Does the Darwinian theory require modification or replacement?

I think the immune system is probably a good example of where people's objections to Shapiro's use of non-random comes in. The immune system does not presciently produce antibodies tailored to a specific future challenge nor does it produce them initially in response to such a challenge. Instead a huge number of random, though constrained and not equiprobable, antibody variations are produced. When one of these encounters an antigen to which they correspond then they can stimulate an expansion of and further mutation in the particular subpopulation of antibody producing cells corresponding to that antibody. But this production of high affinity antibodies again works by producing a vast repertoire of randomly mutated, though constrained and not equiprobable, variants and relies on subsequent selection to pick the highest affinity ones.I think this links to a point Slevesque raised previously about foresight. What we see in these systems is not the result of foresight but feedback. Not all outcomes are equiprobable some mutational systems have a constrained spectrum of mutations they can produce, many transposable elements have specific affinities for target sequences they will insert into, certain chromatin states are genetic sequences are more susceptible to mutation than others.All of these mean that mutation is not truly random but none of them provide any mechanism of foresight or even genuinely directed mutation. At best some of the feedback mechanisms skew the probabilities slightly so certain classes of mutation become more likely.TTFN,WKEdited by Wounded King, : SpellingEdited by Wounded King, : No reason given.

Shadow, you have to get out of this revisionist genetic history of yours. Mayr's book may have been published in 2001 but the position he was discounting was one that hadn't been current for decades.In the same 1972 paper in which Susumi Ohno coined the term 'Junk DNA' he was proposing reasons why the non-coding proportions provided a selective advantage. As it happens his proposals were fairly conservative and mostly to do with structural features of the genome. Without considerably more refined technology it is hard to see how he could have anticipated the extent of function of non-coding RNAs, he was after all writing this before, or concurrent with, the development of the earliest DNA and RNA sequencing techniques.And as I pointed out previously in our discussion of Mattick's work functional roles for non-coding RNAs have been put forward since the 80's and actively researched since the 90's.In fact it seems to me quite remarkable that within 30 years of those earliest sequencing technologies having been developed, when sequencing 24 base pairs was an achievement, we had the publication of the first draft Human Genome sequences in 2001.TTFN,WK

Really? Doesn't that make this whole thread rather pointless then since the current evolutionary synthesis is already a substantially revised form of Darwinian theory and incorporates these discoveries? The only thing that will tell us where these will lead in the future is time. Any evidence to support this? I'm sure they didn't think they were wrong, and indeed they weren't. But I see no reason to believe that they considered what they outlined mathematically to be the be all and end all of evolutionary research. No he didn't, that was still me. Sadly your approach seems to tend strongly towards the leading and to be very light on the evidence.You seem much happier throwing quotes from Mayr, Mattick and Shapiro at us than actually presenting any evidence to support the claims you are deriving from what they say. What should anybody care exactly what Shapiro himself means by non-random if the evidence does not support the interpretation of it you are using?TTFN,WK

That is an interesting little article, a nice summary of some or the misleading mathematical approaches which we see occasionally in arguments for ID or creationism.However It doesn't really seem on topic for this particular discussion. Maybe it would be better going into the Links forum.TTFN,WK

Well how about instead of just saying it you actually cite some research showing the mechanism that produces non-random beneficial mutations? Rather than simply mechanisms that slightly affect mutation rates, or that insert in specific but highly frequent sites in the genome, or that insert very common transposable elements. Show us some evidence in fact that these things are 'directed' in any meaningful way rather than simply being environmentally induced stress responses that may turn up a few beneficial variants but are just as likely to produce deleterious ones. Because all deleterious means is that the mutations impair the organisms survival/reproductive success. So you might make a case that the tendency of natural selection is directed by the organisms environment, but that is just standard Darwinism. If you want to argue against Darwinism because selection isn't random then you have misunderstood things badly.Variation is produced by a 'random', in the subjective rather than the frequency interpretation of random, spectrum of mutations. These mutations are then 'selected' by the organisms environment with those promoting survival and reproductive success tending to increase in frequency and those detrimental tending to decrease.Talking about selection says absolutely nothing about the nature of the mutation that gave rise to the trait or the frequency distribution of beneficial and deleterious mutations arising. But it isn't, it is quotes from people you consider the appropriate experts. You aren't citing their work, just parroting their soundbites. We discussed the basis of the mutations Shapiro considers 'non-random' and told you why most evolutionary biologists/ molecular geneticists would not agree with that description. So you simply saying, yet again, 'well Shapiro says they are non-random' adds nothing to the discussion. The fact that you think that just emphasises the fact that you are approaching this as a lawyer rather than a scientist. Actual scientific evidence showing a bias towards beneficial mutations, especially specific ones, in experimental populations would be evidence, what you are providing is simply opinion.TTFN,WKEdited by Wounded King, : No reason given.

Thanks for clearing that point up, you do have no idea what you are talking about.TTFN,WK

I already addressed that paper in the previous thread Message 958. I'll copy my reply here. If this is your directed mutation then it is the weakest of weak sauce.TTFN,WK

When you are talking about bacteria then pretty much everything is lamarckian since there is only a single cell involved. A mutation in the main chromosomal DNA of the cell will have as much effect as a mutation during mitosis wuld on the daughter cell.In a very real sense the majority of bacterial evolution is Lamarckian. It is only with the establishment of a germline/soma distinction that offspring stop inheriting virtually all the mutations that their parent organisms acquired.TTFN,WK

Hey Jar,The thing is there is actually very little in the way of evidence that these mechanisms operate in most sexual organisms, certainly in most metazoa.We can certainly see the effects of transposable elements in mammalian genomes, for instance, and the inherent mutational biases and hotspots are apparent. But there is no equivalent stress response which would affect the mutational spectrum of germline cells.The closest thing is perhaps the effect that heat shock can have in some organisms, Fly (Rutherford and Lindquist, 1998) and C. elegans are the model most work has been done on, which can reveal previously hidden conditional mutations. But in this case the stress response is revealing the mutations to natural selection, by removing normally present stabilising elements, rather than modifying the mutation rate.TTFN,WKEdited by Wounded King, : No reason given.

Not necessarily, it is just that there is no evidence for such mechanisms operating in metazoa, and such mechanisms would need a radically different operation in large multicellular organisms compared to unicellular ones.If we look at Wright's mechanism for instance it rapidly becomes clear that in an organisms with a sequestered germline you aren't going to see the same interaction of genome to environment in terms of de-repression of genes in response to a challenge. Consequently the bias for mutations in transcriptionally active sites will not be towards metabolic genes triggered by the response.Instead we might expect to see a pattern of bias towards genes transcriptionally active in germline development and early embryonic development. Such genes would be likely to affect survival of the particular cell lineage in which a mutation arose and, arising early, such a lineage would be likely to have a chance of contributing substantially to the germline.TTFN,WK

Neither really, what I meant was that mutations occurring at such early embryonic stages, say pre-gastrulation for example, have a good chance of contributing significantly to the germline cells.Also since those early embryonic stages can be quite sensitive to mutation there would be strong negative selection against deleterious mutants occurring at that stage.So if transcriptionally active/derepressed genes are more liable to mutation then at these early stages that bias would be towards genes associated with early development which are prime candidates for being subject to strong selective pressures due to the sensitivity of early development.TTFN,WK

I've heard it both ways I admit I was exclusively focusing on the 'inheritance of acquired characteristics' aspect.TTFN,WK

Well the idea from Wright's article is that the bias towards derepressed/transcriptionally active genes focuses mutation, good and bad, on those genes. Over the entire population this may lead to a higher proportion of beneficial mutations suitable to the current stress. In this new speculation we might say that it will tend to make early development more robust.TTFN,WK

Yeees ... but, the main point is that the mutations occur around that point as well, otherwise we aren't looking at a situation analogous to Wright's. As Dr. A reminded me a key distinction here is that the mutation is a response to the environmental challenge, in this case the environmental stresses an embryo is subject to at early stages. Unless we have this bias towards genes involved with that specific stage and maintaining it in the face of environmental factors then all we would have is the normal mutation/selection cycle.My point in emphasising the early embryonic stages is that subsequently, once the germ/soma division has been established, almost all the transcriptional responses to environmental challenges will be limited to somatic cells, and consequently any resulting mutations will be solely somatic. There is indeed evidence for the rates of somatic mutation being related to transcriptional activity, so that element of the hypothesis is at least consistent. Without some way to feed information back from the soma to the germline, which there is no evidence for, such responses are irrelevant to the discussion. That is why the only feasible stages are very early embryonic ones, or possibly genes involved in germline maturation and gamete production.In fact it would be interesting to look and see whether there is any bias in the mutational spectrum in sperm towards genes involved in sperm production. Of course wright specifically ties the mechanism into de-repression not just transcriptional activity, so that would narrow the relevant pool of genes even further.TTFN,WK

No because, as my subsequent post pointed out, I was making it up as I went along. I was trying to devise some hypothetical mechanism that would work in metazoa, specifically mammals, equivalent to the one Wright was describing in bacteria.So since these were my own hypothetical mutations I could make them non-random, to the extent that their transcriptional state made them more likely targets for mutation. As for their beneficial or deleterious state, as Jar suggests it could go either way. Wright's argument was that by increasing the proportion of mutations in genes involved in a particular response you were more likely to generate relevant beneficial mutations, her hypothesis does not suggest that you don't generate a similarly enhanced rate of deleterious mutations but those are selected against so they are not included in the analysis.In my case I was trying to identify a scenario where there could be a similar tight association between transcription, mutation and selective pressure. The only points I could think of were very early embryonic development and possibly in germ cell maturation and development.TTFN,WK