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

quote:

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Originally posted by peter borger:
These percentages speak for themselves: the major part of Drosophila genes does not vary at all! They are completely stable!

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Assuming the conclusion quoted above whether correct or not, why is this a problem?The flies happened upon a combination that works and has continued to work for millions of years. As long as it works it will be selected for, thus dampening the genetic drift/mutation. Please note that the gene studied is of UNKNOWN function not 'has no function'.------------------
www.hells-handmaiden.com

Heavy stuff, Borger!Do you know how many mutations per amount of DNA that occur to every next generation of an organism? Approximatelly.Are you from Sweden by the way?

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

quote:

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Originally posted by peter borger:
That may be so, but as convincingly demonstrated in this reference it violates randomness and thus falsifies NDT.

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No it doesn't, not if that particular gene has been SELECTED FOR all these millions of years. Has it been selected for? I don't know, and apparantly neither does anyone else at the moment, since the function of the gene is unknown.------------------
www.hells-handmaiden.com

Even if you are able to falsify selection on a genotype within your genome orthoselection could still occurr. The condition would be rather that neither phenotype nor geneotype were supported by the database but we do not have even metadata to provide for this vision if I am currently uptodate. There could be a turn nonetheless in this logic which would not per say be "falsifiable" (past tense of falsify) in any sense of the word.

On the same basis I was not disabused inter alia of John Morris setting up a BIBLICAL bias. There is more to the C/E use of Dobshanksy than the one sentence in your post that passes on without the confusion in DObshansky's thought of the tree of life. Merely talking on molecular terms does not make this terminal ring species disappear. One needs a more profound historical synthesis than Provine provided and he spent 13 yrs building his last one.

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

A link to the paper and to the figure you reference have been added to your original post by the Admin, making it easier to actually comment on the contents of your post.

peter borger writes:

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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...

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That mistakes occur in transmitting the genetic code from one generation to the next has been established beyond any reasonable doubt.

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Scientifically speaking, we need only one example that is not in accord with NDT. It would question the validity of the concepts.

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It would only "question the validity of the concepts" if it were a mechanism contradicting NDT, not merely missing from it.

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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.).

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You draw conclusions from this paper in areas unrelated to the issues it addresses. Certainly the authors wouldn't agree with you.

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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!

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If you're talking about the figure, the authors do not add the polymorphisms together, they merely present them in the same table for comparison. Since the two species share a recent common ancestor, genetic similaries are expected, and the table shows this. If the two species were really as different as apples and algae (I can't use your analogy of apples and pears, since they, too, share a recent common ancestor) then they wouldn't even share this 1G5 gene.

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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.

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And this is why you shouldn't attempt to draw conclusions outside the specific topic of paper. As the title of the paper clearly states, there were developing a screening technique for identifying fast evolving genes within the Drosophila genome. Their technique evidently requires ignoring base substitutions. You can't draw conclusions about the consistency of the Drosophila genome with mutational theory from this paper.

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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!

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First, while introns are not expressed in the organisms phenotype, there are still clear limits on permissible mutations. In particular, they have to remain recognizable as introns else they may result in expression, which would be equivilent to a massive multi-nucleotide polymorphism and probably catastrophic to the organism.Second, and orthogonal to the first point, with a data set of two introns your conclusions have practically zero statistical significance. The authors conclusions are inconclusive for the same reasons. Replication of this process by other scientists using other genes must be performed before, over time and only if congruent results are obtained, the author's results can become generally accepted.

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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!

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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.

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Another remarkable observation is that the 1G5 genes in subpopulations of D. melanogaster, as far apart as Australia, Russia or Canada are completely identical.

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But don't forget the relatively local differences, such as between populations in Australia, and between populations in the US. Without speculating as to possible reasons, it doesn't seem like either simple migration or Noah's Ark account for it very well.

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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.

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Uh, nothing else would make sense. Naturally there are fewer genetic differences within a species than between species.

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Why does the 1G5 gene within a species stay nearly stable over time, whereas the same genes are highly variable within distinct sibling species?

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The paper is about identifying fast evolving genes, and 1G5 was chosen because it is precisely that, a fast evolving gene. As they state in the introduction, the fast evolving genes were identified by comparison with Drosophila virilis, which is thought to have diverged with Drosophila melanogaster some 40-60 million years ago. They then compare the IG5 gene of Drosophila melanogaster with Drosophila yakuba, divergence thought to be 10-15 million years ago, in order to test their hypothesis that "under a neutral model of molecular evolution that a gene that shows a high divergence rate between species should also be polymorphic within a species."In other words, the identification of fast evolving genes does not derive from the data in Figure 1. If you're trying to figure out how they identified fast evolving genes from this data you are doomed to failure because this is not the data they used. As far as I could tell, they don't actually present this data in the paper.These misinterpretations suggest that a reassessment of your conclusion that the Drosophila genome is "completely stable" might be appropriate.

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It should also be realised that only approximately 30% of the D. melanogaster genome is polymorph and only 11 % is heterozygous. These percentages speak for themselves: the major part of Drosophila genes does not vary at all! They are completely stable!

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Uh, without rate information the percentages mean nothing, and certainly 30% polymorph implies considerable variability for which you need some kind of source.--Percy

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

peter borger writes:

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Thanks for you response, but I am not impressed by your rebuttal.

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Charmed, I'm sure!

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Could you point out where exactly you rebut my observation of "non-randomness of mutations in the 1G5 gene" in the above sentence?

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You're referring to the continguous set of nucleotide differences in the intron of 1G5? If so, you made a lot of points, and I addressed a lot of points. Is this one you feel is key?The possibility I mentioned previously was that you don't know what the requirements of the intron are. There may be limitations on where changes can be made in the intron without causing disruption of its very behavior as an intron.There are of course other possibilities. Heads *can* come up ten times in a row. The substitution may have been a single, large replication error. I'm sure there are other possibilities. You can't conclude non-randomness from the data available. This was not a topic the paper even remotely addressed, you're just using it to mine data.It appeared to me that your primary claim was that the 1G5 gene exhibited relative stability between Drosophila melanogaster with Drosophila yakuba, when in reality the paper used that gene because it exhibited fast evolution when Drosophila melanogaster and Drosophila virilis were compared. The data for that comparison isn't present in the paper.--Percy

quote:

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Originally posted by peter borger:
Dear John,

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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.

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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.

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If you have a solution, please let me know.
Peter

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It seems that this thread has been picked up by Percipient who is doing a better job of it than I could, but two things came to mind after reading your last reply to me.The first is that this gene may be linked to other genes which are under selective pressure. One of the authors, Tautz, proposes this possibility in another paper. He refers to it as a weak selection.The second is that even assuming this gene has not been under selective pressure and has not mutated, you still have not proven your point. There is no minimum random mutation rate per gene. You have one gene in one organism, this is one case in many. You could be looking at a fluke. A run of luck at the roulette wheel does not prove the odds have changed.------------------
www.hells-handmaiden.com