molecular genetic proof against random mutation (1)

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Originally posted by peter borger:
Dear Peter,

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Could yo please elaborate a bit on the road. What kind of road? Where does it wind, become unsealed, is a bar nearby, etcetera. That would shed some light on the cause (mechanism) of the accidents.

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best wishes,
Peter

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A wet curving road 50 meters from a bar known for customers who drink heavily. Now can you say exactly at what time and under what conditions in exactly what part of the road the accident will happen?Methylated CpG island 1 Kb upstream of a gene....when exactly will you see the next transition?

Ah, I see that you have yet to post your theory with a testable hypothesis the way I requested for weeks and as I skimmed through the posts of the last week saw that your Nature paper was rejected.As to the second, try something like Current Biology or one of the journals that deals with controversy. Nature and Science only publish high impact material that will get them in the news.You say:
THE MOLECULAR GENAEOLGY OF INTERLEUKIN-1-beta demonstrates an aberration from the species tree. A careful sequence comparison reveals that the human interleukin-1beta gene is more closely related to the mouse than to the homologue genes in pig and sheep. Evolutionists have to admit that this is not in accord with the species tree and postulate that a fourth gene duplication event is required that caused the aberration. Yet, a thorough scrutiny for IL-1-related genes in the human genome doubts that this event ever took place. Eight members of the IL-1 related genes in man’s chromosome 2, to be precise in location 2q11-2q14 (OMIM). Sequence comparison of the IL-1 related genes does not present evidence that a recent duplication of IL-1 beta took place in this region. On the contrary, the family tree of the IL-1 genes clearly demonstrates that the common ancestor copy of the IL-1 beta gene duplicated 3 times maximally, and gave rise to IL-1 alpha and IL-1 beta (Smith, D.E. et al. Four new members expand the interleukin-1 superfamily Journal Biological Chemistry 2000, vol275, pp1169-1175). Thanks to the human genome project, the evolutionary explanation of the aberration of mouse and human IL-1 beta from the species tree can readily be falsified. It should be realised that once a hypothesis is falsified, it remains falsified forever. It cannot be overruled by new experiments, and it doesn't become old-fashioned.
BTW, I discussed this already with Dr page himself and he couldn't address it beyong 'maybe it isn't properly rooted'. So, evolutionists root it properly, otherwise it is a falsification beyon doubt of common descent!Your last sentence demonstrates your desparation Peter. But at least you have given a concrete example. However, there are thousands of genes where species trees and gene trees don't match. Anything horizontally transferred like BovB elements from reptiles to bovids cannot be used as phylogenetic markers. As to your comment about the human genome project and IL-1 beta, so without the respective mouse, sheep and pig genome sequences how can you draw your conclusions? What kind of half assed science do you do in your daily life? You really are a storkist "It should be realised that once a hypothesis is falsified, it remains falsified forever. It cannot be overruled by new experiments, and it doesn't become old-fashioned." Aha, so we should ignore horizontal transfer since Darwin did not know about it and since it is inconvenient for creationists we just say..nah zealotry cannot be overruled..great. I hope nobody invents flying machines that carry people from one destination to another since that would overule gravity and that cannot be done...doh!Ever going to present your hypothesis with the supporting data, how the theory is falsafiable, yada yada yada?I think SLPx's list of creationist posting techniques is very accurate. This is boring. The only creationist who is actually enjoyable to talk to anymore is Tranquility Base at this point.Ciao,Mammuthus

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Originally posted by Joe Meert:
So Borger, when you gonna publish your opus magnum?

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Cheers

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Joe Meert

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******************+To use your term (believe you used it in another thread) it will more likely be an ad hovindom rather than an opus magnum Is he out of jail yet or did he get extra time for sticking an anti-astrologist with a shank

Hi Peter [QUOTE]Originally posted by peter borger:
[B]Dear Mammuthus,You say:
"Ever going to present your hypothesis with the supporting data, how the theory is falsafiable, yada yada yada?"I say:
Good to have you back. How was the holiday? Convention?
*************************************+Thanks. Holiday actually. Went to Spain to tilt at windmills In your absence I presented some sort of hypothesis. It says that all organsims have a multipurpose genome and that adaptations to environment can be induced either randomly, or by non-random protein/RNA mediated mechanism.Problem 1: this is the same old issue of your using an inappropriate definition of random mutation. For example, if a portion of a gene is wrapped around a histone in such a way that it is more or less likely to suffer demethylation it will radically change the probability that you get C to T transitions. However, the C to T transition is still random.Problem 2: Define protein/RNA mediated mechanism of mutation generation. If you mean the lack of proof reading functions of reverse transcriptase for example the higher rate of mutation generated is fully expected and non-random.It holds that there should be a lot of redundant genes in the genome of any organism.Big problem 3: How do random or non random mutation in any way account for redundant genes? There is no connection between the first and second part of your hypothesis. Redundant genes have been known to evolutionary biologists for decades and have presented no problems for the theory. I can think of lots of ways off the top of my head for how do generate duplications and redundancy. And to use your own oft fallacious logic, until you prove each gene is really redundant and not in some way involved in another slightly different funcition your hypothesis is dead That is exacly what we observe. In contrast, the hype of evolutinism doesn't have an explanation for redundant genes.Problem 4: or 3b if you will. This statement is false.So, that in support of my hypothesis.Problem 5: this sentence makes no sense.Furthermore, by now I presented 4 examples that cannot be explained by random mutation, but rather involves non-random mechanisms. These examples are the 1G5 gene, the primate ZFY region, the redundant alpha actinin genes, and today I mailed to SLPx that the DNA shuffling in ticks and lizards is exacly identical. These examples all point in the direction of non-random evolution.Problem 5: On multiple occassions it had been pointed out to you that your definition of non-random is wrong and is in conflict with what statisticians and evolutionary biologists use. That you choose to ignore this fact does nothing to further your cause or support your beliefs.The overturn of an established paradigm takes time, I know.It takes even longer when there is no compelling hypothesis or data with even a billionth of the support evolution has best wishes,
M

quote:

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Originally posted by peter borger:
Dear Joe,

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I am still writing/thinking about my opus magnum. Every now and than, I mail to proevolutionary boards/evolutionary biologists to test some examples/ideas. As you can see from this board the resistance is overwhelming. Of course, I consider all comments carefully since I like to know what to expect, and how to improve it. Prior to launching, better prepare carefully.
Whether or not it will be a scientific publisher depends on guys like Mammuthus and SLPx, since usually such guys comprise the proevolutionary editorial board. Did you know that before Behe published his book it was reviewed by several scientific editors. One of them was against publishing since it would question the current paradigms. Apparently, in his land of evolution there is no freedom of thoughts.

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best wishes,
Peter

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**********************************************************Ah Peter, resorting to personal attacks on my and SLPx integrity as reviewers to further your agenda? I reject papers when the data is bad or the conclusions are not supported by the data. I don't reject papers because an author has a different opionion than I do. I would actually think from your postings that you would be more likely to indescriminatley reject papers that conflict with your religious worldview regardless of the science behind them.Ciao
M

Really Peter...this stuff is not that freakin hard to find out...Henrik did his work on nuclear DNA variation in different populations of humans with 10 kb of an X linked DNA fragment. He then did comparative studies with the great apes...have fun reading...Kaessmann H, Paabo S.The genetical history of humans and the great apes.
J Intern Med. 2002 Jan;251(1):1-18. Review.Kaessmann H, Zollner S, Gustafsson AC, Wiebe V, Laan M, Lundeberg J, Uhlen M, Paabo S. Extensive linkage disequilibrium in small human populations in Eurasia.Am J Hum Genet. 2002 Mar;70(3):673-85.Kaessmann H, Wiebe V, Weiss G, Paabo S.
Great ape DNA sequences reveal a reduced diversity and an expansion in humans.Nat Genet. 2001 Feb;27(2):155-6.Ingman M, Kaessmann H, Paabo S, Gyllensten U.
Mitochondrial genome variation and the origin of modern humans.
Nature. 2000 Dec 7;408(6813):708-13.Kaessmann H, Wiebe V, Paabo S. Extensive nuclear DNA sequence diversity among chimpanzees.Science. 1999 Nov 5;286(5442):1159-62.Kaessmann H, Heissig F, von Haeseler A, Paabo S.
DNA sequence variation in a non-coding region of low recombination on the human X chromosome.
Nat Genet. 1999 May;22(1):78-81.

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Originally posted by peter borger:
Dear Mammuthus,

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If you feel offended: Sorry for that. It happens to me a lot. Try to be a stoic, that helps. And thanks for clearing things and for your comments on the hypothesis. I will take them in consideration. The more scientific comments the better.

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Best wishes
Peter

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*****************************************************I am not offended that easily...however, for someone who started a thread that begins with "Unwarranted conclusions..." it is rather unwarranted of you to claim that you have any idea what criteria I or SLPx use to review manuscripts that land on our desks. That was the only point I wished to make with that specific post.Cheers,
M

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Originally posted by peter borger:
Dear Dr Page,

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It is hard to make links, isn't it?

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In a previous mail you admitted that neutral positions are able to change over time more rapidly than non-neutral position. Kim et al demonstrate that the ZFX region doesn't change at all over 20 million years or so, not even on neutral positions. I find this a bit suspicious. What kind of evolution is this? Non-random evolution? Maybe you can help out?

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Best wishes,
Peter

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***************************Why would the ZFX region be neutral? Destruction of this region would lead to inablitity of the X and Y to pair and thus lead to male sterility and extinction....I would be surprised to find much change at all for this region.

Why would the ZFX region be neutral? Destruction of this region would lead to inablitity of the X and Y to pair and thus lead to male sterility and extinction....I would be surprised to find much change at all for this region.MY RESPONSE:The ZFX gene has about 20% neutral positions on third codon position. No variation in these position during 20 million years simply overturns molecular evolution. Today is just another bad day for evolutionism, I guess.Best wishes,
Peter
*************************ZFX is not so static as you make it seem Mol Biol Evol 2000 May;17(5):804-12 Related Articles, LinksSex chromosomal transposable element accumulation and male-driven substitutional evolution in humans.Erlandsson R, Wilson JF, Paabo S.Max-Planck-Institute for Evolutionary Anthropology, Leipzig, Germany. riker1@biochem.kth.seWe sequenced the genomic region containing the human Y-linked zinc finger gene (ZFY). Comparison of ZFY to the related region on the X chromosome (ZFX) and to autosomal sequences reveals a significant accumulation of transposable elements on the sex chromosomes. In addition, five times as many retroviruslike elements (RLEs) are present in the ZFY region as in the ZFX region. Thus, transposable elements accumulate more rapidly on the sex chromosomes, and the insertion of RLEs may occur more frequently in the male than in the female germ line. When the accumulation of substitutions in Alu elements was analyzed, it was found that the Alu elements at the Y-chromosomal locus diverged significantly faster than those at the X-chromosomal locus, whereas the divergence of autosomal Alu elements was intermediate. The male-to-female mutation rate ratio was estimated to be 2.5.

Since Peter ignored it (and most of my comments) the last time I bump this again....

quote:

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Originally posted by Mammuthus:
Why would the ZFX region be neutral? Destruction of this region would lead to inablitity of the X and Y to pair and thus lead to male sterility and extinction....I would be surprised to find much change at all for this region.

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MY RESPONSE:

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The ZFX gene has about 20% neutral positions on third codon position. No variation in these position during 20 million years simply overturns molecular evolution. Today is just another bad day for evolutionism, I guess.

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Best wishes,
Peter
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ZFX is not so static as you make it seem

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Mol Biol Evol 2000 May;17(5):804-12 Related Articles, Links

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Sex chromosomal transposable element accumulation and male-driven substitutional evolution in humans.

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Erlandsson R, Wilson JF, Paabo S.

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Max-Planck-Institute for Evolutionary Anthropology, Leipzig, Germany. riker1@biochem.kth.se

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We sequenced the genomic region containing the human Y-linked zinc finger gene (ZFY). Comparison of ZFY to the related region on the X chromosome (ZFX) and to autosomal sequences reveals a significant accumulation of transposable elements on the sex chromosomes. In addition, five times as many retroviruslike elements (RLEs) are present in the ZFY region as in the ZFX region. Thus, transposable elements accumulate more rapidly on the sex chromosomes, and the insertion of RLEs may occur more frequently in the male than in the female germ line. When the accumulation of substitutions in Alu elements was analyzed, it was found that the Alu elements at the Y-chromosomal locus diverged significantly faster than those at the X-chromosomal locus, whereas the divergence of autosomal Alu elements was intermediate. The male-to-female mutation rate ratio was estimated to be 2.5.

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quote:

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Originally posted by peter borger:
Dear mammuthus,

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You posted:

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Originally posted by Mammuthus:
Why would the ZFX region be neutral? Destruction of this region would lead to inablitity of the X and Y to pair and thus lead to male sterility and extinction....I would be surprised to find much change at all for this region.
MY RESPONSE:

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The ZFX gene has about 20% neutral positions on third codon position. No variation in these position during 20 million years simply overturns molecular evolution. Today is just another bad day for evolutionism, I guess.

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Best wishes,
Peter
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ZFX is not so static as you make it seem

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Mol Biol Evol 2000 May;17(5):804-12 Related Articles, Links

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Sex chromosomal transposable element accumulation and male-driven substitutional evolution in humans.

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Erlandsson R, Wilson JF, Paabo S.

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Max-Planck-Institute for Evolutionary Anthropology, Leipzig, Germany. riker1@biochem.kth.se

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We sequenced the genomic region containing the human Y-linked zinc finger gene (ZFY). Comparison of ZFY to the related region on the X chromosome (ZFX) and to autosomal sequences reveals a significant accumulation of transposable elements on the sex chromosomes. In addition, five times as many retroviruslike elements (RLEs) are present in the ZFY region as in the ZFX region. Thus, transposable elements accumulate more rapidly on the sex chromosomes, and the insertion of RLEs may occur more frequently in the male than in the female germ line. When the accumulation of substitutions in Alu elements was analyzed, it was found that the Alu elements at the Y-chromosomal locus diverged significantly faster than those at the X-chromosomal locus, whereas the divergence of autosomal Alu elements was intermediate. The male-to-female mutation rate ratio was estimated to be 2.5.

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MY RESPONSE:

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I didn't forget about this reference. I read it last weekend and the content of the article simply doesn't rebut my observation that the ZFX gene is completely stable during '20 million' years. That there are genetic elements jumping around in the genome and accumulate on the X chromosome in this region is in accord with the vision of a multipurpose genome where variation is induced by such elements, not by accumulation of SNPs or other mutations. These jumping elements affect gene expression and thus induce phenotypic variations.

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Best wishes,
Peter

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*****************************************Hi Peter,
However, that is completely false...the ZFX region is NOT completely stable. There is also a ZFY microsatellite that varies and is used in studying evolution of male lineages. Thus, your argument that ZFX/ZFY is absolutely stable is falsified.PB
"These jumping elements affect gene expression and thus induce phenotypic variations"M: However, there is no evidence for this...most elements do nothing. However, even if retrotranposition events were the only mutations occurring..they are still significant mutations and a major component of genetic variability. And there is extremely strong selectional constraints in the ZFX/ZFY regions because destroying this region would prevent XY chromosomal pairing thus limited diversity in this region is fully expected by evolutionary theory. oh yes, and you ignored the following...from Erlandsonn et al. "When the accumulation of substitutions in Alu elements was analyzed, it was found that the Alu elements at the Y-chromosomal locus diverged significantly faster than those at the X-chromosomal locus, whereas the divergence of autosomal Alu elements was intermediate. The male-to-female mutation rate ratio was estimated to be 2.5." Thus SNP's and other mutations that you dismissed for this region are happening at a nice clip.So the data are not compatible with your Lamarkian pseudo pre-adaptation hypothesis.Hopefully we can continue to discuss some of the other points as well.Best wishes,
M

quote:

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Originally posted by peter borger:
Dear Mammuthus,
Thanks for the swift reponse, but could you please point out where exactly your reference falsifies the observation that the ZFX gene is completely stable, i.e. NO mutations on neutral positions. According to molecular evolution variation is expected to be found on these silent positions.

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M:
Hi Peter,
"When the accumulation of substitutions in Alu elements was analyzed, it was found that the Alu elements at the Y-chromosomal locus diverged significantly faster than those at the X-chromosomal locus, ...what is it here that you do not understand regarding substitutions at neutral positions?

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PB:
In addition, you suggest that the invariability may be due to alignment of X and Y chromosome during cell divisions. Although it could potentially explain non-variablity within species, it doesn't explain the non-variability between the primates. Besides, a couple of weeks ago you mailed references regarding these regions and it turned out that they are not at all crucial for chromosomal alignment, since several species simply lack them ( for instance marsupials if I recall properly).

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M: First, I am not claiming it is the only reason for primate speciation. However, the region is more similar among primates as they are related and the region is similar within primate groups because it is conserved.....and the region is critical for chromosomal alignment..try pairing a marsupial X with mammalian X chromosome of choice. The reference to marsupials had to do with the content of the X chromosomes by the way and not ZFX if I recall. Marsupials have a large chunk of eutherian X linked genes on their autosomes.

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PB:
Bottomline is, you still didn't rebut the observations of high stability of the ZFX gene. In my opinion its is a 'inert DNA location', i.e. mutations have never been 'dragged' to this spot. (Q: Dragged by what? A: Unknown mechanism/force?)

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M: This last paragraph makes no sense. The region is not inert (whatever that means). And I have not suggested that mutations are dragged there...rather most large scale mutations are not tolerated and are selected out....not an uknown mechanism or force....but I am not sure what you where trying to say in the last paragraph...could you elaborate.

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Cheers,
M

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Peter

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Dear Dr Page,
Often I have the feeling that I am waisting my time here on this board. If you for instance started to look up the papers I refer to, it certainly would improve our discussion.M: I and other start to feel the same way when you persist in the fallacy of non-random mutations. If your hypothesis is going to have any merit it will have to stand on being falsifiable, testable, and supported by data. Not by changing defintions to suit your hypothesis needs.cheers,
M

quote:

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Originally posted by peter borger:
Dear Peter,

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Why don't you have look at the sequences of the 1g5 gene in drosophila subspecies or the mtDNA sequences in subspecies of ancient human. You will discover --like me-- that there are two types of mutations: random and non-random with respect to nucleotide and position. The latter will give the illusion of common descent. (also read mail #185). Why not look at these sequences for yourself, instead of reiterating that I am wrong. I guess, it has been overlooked, since usually DNA sequences of subspecies are not presented. I recommnend you to do a bit of research yourself and demonstrate that I am wrong. Back it up with scientific publications. Till now nobody showed me a study that rebuts my claim beyond doubt.

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Best wishes,
Peter

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**************************Alas I have rebutted your claim repeatedly. Look at the distribution of mutations and you will get a normal distribution. There are lots of human population genetics studies. I have referenced them before. That you continue to deny they exist is your fallacy. The burden of proof is on you Peter. I study ancient DNA and I know the study you are referring to well (in fact a colleague of mine wrote a piece in Science demonstrating several technical fallacies in the study). In no way based on the ancient sequence could you then determine where the next mutation would occur in the next human lineage or in the next generation. If you found Mungo lakes fellow villager, you cannot tell me exactly where the mutations in his mtDNA would be. That a particular kind of mutation occurs more frequently(i.e. transitions) does not make it a non-random mutation. That all of your hypotheses are based on a deterministic mutation mechanism falsifies them a priori as what you claim is not observed.Where exactly, not probably, will the next mutation occur in my HV1 region?

PB:
I say:
No, you didn't rebut the 1G5 gene in drosophila and you didn't rebut the line up of non-random mutaions in ancient mtDNA. You only keep repeating yourself that I have to predict were and when the next mutation in your HV1 region will occur. I already did a prediction for that, but you are still not content. In the meantime i gave you the new definition of non-random mutations [science is about adapting hypotheses, isn't it?], since the concept of deterministic mutations is presently not proven. But evidence is at close hands (see Dr Page's mailing: Cairns excerpt. I invite also Dr Page to rediscuss this topic since I discovered some 'strange stuff' in this mailing).M: You have not provided one single piece of evidence for a deterministic (non-random) mutation Peter. That transitions occur more frequently than transversions is all you have shown...WOW big freaking discovery Peter...how many decades has this been known?!?
In what concievable way does this violate principles of molecular evolution???I say:
What you fail to acknowledge is that there are two types of mutations: random and non-random, and added together they give the impression of randomness. Only in extreme cases one can observe them
seperately, since usually the are obscured by random muations. Still one can observe them in the 1G5 gene.M: I do not acknowledge your fairy tales. Where will the next mutation occur in 1G5 in the next generation? You cannot tell me that either much less for HV1. It is not a pre-determined mutation fate as you would wish to believe.PB:
It is proof that they exist
and all you do is deny it and present me data from which it is not immediately clear what the random and non-random muations are. But even in the mtDNA study I referred to it is clear (as pointed out). Furthermore, there is still the invitation to discuss this example in detail and I will show you where it violates evolutionism. It can be demonstrated that these data violate 1) common decent, 2) random mutation, and 3) molecular clock. Open a new thread for it, and I will once more beat evolutionism.M: If it is so easy do it here.
1) How does it violate common descent...surely you can show this in a few sentences
2) Show how it violates random mutation
3) I don't buy molecular clocks anyway because of the number of variables that can knock the clock off pace so go ahead and violate that one...it says nothing about the validity of evolution.PB:
Technical fallacies that gave rise to the wrong sequences? If not, the example still stands and your attemp to rebut are void. But now I get it, your colleague also discovered that the data violate evolutionism and therefore the study cannot be correct. Isn't that the way it works. If studies appear in the journals that violate the hype the studies are wrong? Is that it?M: Unwarranted conclusions prickly Peter
They failed to reproduce the ancient sequences in a separate laboratory and the sequence they got was most similar to an mtDNA pseudogene hence they have not discounted the possibilty that they have a modern DNA contamination. That is the flaw in the paper which was pointed out by Cooper et al. As to the analysis with regard to random mutations, that part is fine. It is only the origin of the Mungo lake sequence that is in doubt. And if it is a mtDNA pseudogene it is still of great interest to see how homologous sequences diverge under different selection regimes and with a different set of DNA repair enzymes affecting their respective mutation rates...but then you of course knew that there is a whole sub discipline that researches this topic didnt you?PB:
And again you try it. How many times do I have to reiterate myself on non-random mutations and what the may implicate for evolutionism? There we go again. By non-random I mean with respect to nucleotide and position. They will give the illusion of common descent. I already presented scientific evidence for the existence of these mutations so what's the point? O, now I get it, it overturns the strongest molecular argument for commmon descent. Well, I could care less.M: You have not Peter. You have failed to provide evidence of a deterministic mutation. You wish for it to be deterministic so you merely claim that higher transition than transversion frequency or the fact that dozens of prolines don't suddenly appear in most proteins is evidence of a deterministic process rather than selection against such mutation events or the freaking basic chemistry of nucleic acids i.e. C to T transitions. However, you have failed to demonstrate a mutation pre-adapting to an environmental pressure that does has not occurred yet, the organism then surviving due to that pre-emptive mutation and surviving i.e. Lamark. However, a large number of studies have shown that you can cause infrequent variants in the population to become frequent because of selection because those lacking said trait fail to pass on their genotype. Similarly, it is possible both experimentally and in the wild to see fixation by genetic drift....Where is your evidence of a multipurpose Lamarkian genome? You keep claiming it is so easy to show this yet you have not answered most of my posts addressing your hypothesis, dodged Quetzals refutation of your W. nobilis example, and have otherwise repeated the same mantra over and over.Answer here or start another thread as you see fit.Cheers,
M