Adding information to the genome.

This seems like a totally baseless assertion. Most point mutations are neutral, but even those that aren't are rarely null mutations. If you mean that they affect the pattern of gene expression rather than actually rendering the gene inoperable then you are using a concept of information which totally decouples it from the processes which actually produce functional biological variation.You seem to be saying that there are mutations which can cause phenotypic variation which can be acted upon by natural selection but which do not constitute changes in information. This makes whatever measure of information you are using essentially irrelevant to the concept of evolution. Heritable variation with a phenotypic effect causing a difference in reproductive success, at whatever level that variation is generated. Of course this need not only apply to conserved features since this description equally well encompasses deleterious mutations.TTFN,WKEdited by Wounded King, : No reason given.

I think it is the simultaneity of the mutations that RAZD is questioning rather than the multiplicity. He is positing multiple sequential mutation spread out over geological ages. What is your evidence? As RAZD says there are numerous fossil examples of intermediary forms of jaw/ear bones, are you saying that these are all examples of rare surviving examples of disadvantaged sports which just happened to be fossilised? There is considerable reason to doubt such a claim.TTFN,WK

No, it wasn't. It was more like 20 years ago. Since the 80's researchers have been finding many different types of conserved non-coding genetic elements. It is hardly surprising that now that sequnceing is so much cheaper and easier more and more of these things are coming to light. Now if you were talking about coding for proteins then 2% would probably still be the answer you would get.You seem to be taking genetics to task for not knowing things that there were absolutley no readily available genetic methods for discovering at the time. Ohno's original 'junk' DNA paper was published in 1972, 3 years before the first reliable sequencing method was developed by Sanger. Wow, you really don't know what you are talking about. They were teaching about regulatory pathways when I was in University 15 years ago and it was already well established developmental genetics by then.TTFN,WK

No it doesn't. How does a double knockout of Dlx5 and 6 suggest that loss-of-function mutations are what are responsible? If you think that what the double-knockout produces resembles an ancestral phenotype then you are arguing for a chain of gain-of-function mutations. If not then where do the genes whose function was lost exist? Have they been expunged from the genetic record when they lost their function? Should we expect to see them in animals with jaw structures considered more ancestral? I agree with you here, I just think that what has 'built in' the compenstory elements is the duplicative evolutionary origin of the Dlx network, neither the DLx5 or Dlx6 knockout has as severe a phenotype as the double mutant. indeed the single mutant knockouts show a great deal of reduncdancy with them both regulating similar sets of downstream gene required for mandibular development in branchial arch 1.I would also point out that while null mutants, the naturally occuring equivalent of a knockout mouse, can be the result of single mutations they are one of the more radical levels, and certainly a study across species and phyla using phylogenetics does not show a pattern of progressive gene loss in most cases. Rather what we see are generally small scale nucleotide level changes, a few larger effect indels and some rare but very large effect chromosomal genomic level mutations. What you seem to want to ignore is that small single nucleotide level changes can also have widespread developmental effects which need not be detrimental in the way that the double knockouts, and indeed pretty much all the single knockouts were, i.e. causing the mice to die before or soon after birth. Except there is no evidence for such pre-existing information. It is well worth noting that morphological convergence is a very distinct thing from genetic convergence. A marsupial and a placental may appear to share a gross morphology but genetic analysis will tend to show that the placental more closely resembles other placentals genetically. Similarly some elements of the development of the independent middle ear are thought to have arisen more than once, but there is no evidence that the same mutations gave rise to them.I'm also not clear how such 'activation' is consistent with your previous loss-of-function characterisation of the process. Do you see activation as the result of the removal of repressive genes or driven by front-loaded mutation causing a new gene/function to be expressed. These would seem to predict different patterns in the guided genetic evolution of the DNA. Or do you think it may be an inconsistent mixture of multiple different mechanisms?TTFN,WKEdited by Wounded King, : No reason given.

I'd say that quite a few other modifications would be required for the modern state but clearly modifications of Dlx5 and
Dlx6, or their downstream targets have been important.Another thing I'd suggest is that these modifications need not be in the actual coding regions of the genes themselves but rather in the regulatory regions which determine where the genes will be expressed. There is a familial case where loss of an enhancer element common to Dlx5 and Dlx6 led to a failure of the inner ear to develop properly (Brown et al., 2009).From what you've said in this post I'd just like to welcome you to the evolutionary side in this debate TTFN,WK

Not so much really, but I understand you believe that. All that is nothing but empty assertion. The idea that 'subordinate' genes only have one regulator, or only 1 type of regulator, is nonsensical. There are multiple families of transcription factors, of which the homeobox genes are only 1 superfamily comprising multiple different families of transcription factors including the Hox genes and the Distalless-like family (Dlx). Homeobox genes are found in very primitive organisms indeed, such as sponges and cnidaria but even before these genes arose there is no reason to think many of the genes downstream of them in modern networks weren't already extant and regulated some other way.We had a previous poster on this site who thought he had a killing blow against evolution with research showing that a coral had homologues to genes which were found to be expressed in the developing human nervous system. He chose to ignore the fact that the same genes were also involved in early morphogenic movements around gastrulation and found in species throughout the animal kingdom, instead he trumpeted the result as [thread=-1756], and went on to claim the genes were 'genetic sequences for complex nerve function'. For my response to his argument see my Message 263The problem with saying things like "It's another chicken-and-the-egg conundrum" is that you ignore the fact that evolution gives us a clear and obvious answer for that, eggs predate chickens, and indeed birds in general, by millions of years. Similarly comparative developmental and genetic studies show us the sort of primitive developmental networks which can be ramified through duplication and variation to the more complex developmental networks we see in modern metazoans.Your "Simultaneous and mutually-dependent cause and effect" simply isn't needed because the various components of these networks are arising, multiplying and developing dynamically in line with the increasing body plan diversity we can see in the fossil record.TTFN,WK

Here is the core of the problem right here. You started with a statment which does refelect what Kimura says and which I doubt Percy or anyone would object to, after all if selective pressures become very acute then stasis in a viable form may be the only possible survival strategy. Then you go on to make a statement that is an outright caricature of Kimura, where he says 'selective contraints' you substitute the ridiculous 'erroneous tenets'. But he should also explain why he doesn't find your argument effective, not merely restate his own.TTFN,WK

you are making a whole series of unwarranted assumptions about how such genes should arise or act, with the possible exception of point 1. The fact is that as long as there are protein domains which can promote expression either by recruiting transcriptional machinery directly or by opening up the chromosomal structure to allow transcription, then these domains can be joined to almost any one of dozens of DNA binding domains whose specificities can be highly variable. This allows a decoupling of repressing and activating activity as a domain for either can be associated with a similar binding domain.We can see this capability in in vivo experiments when a fusion of the Engrailed-repressor protein domain to a binding domain of some other transcription factor acts to repress the direct transcriptional targets of the transcription factor, no matter what its normal activity would be. The converse experiment uses the VP16 protein domain which is from a Herpesvirus and is a potent transcriptional activator. For an example of such experiments see Li an McGinnis (1999) where they use the VP-16 domain to change the regulatory activity of specific Hox genes in Drosophila and study how they alter segment identity.TTFN,WK

I think that except for discussions of systems of 'evolvability' you will find this to be the case for almost all evolutionary biologists. The creation of variation is by various mutational processes, and it is generally the case that these variations are considered to arise in a stochastic manner essentially insensitive to any selective pressures the organism may be experiencing. This is one reason why even if mutations are not truly random, in terms of being equiprobable, in their distribution through the genome they remain random in terms of their effects on the fitness of the organism.It is this random mutation that is the very basis of virtually all genetic variability. The difference between Kimura's neutral evolution and adaptive evolution is simply in the way that the patterns of genetic variability are captured from one generation to the next. In neutral evolution the patterns are influenced by stochastic effects and random sampling, in adaptive evolution benefifical alleles/mutations tend to increase in frequency due to improved reproductive success of the organisms carrying them. These processes are not mutually exclusive, non-adaptive variation can be carried to fixation on the back of a nearby beneficial mutation and even the strongest beneficial mutation with a huge selective advantage may be extinguished from the gene pool by some random factor.You seem to be arguing against a straw man version of evolution where natural selection is the source of variation as well as the mechanism/force which acts to maintain adaptive variation. Kimura's focus is on Random mutation/ Random selection, the 'Darwinian' model's on Random mutation/ non-random selection. They may argue the exact extent to which particular regions of the genome are ascribable to either factor, but they believe in the same source of variation.Surely what Kimura's theories are truly antithetical to is a belief that the genome was purposefully created? If junk DNA is all really functional and we just don't appreciate it, which a number of ID proponents suggest, then why does it look like the product of mere randomness?TTFN,WK

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAARGH!!!How can you still not understand something no matter how many people tell it to you in how many ways. Variation is no more the result of drift than it is of natural selection! Variation is a result of mutation. Some of the patterns of variation we see in the diverse genomes of organisms are best explained by neutral drift, others are better explained by selection. Also please stop appealing to Kimura, it seems pretty clear by now that your understanding of what he says is tenuous at best. Why not just give us your own thoughts on neutral theory? We probably all actually agree with Kimura, the person we don't agree with is you. This is in fact the crux of the matter, and the constraint that Kimura objected to, this sort of hyper-adaptationist view that every evolved feature should be adaptive. It is also a view of evolution that virtually no evolutionary biologist holds anymore, certainly not in terms of molecular evolution. And now you are back to the same totally unsupported claim you were making in the first post! You are again using 'information' in a completely vague and useless way. Why can changes below the level of a whole de novo gene not consitute increases in information? Or are you allowing modification to encompass increases in information, because if you are then you seem to have no argument at all. Again, this is disingenuous to the point of dishonesty. It is selection that allows the construction of the specified complexity by maintaining functional variation. It is the initial variation that is generated by random forces.Why can you only talk about one part of the adaptive evolutionary process at a time? You only seem to be able to think of random mutation or natural selection in mutually exclusive terms. Why can't you understand that it is principally the interaction of the two that leads to the adaptive evolution of the specified and complex functional sequences we see today?TTFN,WK

Why not instead try and employ some reading comprehension? There is a vast amount of newly generated genetic variation in the available genomes of living populations, and even more represented in the sperms and ova of those populations, that will never be passed on to subsequent generations. The source of all this genetic variation is mutation.What we see when we compare genomes is variations that have occurred at vastly different points in those genomes' evolution. Some will have occurred just when this embryo was conceived some it will have inherited from ancestors millenia ago.There is a major difference between the source of variation and the reason for the particular patterns of variation that we see. Your continuing to conflate them will not change this.I'll expand a bit on what I meant in my previous post by random selection, it is essentially the same as genetic drift. Random selection is any factor which changes the proportions of alleles passed onto the next generation which is not influenced by those alleles.An example - we breed 2 mice. These are diploid sexual organisms so their offspring will have roughly a 50 % contribution of genetic material from each parent. Exactly which copy of each parental gene they inherit is the result of random events during meiosis. Similarly exactly which sperm meets which egg is effectively random. Therefore the offspring of this mating will have a set of genomes which does not replicate the allelic proportions of their parents. If we keep breeding the pair for many more litters the proportions should become closer and closer to the parental ones. We could do the same for a whole population of mice, and randomly reassign mates for each new litter.The converse situation would be if instead we used some selective criteria for the matings. Suppose we only bred the top 10% of mice in terms of running speed. clearly the subsequent generation would have an allelic distribution radiacally skewed from what we see in the random mating scenario. There will be some genes, totally unrelated to running speed, for which this will essentially still seem random, so even while strong selection is being applied to one trait others may still be effectively evolving through drift.There are any number of factors which can affect the reproductive success of organisms in a population completely independent of that organisms genetic makeup or phenotype, and all of these factors can contribute to genetic drift.TTFN,WK

Indeed, in fact that was exactly the point I was making that you thought was contradictory. The other point is that using this interpretation natural selection is also one of the processes resulting in variation we see since it also 'decides' what variation remains.To take your poker analogy further lets say you just keep your original hand while I keep my best cards but draw the rest again, doesn't being able to keep good cards and be able to redraw increase my chances of having a good hand? And doesn't it, more importantly to our discussion, also affect the 'variation' of the hands we have at the end of the game?The ongoing discussion in evolutionary circles is how much of the variation we see in the genome is determined by which process, drift or natural selection. No-one, other than you apparently, believes that only one of them is in operation. That is why Kimura says that the fate is largely rather than solely determined by drift.Indeed most bioinformatic approaches to finding 'information' in the genome consist of identifying sequences, or specific nucleotides, whose patterns of variation have been reduced by selection.TTFN,WK

I'm really beginning to doubt there is any point continuing this dialogue.You just keep on reiterating the same stupid assertions, fail to acknowledge the many substantial rebuttals and then proceed to talk more nonsense about what biologists believe. These aren't junk DNA, your entire argument seems to be based on wilfully misunderstanding almost any piece of biology you encounter. Pseudogenes, the nonfunctional remnants of duplicated genes, are definitely considered junk DNA for the most part but still functional duplicates certainly aren't. Being subject to a "relaxation of selection" is not the same as being junk DNA. That is a claim so vague that it might well be true, but it is an astronomical leap from 'severely constrained' to effectively impossible to arive at naturally. Yes, but that is in variation as a whole, if you actually look at elements with functional variation then that role shoots up. No it doesn't, and no matter how much you put your fingers in your ears and go 'LA LA LA' you aren't going to change the fact. If you really think Kimura says that then you are incapable of reading properly.TTFN,WKEdited by Wounded King, : No reason given.

Percy is somewhat more than a moderator. He pretty much runs the whole kit and caboodle, down to writing the software the site operates on.TTFN,WK

Your quotes in no way address anything I said, for the reasons Percy and others have already highlighted. When any novel mutation arises de novo it is of course at very low frequency in the population. The statistical reality is that almost all such low frequency alleles will be removed by drift. In fact there is a good case to be made that drift acts as much to reduce variation within a population as it does to maintain it.Go to any genetic dfit simulation and you can see this, take http://www.biology.arizona.edu/...ution/act/drift/frame.html as an example. Plug in a population size, up to 10, and a number of generations to follow and you will see that the majority of the variation in the population is in fact extinguished by the operation of drift.One issue with that simulation is that the effects of drift are exacerbated due to the very small population sizes allowed. For a simulation allowing you to study larger populations,albeit for only one allele, go to http://darwin.eeb.uconn.edu/simulations/jdk1.0/drift.html . If you set the p value to 0.1, a low frequency allele, then you can see that the alleles frequently run to extinction, until you get to higher population sizes. What natural selection does is to affect these trends by giving beneficial alleles a better chance of propagating (or rather the traits we consider to be 'selected' are the ones that do this themselves). Go to http://darwin.eeb.uconn.edu/simulations/selection-drift.html to see the effect of selection on the previous drift simulation. Even with a much smaller starting frequency the alleles can reach fixation in a much shorter space of time than by drift alone. This doesn't avoid the operation of drift however, in a small population even strongly selected alleles still often run to extinction. The problem is that you refuse to understand or stick to what Kimura says. You keep trying to graft on your own misunderstandings and try and piggy back them through using Kimura's authority.TTFN,WK