molecular genetic proof against random mutation (1)

Dear Readers
After reading Spetner's book I realised that all it would take to overthrow NDT is molecular genetic evidence against the mechanisms of random mutation, and examples proving the irrelevance of natural selection in the maintenance of the genome. Scientifically speaking, we need only one example that is not in accord with NDT. It would question the validity of the concepts.
In fact, I already had observed such papers in the scientific literature and I kept them in my collection of "weird stuff".
So let's have a look at this collection and overthrow the concept of random mutation.The first paper I like to discuss with evolutionists is the paper by Schmid and Tautz published in a leading scientific journal (Schmid and K.J. and Tautz, D. A screen for fast evolving genes from Drosophila. Proceeding of the National Academy of Science USA 1997, Volume 94: p9746-9750.). I recommend to look up the paper and read it carefully. In particular, have a close look at the DNA sequences of the 1G5 gene of all presented (sub)species of Drosophila.

A screen for fast evolving genes from Drosophila

[Link to referenced paper added. --Admin]TWO SPECIES OF DROSOPHILA.
The appearance of two species of fruit flies, Drosophila melanogaster and D. simulans, is quiet similar and according to the theory of evolution they became distinct organisms about 10-30 million years ago. In a recent paper by Schmidt and Tautz the exact DNA sequences of rapidly changing genes of both flies were analysed in several subspecies. The focus of the study is on the DNA sequences of the1G5 gene. The 1G5 gene is a unique single copy gene; no paralogue genes are found in both species of Drosophila. It is of unknown function and it exhibits an open reading frame, indicating that it is not a pseudogene. It was selected as subject of the DNA analysis study because it was the fastest changing gene within Drosophila species. The 1G5 gene’s total length of coding region is 1,081 base pairs and it includes only one small intron of 61 base pairs (see chapter 1, gene organisation). In the study an 864 base pair segment, including the intron and exon2, was surveyed for mutations. Thirteen subpopulation of D. melanogaster and four subpopulations of the sibling species D. simulans were analysed for point mutations and other polymorphisms, such as insertion and deletions in this gene.
A number of variable sites are observed in both species. The authors claim that Almost none of the amino acid positions may be under strong selective constraint, because the fraction of polymorphic sites in the intron is comparable to the fraction of polymorphic sites in the coding region. In addition, they say that a comparison between fixed and polymorphic sites between the two species shows also no significant deviation from the assumption of a neutral evolution in this region. Let us have a look at the figure.(If somebody explains to me how to insert a figure, I will fit it in).
Click for larger version[Figure added. --Admin]The figure presents all variable sites in the genes of both species of Drosophila. All polymorphic sites observed in 13 subpopulations of D. melanogaster and 4 subpopulations of D. simulans are shown. The left side of the figure shows the mutations observed in the 61 base pair intron, whereas the right hand side shows mutations in the 803 base pair fragment of exon 2. The exact locations of the mutations in the 1G5 genes are indicated at the top: numbers 141 to 922. All other nucleotides of the genes are identical in both species of Drosophila, and are not presented in the figure.
Only one polymorphic site is observed in the intron (1.6%); the other variable sites are fixed. Similarly, 30 polymorphic sites are observed in exon 2 (3.9%). [if you recount there are not 30 but 31, which may influence the significance of their study].
According to the neutral theory of molecular evolution these data are not significantly different between the number of intron and exon polymorphisms between the two species, implicating neutral evolution within the complete region.It should be noted that evolutionists simply add all polymorphisms of the two species of Drosophila, and than they treat them as one species. In other words they compare apples with pears! They also discriminate between non-fixed (polymorphic) and fixed base substitutions. Obviously, fixed base substitutions are not taken into account. As a result, this biased comparison of distinct species does not say anything about the rate of evolution within one species. All it demonstrates is the difference between two homologous DNA regions of two distinct organisms.Now, let us have an objective look at the data shown in the figure; one that is unbiased by the assumption that the two species of Drosophila have evolved from a common ancestor. Do the genes indeed rapidly evolve, as the authors claim? Two very intriguing phenomena are immediately observed.
Firstly, although introns vary considerably between the species (13 out of 61 nucleotides are different: 21%), introns within subpopulations of D. melanogaster show nearly no variation (1 out of 61 nucleotides vary in only 3 out of 13 subpopulations: 1.6%). Similarly, introns in the 1G5 gene found in the subpopulations of D. simulans do not demonstrate variation at all. This is a very peculiar phenomenon, since the theory of neutral evolution says that the highest incidence of mutations is within the intron regions of a gene. It is assumed that intron regions are not subject to selection, and are able to mutate at random. This is not only expected between species, but also within subpopulations of one species. Yet, we do not see variation within the introns of subpopulations!In addition, have a close look at the positions of the mutations in the introns between the species. The intron exhibits 13 mutations; 10 out of 13 are immediately adjacent to each other (numbers 153-162). The chance that 10 mutations occur at random within an intron of 61 units equals 1.4 x 10(exp)-18. In contrast, the chance that a cluster of 10 adjacent mutations occur in the intron equals 2.2 x 10(exp)-14. Therefore, it is reasonable to assume that the cluster of mutations observed in the introns did not arise by a random mechanism. This is a very important observation, since it is molecular evidence evidence against random mutation. It is, of course, neither mentioned in the text nor discussed!Another remarkable observation is that the 1G5 genes in subpopulations of D. melanogaster, as far apart as Australia, Russia or Canada are completely identical. It implicates a very high level of stability of the DNA sequences within species. Even within the highly unstable 1G5 gene! Of course, proponents of the evolution theory may speculate that these identical populations are derived from a common founder population that got there by coincidence to repopulate the area after an ice age, or so [which is the equivalent of Noah's Ark]. But, why would an Australian and not a Japanese or Mexican population of D. melanogaster - which would make much more sense - take over the empty niches in Russia and Canada? And, it still does not explain the invariable fixed intron in the 1G5 gene of D. simulans, neither the cluster of 10 adjacent mutations in the introns of both species.According to the evolutionary paradigm of common ancestry D. melanogaster and D. simulans became distinct species 10-30 million years ago. It would be expected that one should be able to trace accumulation of mutations in either species to estimate evolution rates within species. Over millions of years only a fraction of variation has been generated within subpopulations of Drosophila melanogaster in the so-called ‘very unstable’ 1G5 gene. In sharp contrast, a lot of variation is observed between the two species. Why does the 1G5 gene within a species stay nearly stable over time, whereas the same genes are highly variable within distinct sibling species? In other words, where is the variation that would be expected within subpopulations of Drosophila diverging towards distinct proteins, for example, separated continents? It is not present.In contrast to what the authors claim, the1G5 gene is not rapidly evolving! It should also be realised that only approximately 30 % of the D. melanogaster genome is polymorph and only 11 % is heterozygous (Page, D.M, and Holmes, E.C. Molecular evolution. A phylogenetic approach. 1998. Blackwell Science Inc. ISBN 0-86542-889-1, p231). These percentages speak for themselves: the major part of Drosophila genes does not vary at all! They are completely stable!I hope for a lot of discussion!Best wishes
Peter

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[This message has been edited by Admin, 07-14-2002]

Dear evolutionists,
This really has to be overthrown,
Peter

Dear John,
That may be so, but as convincingly demonstrated in this reference it violates randomness and thus falsifies NDT.
Soon I will send in falsifiactions of natural selction acting on the genome. I know that the NDT has fallen.
Any questions? Do not hesitate to ask.
Peter

Dear Brad,
Thank you for your response.If a theory can be falsified it is not a good theory, and should be replaced by something else that more accurately describes what we see, even if it has to include design. Only atheists will object to that.
Or to say it in Spetner's words:"There may be good reasons for being an atheist, but the neo-Darwinian theory of evolution isn't one of them" (Spetner,L, Not by Chance, p174).My previous mail was on the falsification of random mutation and the appropriate level is the molecular level. Where else can I falsify this concept?Let's indeed await the metadata. I have already thought of a couple of molecular evolutionary prediction that are expected to be observed. If they are not observed. Q.E.D.Next thing I will prove on this site is that selection is questionable at the level of the genome. I will send in my mail next week and invite you to read "all" recent literature on genetic redundancies. That would improve the discussion.
I am looking forward to your response.Best wishes,
Peter

Dear John,Thanks for you response, but you are wrong.
According to the authors: Almost none of the amino acid positions may be under strong selective constraint, because the fraction of polymorphic sites in the intron is comparable to the fraction of polymorphic sites in the coding region. In addition, they say that a comparison between fixed and polymorphic sites between the two species shows also no significant deviation from the assumption of a neutral evolution in this region.Thus, this gene is not under selective constraint and has not been selected for during millions of years. Unless you would like to assume neutral selection. I have posted a couple of e-mails to evolutionary theorist to figure out what they exacly mean by neutral selection. None of them responded, demonstrating the current problem in NDT.If you have a solution, please let me know.
Peter

Dear Zauruz,
Thanks for your response. I am not from Sweden but originally from The Netherlands.
According to evolutionist the neutral rate of evolution is about 10(exp)-10/nucleotide/year (I will look into it and provide you the exact figures). You are interested in maths, so maybe you can do something with the data.
Have a good one,
Peter

Dear Percy,
Thanks for you response, but I am not impressed by your rebuttal. I mailed this posting because it is a falsification of random mutation.
You did not respond to that.
In response to my observation that randomness is very questionable in this example you state:"First, and as already mentioned, there are still clear limits on permissible mutations within introns. Second, it's not mentioned in the paper because it isn't relevant to their goal of identifying a screen for fast evolving genes".Could you point out where exactly you rebut my observation of "non-randomness of mutations in the 1G5 gene" in the above sentence? I think a lot of readers would also be interested in that.The rest of your rebuttal is not signifcant to this observation. I invite you to explain to me in a scientific way how you solve this problem, then I will respond extensively.(As a matter of fact, this problem cannot be solved unless you assume neutral selection. And that is a contradictio in terminis).I would like to emphasise that NDT is not a fact as long as it can be falsified.Best wishes,Peter

Dear Percy,
Thanks for your response. However, your logic leads to a dead end street: neutral selection.Even if the mechanisms you propose are relevant in the generation of the intron, you have to introduce "neutral (purifying) selection" on this neutral region to explain the intron in the complete population. Since you are so sure, I invite you to explain to me what it is. I mean, what is "neutral selection"?
Best Wishes,
Peter

Dear John,
Thanks for the challenge. I have not thought of it a lot, but I doubt whether linkage can help.
Linkage to genes that improve survival/fitness will still imlpy that redundant genes should change more rapidly. If there is no link between redundancy and gene stability it implies that additional (unknown) mechanisms in genetic stability (and mutation) are involved.
Genetic redundancies end up in a genetic uncertainty problem (See: Tautz, Trends in genetics 2000, volume 16, p475), and disbelief (Nature 415, p8-9, 2002).
The theory can never be proven by science. If anybody falsifies the theory a paradigm-shift is required. I am sure it will be falsified beyond any doubt very soon. I already gave you quite a shock with the 1G5 gene. NDT has now become merely a believe (read Percy's reply).
Best wishes,
Peter

Dear Percy,
I have the impression that you avoid my question.My question: ...."Even if the mechanisms you propose are relevant in the generation of the intron, you have to introduce "neutral (purifying) selection" on this neutral region to explain the intron in the complete population. Since you are so sure, I invite you to explain to me what it is. I mean, what is "neutral selection"?Your answer:....You believe that the sequence of ten differing nucleotides within the intron of the 1g5 gene in Drosophila melanogaster and Drosophila yakuba [simulans, pb] could not have arisen randomly. I offered several possible random sources, but that doesn't mean you are wrong, only that you were leaving out some possibilities.Sorry, but I do not see a link between question and answer. Could you please be more clear.Best Wishes,
Peter

Dear Percy, Dear All
Percy demonstrates by avoiding my question that they are stuck in their own paradigm!
I do not even have to introduce the redundant genes anymore. The paradigm has fallen!!
Dear readers isn't it incredible, the paradigm has fallen!
You are free to believe whatever you like!!!
Dear readers I freeed your minds!!!
The tenet has been overthrown.I wish you all the best,
Peter

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[This message has been edited by peter borger, 07-17-2002]

If you like I'll show you how to falsify natural selection. Better admit that NDT has fallen.
Peter

Dear SLXYou write that:
"At the OCW board, for over a year, you were asked to support your repeated mantras on this issue, and you never provided a single shred of evidence. On the other hand, I and others provided literally DOZENS of citations demonstrating that what the creationist hawks as 'directed mutation' (ala Spetner) are in fact genome-wide hypermutations resulting from oxidative stress. They were not 'directed' at any specific sites. Indeed, the 'discoverer' of the phenomenon, Cairns, after whom the phenomenon was sometimes called, retracted his original conclusions after seeing additional data."I wonder how these data were obtained? Did the authors compare within or between (sub)species? I will affect the outcome. Could you provide me with the references and the sequences that were compared.
I expect DNA damage induced by oxydative stress to be random, since it is expected from oxygen radicals to act randomly. In contrast, mutations in response to the environment may be non-random and involve protein mediated (a) mechanism(s). We know of one mutation generating mechanism involved in antibody improvement. It is thought of as random. However, nobody has had a very close look at it to come to conclusive evidence. It maybe even non-random. I expect it to be non-random since it is protein mediated.
Peter

Dear Admin,
Could you please provide the reference. I have access to Science Magazine. Thanks in advance,
Peter

dear SLPx,
I invite you to have a very close look at all known sequences of the GLO gene. It mutates non-randomly, implying directed mutation (while it is not even functional!). Maybe this is what you are looking for. I also invite molecular biologists to sequence the GLO gene of the (at least) two primates that still synthesize vitamin C. That would shed light on the issue.
Best wishes,
Peter