Summations Only

Others are dealing with some of the basic issues you have brought up so I thought I might look in more detail with a specific case, the Melanic Moths.Since the last time this topic was discussed here on EvC a couple of new papers have been published, both from the same lab.The first, (van't Hof and Saccheri, 2010) took what is known as a 'candidate gene' approach, looking at genes known to be associated with melanisation biosynthesis in other insects. They looked at 16 'candidates' and found that none of them were associated with the locus linked to melanism in Biston betularia.I would suggest that the very fact that there are several different gene candidates associated with melanism would argue against the sort of front loading scenario you suggested. Surely if there was a pre-existing adaptive program in insect we would expect it to target the same gene, if no tproduce the exact same mutation, in the various instances of melanism that we have studied?The second paper follows on by going through further genetic crossing to refine the localisation of the region linked to the carbonaria phenotype (van't Hof et al., 2011). In this paper they manage to narrow the region down to a 200kb stretch, still quite large, which is associated with wing patterning. This paper raises another issue with the call for some sort of definitive proof for the origin of a novel feature. When they arise in closely associated populations in which there is reduced or no reproductive isolation then there is a possibility for introgression to reintroduce genetic variation into the wild type population making it very hard to distinguish this introgression from existing low frequency standing variation.I find it hard to believe that whatever the genetic basis within that 200KB stretch that it will be something impossible to produce from known mutational mechanisms. That said it is hard to see how outwith catching such a feature arising under laboratory conditions the exact nature of the actual causative mutation can be known, we are really limited to making informed inferences from known mechanisms in the most part, but if such mechanisms are sufficient I don't really see the need for any sort of special pleading.TTFN,WKP.S. What you call gene plasticity is normally called phenotypic plasticity .

OK, so that wasn't me, it was Taq. That aside your point is obscure, are you claiming that these were always existing alleles rather than novel? That the only difference is in expression changes?If the first then it is largely a moot point, the paper identifies 4 amino acid substitution mutations (not start codon disruption as you claim) in Mc1r, all of which are single nucleotide substitutions. The authors don't definitively identify which one or more mutation is the actual cause of the melanic phenotype in the Pinacate mice but it is hard to see what argument you could make that would bar such an allele arising at random through known mutational mechanisms although I suppose a probability case could be raised if 3 or 4 of the substitutions are required.The paper also notes that there is an entirely different basis for melanism in the Pinacate mice than in the similarly phenotyped melanic Armendaris mice. They also note that these specific Mc1r mutations are distinct from ones that have previously been associated with melanism in other melanic mice, again a point arguing against any form of programmed adaptation.I'm still confused as to what you meant when you describe the mutation as 'a start codon disruption', the only thing I can think is that you were getting mixed up by the description of the black-and-tan mutant mouse ... But even then the mutation clearly isn't described as a start codon disruption, it is a disruption of the promoter sequence roughly 15kb away from the start codon. You don't seem to have understood this paper very well. What you seem to be saying is that creationists will admit the existence of beneficial mutations provided they are allowed to hold an unfounded belief that these mutations were the product of intelligent design. Where is the evidence for such genomic programming? I think this characterisation needs to be clearer. Are you saying that the mere existence of the immune system anticipates the existence of the phenomenon of infection in general or are you making the much more controversial claim that the immune system anticipates specific antigen challenges?If it is the second then this just highlights one isssue with the IDist creationist approach, ignoring selection and the generative power of random mutation. The generation of immune variation through VDJ recombination is well understood and it is not based on any sort of specific anticipation of a challenge but rather on building up a vast repertoire of immune variation such that almost any immune challenge will have a suitable epitope that is targeted by some antibody. The generation of this vast immune repertoire is principally driven by the recombination of of the V(D)J elements, addition of random untemplated nucleotides in complementarity determining regions and through subsequent somatic mutations in the immune cells. These mechanisms allow the generation of sufficient diversity to recognise more than 10⁷ different epitopes. The system also produces many broken recombinations, including some frame shifts which effectively destroy the MHC protein, and long stretches of untemplated nucleotide which are effectively non-functional, many of these non-functional forms are strongly selected against in the bone marrow so what is seen circulating in the body is already a population selected for a minimal level of functionality.This is not anticipation in any meaningful sense. Yes they have, they just haven't provided substantive evidence to support the claim. No one disputes the existence of deleterious mutations, but to claim that all deleterious mutations are random and all beneficial ones the result of 'programming' requires some really substantial evidence to support it because at the moment all the evidence suggests they are both generated through exactly the same molecular mechanisms. Contrary to what evidence? There is good evidence that small genetic changes in one or 2 genes can produce hybrid inviability and
sterility or postzygotic reproductive isolation, key elements of speciation under the BSC (Presgraves et al., 2003;Mallet, 2006). That isn't to say that we can identify specific causative mutations that led to speciation, because it turns out there can be hundreds of such hybrid incompatibility genes between species and it is challenging to impossible to determine which one would be the initial isolating mutation, especially since these may have arisen subsequent to reproductive isolation through some entirely different mechanism such as geographical isolation of the parent and daughter populations.The genetic evidence for small mutations giving rise to reproductive isolation is clear. Where is your evidence that such mutations can't contribute to speciation?TTFN,WKEdited by Wounded King, : spelling

Actually this is incorrect, the achondroplasia (or chondrodysplasia) in dogs is caused by an additional copy of FGF4 rather than a mutation in FGFR3 (Parker et al., 2009). The authors do however speculate that the effect of this additional copy may be to indirectly cause misexpression of FGFR3.In regard to the current discussion they make this observation ... Intriguingly they looked for a particular combination of genetic characteristics, an FGF4 gene with a particular rare haplotype that the retrogene copy has and the 24Kb haplotype that characterises the site where the retrogene inserted. They didn't find that combination in any modern dog breed that they looked at but did find it in wolves from Europe and the middle east.They also raise they key issue when looking at domestic dog breeds in the context of evolutionarily novel features ... TTFN,WK

What do you think genetic drift is? You seem to be using it here in a context that makes very little sense. Genetic drift is a phenomenon like selection that acts on already existing variation, it does not generate novel variation itself. The question is what makes this a 'detrimental' mutation? If it provides a selective advantage to the organism is it still a 'detrimental' mutation? Now here the answer could be genetic drift, at least that and a fair helping of selection. Of course in the case of domestic dogs the answer is almost certainly artificial selection, humans chose to systematically breed dogs with the trait with other dogs with the trait until the trait became fixed within the breed. The basis of speciation is a separate question from the origin of novel features. If you want to talk about speciation you should probably start a thread on that topic. If we are discussing the de novo origin of a feature we are rarely going to be discussing speciation since we are interested in how the trait arises within a population.TTFN,WK

Oh dear, we seem to be running into the creationists not knowing what they are talking about phase of this thread very early. What you seem to be trying to describe has nothing to do with the mutations identified in the melanic Pinacate mouse. I assume that by the rather word salady "DNA ORF’s frame shifting" you are trying to say what they saw was a frame shift mutation, it wasn't. None of the mutations they describe are frame shifts. If you are talking about frame shifts in relation to this paper then you are just making things up. If you aren't talking about frame shifts then I have no idea what it is you are trying to talk about. As others have said, the modification of existing alleles is considered one on the major sources of novel functionality, either in the genes original form or in a duplicated copy. This seems like a remarkably arrogant statement given the tenuous understanding of the paper you have presented so far. Because if there exist preprogrammed alleles, whatever that means, for specific traits then it seems reasonable to expect the same traits in related species to be associated with the same genetic/allelic basis. Given the multiple different genetic bases for melanic phenotypes in mice this seems to suggest that there is no such preprogrammed allele. You could say any nonsense that crossed your mind, why should anyone care? You seem to be using 'fluid' and 'fluidity' to mean that whatever turns out to be the case will be consistent with your hypothesis. Still word salad, words don't mean whatever you want them to mean. A frame shift is when an insertion or deletion of one or more nucleotides disrupts the open reading frame (ORF) of a gene and subsequently changes the reading of the codons downstream of the mutation site. You could consider a mutation which destroyed the start codon to be a form of frame shift, though technically I would dispute that, but either way none of the mutations mentioned in the paper are either of those things, they are neither frame shifts nor disruptions of the start codon. Ah, finally, something to indicate what you actually mean, unfortunately you seem to still be very confused. The ORF is not shifted away from the start codon, for that to happen there would need to be an insertion directly after the start codon. What happened in the black-and-tan mouse is that a distant promoter sequence was disrupted. The one correct element you hit on, there had to be one sometime, is that the effect is associated with a change in regulation. This is an important point because changes in the regulation of expression of genes can be just as important as changes in coding sequence in terms of novel traits. For a good example of this just consider the already mentioned short legged dog phenotype which arose from a duplication of FGF4 leading to a different pattern of expression given the different genetic context the copy was inserted into. Well it is hard for me to understand what you mean because it bears little to no resemblance to how molecular genetics actually works. You seem to have just picked up a whole lot of technical terms without going to the effort of actually understanding what they mean and think that stringing a few together will take the place of a coherent argument. As to why the paper seems so complicated for you to understand, I would be hard put to say, but I think it might be that you just don't have a very good basic understanding of molecular biology and genetics. Dammit Zaius! I gave you the choice of 2 options and your answer is yes? Seriously?!Is it ...A) The mere existence of the immune system anticipates the existence of the phenomenon of infection in general.or ..B) The immune system anticipates specific antigen challenges. I agree, discussing whether the immune system is IC is a topic for another thread, though it is a claim that has already been substantively rebutted. Eh? Do you mean that the excerpt is an example of what you object to? Because it doesn't lay out any objection, it just summarises their finding that they identified a specific molecular basis for hybrid inviability between two species.As to your pathlight reference, this is a frequent and bizarre creationist straw man that almost all drosophila experiments involving mutation have been with the intention to produce a new species, someone should really inform the biologists who were doing the experiments, they will be very surprised.You seem to be, rather unsurprisingly, using the term speciation in an idiosyncratic creationist way that has little to nothing to do with how it is understood in biology. You say that but I get the feeling that you really don't, if you did you might actually take the time to read through the paper thoroughly and understand it, as I suggested, rather than making barely coherent arguments with a whole lot of technical terms just thrown together with a few new terms you seem to have made up.TTFN,WKEdited by Wounded King, : spelling

That said, it is still challenging even in prokaryotes. If we look at the ever popular long term evolution experiments in E. coli from Lenski's group we will find a few cases where there is a tie between phenotype and genotype but many more where the linkage is unclear. Even the genetic basis for the much publicised evolution of oxic citrate metabolism is still unclear 4 years later.TTFN,WK

No it doesn't, it just accepts the reality that genomes already exist which be modified. This was not always the case but the totally de novo origin of a coding sequence is not relevant in discussing the melanic mouse. Given the fact that we have several instances of such a phenomenon occurring it can hardly be called magical, see New genes in the Human lineage for a discussion of a paper on this in humans. Except they did specifically identify the gene in one case Mc1r and could clearly exclude the causative region that they found in that case as the basis for the other. If you want to argue with their methodology and show it is flawed then you are going to have to actually make an argument rather than just claiming that they have shown nothing.It is true that they didn't characterise the exact molecular mechanism to the extent of identifying the exact responsible mutation or mutations and how it gave rise to the phenotype. I'm at a loss as to how you think this fact takes away what they did show which was the close asociation of the phenotype specifically with these 4 mutations which were not seen in the other population. I never doubted you read it, merely that you understood it. Once again, "a frame shift by promoter disruption" is a biologically meaningless phrase, it describes no known type of mutation. Please stop using these two phrases together. Is it a frame shift or a promoter disruption. If you want to claim it is both then you need to show how such a mutation would satisfy both characterisations, so far you have not done so. And so we come to another common creationist trope, that any change to the system is essentially degradative. The alternative, clearly, is that changing genes promotes new and unique functions. You say damaging without any clear basis in fact. I'm quite happy to admit that there are many case where a beneficial mutation is the result of the total disruption of a gene which is certainly classifiable as degradation, but there are also man instances where this is not the case. Can you explain in what way you consider the mutations described in the pocket mice paper to be degradative? Interesting if were true, sadly you seem to have misunderstood yet another paper. It may well be that this mutation can be found extant in Grey wolves, but there is no evidence for that in this paper. In fact table S4 in the supplementary materials shows that the insertion never occurred in the wolf specimens they studied.What they found was that the 24Kb haplotype for the site into which the retrogene inserted was found in the wolf and further that the FGF4 gene haplotypes in the wolf were similar to those of the retrogene in the short stature dogs. They did not find a retrogene insertion in the wolf. If you still wish to claim they did please provide some evidence. Well the point is that the scientific research clearly shows something and you consistently misinterpret and misrepresent it to try and say it does not.You can claim pre-programming till the cows come home but sou have yet to provide a scintilla of evidence to support that claim. Maybe you are just talking to someone who has studied molecular biology. I was addressing your specific question of why I found your argument so difficult to understand, and explaining that it was because you use terms from molecular genetics but you don't use them in a coherent fashion, the primary example being your persistent use of 'frame shift' to describe things which simply aren't frame shifts. Oh dear, finally we see the inevitable emergence of the underlying creationist troll from beneath its polite veneer. Should I begin assuming that all your other apparent instances of severe reading incomprehension can also be ascribed to this puckish wit? It would make more sense than assuming you are debating in good faith given your apparent inability to correctly understand a single paper that has been discussed. And? What is your point? There is no problem with this in terms of evolutionary theory. The idea that post-mating reproductive isolation occurs as a byproduct of adaptive evolution on a related trait is commonplace. Seriously? You are questioning common descent between 2 different species of Drosophila? You wouldn't even have to go outside of the creationist 'still just fruit flies' comfort zone to accept this one.I guess that Ark must have been pretty crowded with representatives of every biological species concept species on it. Clearly you aren't an adherent of the post-diluvial rapid speciation scenario. I prefer to think of them as astute observations on your pattern of behaviour so far.TTFN,WK

This is a really bad answer to an admittedly badly constructed question.Natural selection is not a selective pressure itself, it is a term which captures the action of all the varied selective pressures acting upon a population. In the paper the authors suggest that the relevant selective pressure acting on coat colour is predation, principally by owls.Secondly sexual reproduction is hard to class as a molecular mechanism and is also not a very tenable explanation for the origin of these mutations. Are you suggesting that the 4 separate Mc1r mutations that were identified as highly associated with the melanic phenotype were brought together to form this trait due to allelic recombination?The actual molecular mechanism giving rise to these mutations originally was probably any one of a number that cause point mutations, although the fact that 3 of the changes are C->T transitions (see Fig. 3) suggests that deamination could have been an important factor.TTFN,WK

Actually the answer to this is very straight forward, there is considerable interbreeding between the dark and light populations. The second paper to have been referenced mentions this, indeed Zaius himself quoted a relevant extract in his very next post after he posed the question, Message 66, there are "high levels of gene flow between light and melanic populations."Indeed in yet another paper on this topic (Hoekstra et al., 2005) the authors note that "high levels of gene flow between neighboring melanic and light populations suggest the selection acting on color must be quite strong to maintain habitat-specific phenotypic distributions".TTFN,WK

I've been rather halfheartedly drafting a reply to Zauis Message 44 for the past few days, but the discussion seems to have moved on quite a bit in that time and there were some sections relevant to the current direction, and particularly Tangle's question in Message 80, that I thought I would extract and present here.We were discussing peripherally the action of the FGF4 retrogene insertion in short legged dogs and the fact that the genetic makeup necessary for such an insertion was not found in other modern dogs but rather in a grey wolf population. Zaius suggests that this may be a frequently occurring spontaneous mutation in the wolf population, which is merely strongly selected against, and so cannot really be considered novel. That is a perfectly reasonable argument and raises the question of how novel a feature can be considered when it has a low but significant rate of spontaneous appearance in a parent population, even if it is subsequently strongly selected against as in Zaius' example. Should we consider it novel simply if it was absent in the founding population? Taken to an extreme the alternative approach rapidly takes us to a position where our imperfect knowledge of the genetic makeup of previous generations makes it impossible to definitively consider any mutation novel as we can't confidently state that it never occurred transiently in any ancestral population.I'd say that for pragmatic purposes we would have to look at simply the extant variation that we can see and in the case of a line where we actually known the genetic makeup of the founders it is reasonable to consider a genetic feature novel that was not present in that founder population, I say a genetic feature rather than a phenotype since recessive traits could easily be masked for few generations.I think this is relevant of the discussion of the melanic mice because there are several other examples of adaptive colouration in other mouse species where the mutation has gone in the other direction from dark to light ( Hoekstra et al., 2006; Linnen et al., 2009; Steiner et al., 2009).Without a much larger scale phylogeny taking in the relatedness of these several rodent species, it is very hard to say which trait is truly ancestral and which derived and certainly not if the trait is novel in a broader sense. I would say that we can pragmatically determine given a certain depth of genetic information whether a trait is novel to a particular population as I outlined above.The above papers are also interesting as they touch on Zaius' challenge to me to show him some examples of adaptive mutations that weren't 'degradative'. As is often the case this is problematic as Zaius hasn't given us a clear definition of what he considers 'degradative', indeed he has made comments that suggest he might be using the term so broadly that any genetic change will fit it regardless of its effect.So within these various papers we have the initial example of the light to dark mutation set in the pocket mice. The function of the melanocortin receptor is to mediate the signalling from certain hormones which bind to the receptors, this mediation is done via the generation of cyclic-AMP (cAMP), the level of cAMP then determines whether the target cell produces eumelanin (Darker) or phaeomelanin (Lighter). So in terms of the genetic concepts of loss- or gain-of-function the melanic pocket mouse mutations in Mc1r are gain-of-function mutations giving rise to a more sensitive receptor balanced more towards eumelanin production (Nachman, 2005).However when we look at the other papers we see a light phenotype arising both from gain-of-function mutations increasing the expression of the Agouti gene, which inhibits the binding of melanocortin to its receptor, and through loss-of-function mutations where the binding specificity of the receptor for melanocortin is reduced and so is the level of cAMP, tipping the balance towards phaeomelanin production.So we have a very heterogeneous mixture of mutations, albeit all centered on one or two genes, some are gain-of-function mutations, some are loss-of-function, In some populations the derived mutations are those producing the light colouration, in others the dark and in some there are a mixture of derived alleles in both genes giving rise to a spectrum of melanic phenotypes.So given all this messy complexity how do we address Tangle's question, how do you distinguish the new, derived allele from the ancestral one? This usually comes down to being able to compare to another population considered to have common ancestry (which is undoubtedly an unfounded assumption in Zaius opinion). Polymorphisms/mutations which are found to be present in either of your populations of interest and your more distant outgroup are considered to be ancestral and those found in only one population to be derived. Since there is no way to be sure that you have captured the entire genetic diversity of a whole population in these sorts of cases these are always probabilistic inferences.TTFN,WKEdited by Wounded King, : SpellingEdited by Wounded King, : No reason given.

Honestly, I'd quibble with this argument. The synonymous/nonsynonymous ratio tells us more about selection and the timing of the selective pressure rather than the relative temporal origin of the alleles' necessarily. So while it is consistent with a recent origin I'd suggest it is equally consistent with a strong selective pressure bringing an already existent low frequency allele up to near fixation levels. I'd be careful of treating this as some sort of slam dunk for the timing of when the allele first arose.I'd say that the fact that there is a different basis for melanism in the other dark population of the same species is better evidence for the dark alleles being a derived trait than the variation levels. If there was an already existing melanic trait in the species it would be reasonable to expect that it would be the selected melanic form in both populations.TTFN,WK

Sorry for the confusion, I assumed you were talking about synonymous mutations since you specified that the mutations were neutral. I'm not sure what you mean, I'm not suggesting purifying selection is the reason for the lack of variation. The point is that a sudden switch in selective pressure can vastly inflate the proportion of a low frequency allele beneficial in a new environmental context, this expansion will be accompanied by a similar expansion in the representation of the SNPs/haplotype associated with that allele. So the lack of variation can represent a recent expansion rather than a recent origin, for exactly the same pop. gen. reasons.TTFN,WK

Which is almost exactly what Zaius was saying in Message 48.TTFN,WK

There is more than one form of nylon eating bacteria, the first and most commonly cited case is the purported frame shift mutation identified by Susumu Ohno in the 80's (Ohno, 1985) in a strain of Flavobacterium. Ohno makes a convincing argument that the nylon degrading enzyme originated from a frame shift mutation in an already existing open reading frame that coded for a sequence with no apparent enzymatic function. Since the nylon degrading strain was isolated in the wild there was no direct ancestral population to compare it to so there is no concrete evidence that the hypothesised point mutation is what actually occurred. Additionally the fact that the nylon degrading sequences occurred on a plasmid, and is associated with a transposase like sequence IS6100, has been used to argue that the enzymes were imported from some external population or that plasmids are some sort of intelligently designed system for metabolic diversity in bacteria.Similarly functioning enzymes, again associated with a plasmid and sequences similar to IS6100, were identified in Pseudomonas. The sequences for one pair of the enzymes between the species was also very similar with 99% homology (Tsuchiya et al, 1989) which has been taken to suggest that in this case there was horizontal transfer of the enzyme between species.More convincing evidence for a novel origin of nylon digestion comes from in vitro culture experiments were nylon digesting strains have been dervied in the lab. This has been done for Pseudomonas (Prijambada et al., 1995) although no specific molecular basis has beenidentified for the trait. A similar experiment in Flavobacterium only managed to identify a further, previously unrecognised, nylon degrading enzyme on the pOAD2 plasmid.So there is no clear ambiguous novel molecular mutation giving rise to nylon digestion that has actually been well documented. We have a well documented origination in Pseudomonas, from the in vitro experiments, but no molecular basis, and a good candidate for a molecular basis in the case of the nylb gene in Flavobacterium but no clear ancestral population/strain for comparison.TTFN,WK

If that snippet is supposed to support the idea that there was a wild type sequence that Ohno compared then reading the rest of the paper would quickly disabuse you of the notion. Ohno puts in many qualifiers and caveats that make it clear that the 'pre-existed' sequence he mentions is a hypothetical one inferred from the current ORF, for some examples see Message 4.There may have been a wild type gene that was sequenced, but it isn't in this paper and I'm not aware of a paper that it is in.TTFN,WK