demand inre speciation is unrealistic - it's simply not what's observed nor is it what evolutionary theory expects/requires. Interesting. Now your asking US to document something that shows the opposite of something only you claim exists? You'll need to provide the specific citation (or at least the source) for Mayr - I've read a fair amount of his work, and this doesn't ring any bells. As an alternative, please document the alleged barrier that supposedly separates taxa. I think I addressed the first part of this above. Evolution says nothing about "one species giving rise to another" if by this you mean saltation (frog giving birth to a turtle, for instance). You might be interested to know that Darwin didn't say anything about speciation - his book was about natural selection, adaptation, and descent with modification - in spite of the title.Beyond that, you've been given a fair amount of both the specifics AND the generalities of evolutionary theory. Could you please clarify exactly what it is that you want/expect, here? The generality is the applicability of evolutionary theory to biodiversity. The specifics are going to be case-dependent, but are all going to fit within that framework. I'm not clear on what the problem is. You're free to pick either/or or both.Modern evolutionists "cling to change" (as opposed to what, exactly, stasis? immutable "kinds"?), because that's what evolution is all about! The change from ancestral to the modern forms. You can look at it from the short-term (relatively speaking) perspective, in which case you are talking speciation, population dynamics, etc. Or you can talk about change in the long term covering the vastness of geological time (phylogenetic evolution). It's only when you try and blip back and forth between the two perspectives that you start getting into trouble... Again, you're going to need to provide a more complete reference on this claim. Where exactly did Mayr deviate from science? What specifically did he say? Context is everything in these discussions... This almost sounds like you're advocating reinventing the wheel. After all, the data - the raw observations - are out there, documented, and available. All you'd need to do really is take all of the observations that had been made - the brute facts, if you will - over the last 150 years or so, and come up with a new theory that tied them all together. If it could be shown that the new idea was a better one that the ToE - that it explained the facts and observations better - then I'd be among the first to pitch it. Maybe you could spend some time and do that. In the meantime, however, I think I'll stick with the idea that explains the majority of the data, thanks all the same.

I think this might be a very interesting conversation to continue on the "emergence of species" thread. I posted a reply to Ned and Percy at this post.I didn't do it this time, moose. [This message has been edited by Quetzal, 06-02-2003]