More non-random evolution

Have alook at radioactivity winds up evolution's clock:http://news.bmn.com/news/story?day=021001&story=2Qoute of the researchers:"Even more intruiging [..] those mutations occurred at positions which have been evolutinary 'hot spots' for the past 60000 years".Non-random mutations? Any comments? Remarks?Best wishes,
Peter

The word random doesn't even appear in the article. The sentence you quoted only notes that, as was already well known, some parts of the genome are more susceptible to mutation than others, and the increased levels of radiation have a greater impact on these "hotspots". Where the mutation takes place is random, but the probability of where the mutation might occur is not equal everywhere.An analogy would be buildings in an earthquake. Which buildings fall is random, but weaker buildings are more likely. Correspondingly, some portions of the genome are more resistant to change than others.--Percy

Dear percy,Radioactivity is assumed to act randomly in the genome with respect to mutations. This is also expected for UV and oxidative stress. Apparently it is not random, as demonstrated by these 'intruiging' findings. What's up? Theory in trouble?
Best wishes,
Peter

borger, perhaps we should stop trying to explain hotspots to you, because its clear you just don't get it.are you suggesting that the mutations caused by radiation are "directed"?or is it simply that some regions of the genome are more susceptible than others to radiation?

dear monkenstick,You say:
borger, perhaps we should stop trying to explain hotspots to you, because its clear you just don't get it.
are you suggesting that the mutations caused by radiation are "directed"?I say:
No, but due to radiation it may be so that the DNA is damaged and an SOS repair sytem is induced that mends the DNA by exchange with a piece of 'Junk DNA' and thus introduces the same nucleotide on the same spot all the time. At least that is a mechanism.You say:
or is it simply that some regions of the genome are more susceptible than others to radiation?I say:
What mechanism do you propose?best wishes.
Peter

Actually, I'm getting a bit tired of the hotspot argument. You're off-base, Peter.Here's one article that specifically directly links a human cancer mutational hotspot at codon 12 of K-ras to preferential DNA damage and poor repair:Denissenko, M., Pao, A., Pfeifer, G. and Tang, M-s. Slow repair of preferentially formed benzo(a)pyrene diol epoxide DNA adducts at the mutational hotspots in the human p53 gene. Oncogene 16:1241-1249 (1998)And here's another one (on line for all you cheapskates): Hatahet, Z., M Zhou, LJ Reha-Krantz, SW Morrical and SS Wallace. 1998. In search of a mutational hotspot PNAS 95: 8556-8561.Hotspots are caused by structural susceptibility at specific points on the DNA to specific mutagens. All evidence suggests that that it is simply a structural defect, and that location and surrounding codons have a major impact on whether a particular DNA site is a "hotspot" or "coldspot". IOW, Peter, there's no god/designer diddling with DNA - just a statistically higher likelihood of mutation caused chemical/structural idiosyncracies and crappy repair.I guess that's one more god/designer of the gaps argument down the toilet.For those interested, here's the full PNAS article referenced in the OP: Natural radioactivity and human mitochondrial DNA mutations. Oddly enough, the article also talks about hotspots being more susceptible, and provides a neat comparison between evolutionary mutations and radiation-induced mutations at the same locus.

What was it about the earthquake analogy that you didn't understand, Peter? Like radiation, earthquakes also act randomly, but not all buildings have equal probability of falling because some are weaker than others.I argued through analogy, while others have explicitly pointed out that some parts of the genome have structural susceptibility to change, and this has all been pointed out to you before. Do you really believe that DNA is equally strong everywhere in the genome? If so, then move the discussion forward by arguing for this point instead of continually restarting the same discussion from the beginning.--Percy

Or perhaps God causes cancer? As noted in Quetzals post.Mark------------------
Occam's razor is not for shaving with.

You fellas got it all wrong - ALL wrong.You see, evidence for hot spots is really evidence for directed mutation.Evidence against directed mutation is REALLY evidence fo rit - you just have to know how to interpret it.Providing requested quotes is is not providing requested quotes, it is bowing to one's god.See? All much clearer now...And besides, Peter Borger is an amazing scientist, and what he says goes, regardless of discipline.

I tried to explain the difference between probabilities to Peter in post 163 on this thread,
http://EvC Forum: molecular genetic proof against random mutation (1) -->EvC Forum: molecular genetic proof against random mutation (1)
but he did not seem to get it. I looked at the 1G5 gene in Genebank and PubMed and can not see what he thinks that he is proveing there either.Peter, I will try to get back to you on both the 1G5 and the GLO gene/scurvy stuff later as I am swamped right now. One note, the rate of depletion of Ascorbate was described in one of the earlier reference papers that I posted for you earlier in the debate, it was a PDF concerning Ascorbate Bioavailability by Levine et al. in PNAS. The lactonase gene inactivation is wrong, not just because there is no mention of it anywhere in the literature, but because inactivation of the lactonase gene product would really screw up a number of other systems as well that an organism would be unlikely to survive (the pentose phosphate shunt for one).------------------
"Chance favors the prepared mind." L. Pasteur
Taz[This message has been edited by Dr_Tazimus_maximus, 10-09-2002]

Dear Taz,You write:
You say:I tried to explain the difference between probabilities to Peter in post 163 on this thread,
http://EvC Forum: molecular genetic proof against random mutation (1) -->EvC Forum: molecular genetic proof against random mutation (1)
but he did not seem to get it. I looked at the 1G5 gene in Genebank and PubMed and can not see what he thinks that he is proveing there either.
Peter, I will try to get back to you on both the 1G5 and the GLO gene/scurvy stuff later as I am swamped right now. One note, the rate of depletion of Ascorbate was described in one of the earlier reference papers that I posted for you earlier in the debate, it was a PDF concerning Ascorbate Bioavailability by Levine et al. in PNAS. The lactonase gene inactivation is wrong, not just because there is no mention of it anywhere in the literature, but because inactivation of the lactonase gene product would really screw up a number of other systems as well that an organism would be unlikely to survive (the pentose phosphate shunt for one).I say:Please do not make a straw man out of the GLO gene. I mentioned several times that I do not need it to demonstrate non-random mutations. That is demonstrated in the 1G5 gene. I also pointed out the implications of non-random mutations for molecular phylogeny in mail #184 in the 'molecular evidence against random mutation-thread'. In addition, it was you who introduced a putative alternative metabolic route for vit C, or a long storage capacity of vit c in the liver. Both mechanism make the gene redundant, and that was my initial claim. That the gene is redundant. According to the hypothesis of 'non-random mutations and a multipurpose genome', redundant genes will be readily inactivated over time, since they are not under selective constraint. That's what we find in primates. Okay, the inactivation is in the same spot, but that may be due to non-random mutations, or if you like 'hot spot' mutations as they are called in literature.best wishes,
Peter[This message has been edited by peter borger, 10-09-2002]

dear Dr Page,I looked up some mitochondrial sequences of several 'primates' and if you like to discuss them, be my guest (PNAS 2001, 98:537-542). I seems that 10 hotspots are present. And, as you know mtDNA doesn't have histons, so that cannot be the explanation. Intriguingly, all mutations are the same nucleotide. So, like the 1G5 gene these mutations are non-random with respect to position and nucleotide. I checked whether they could be 5-methylcytosine hotspots --that converts CG into TA-- and some of them are but the major part aren't. An ununderstood mechanism? I bet it is.Best wishes
Peter

Dear Percy,You say:
What was it about the earthquake analogy that you didn't understand, Peter? Like radiation, earthquakes also act randomly, but not all buildings have equal probability of falling because some are weaker than others.I say:
If so, than it is imaginable that mutations are always introduced at the same spot. And as observed in mtDNA of distinct primates and human subpopulations usually the same nucleotides are introduced. Thus, mutation is non-random with respect to these features and that would bring down the strongest argument for molecular evolution: sequence similarity.You:
I argued through analogy, while others have explicitly pointed out that some parts of the genome have structural susceptibility to change, and this has all been pointed out to you before.
Do you really believe that DNA is equally strong everywhere in the genome?I say:
Apparently mutations are introduced at 'hotspots' that are preserved in humans at least 60000 years. So, how can we discriminate between common descent and common mechanism (whether or not DNA structure related is irrelevant to this observation)?You say:
If so, then move the discussion forward by arguing for this point instead of continually restarting the same discussion from the beginning.I say:
Yes, let's have a close look at the mtDNA's in primates and human.best wishes,
Peter

Peter Borger says: "In addition, it was you who introduced a putative alternative metabolic route for vit C, or a long storage capacity of vit c in the liver. Both mechanism make the gene redundant, and that was my initial claim."But, in conditions of insufficient dietary vitamin C, debility and dead can result. Therefore the gene is not redundant by any alternative genetic or biochemical processes. Therefore, why does not directed mutation correct the "stop" codon mutation and return the gene to activity in stress conditions?"According to the hypothesis of 'non-random mutations and a multipurpose genome', redundant genes will be readily inactivated over time, since they are not under selective constraint. That's what we find in primates. Okay, the inactivation is in the same spot, but that may be due to non-random mutations, or if you like 'hot spot' mutations as they are called in literature."But why is this a common hotspot in almost all of the primates but not all other mammals? Why does the same mutation occur at the "hotspot" in the primate GLO pseudogene? Are hotspots susceptible to repeated occurences of the same mutation? Why is the same common primate mutation not found throughout mammals if this is a hotspot susceptible to a particular nucleotide substitution?I'm afraid your explanation of directed mutation for primate (and human) GLO pseudogenes instead of common ancestry is flimsy.I don't think anyone will argue that all points on a gene have an equal likelihood of mutation. However you wish to extrapolate that this means that there is a directing mechanism which produces these unequal distributions of mutations. You then imply that this means an intelligent design of a multipurpose genome. But why doesn't your directing mechanism act on the multipurpose GLO genome in conditions of scurvy?

Dear WI,Why all these why-questions? How can I do why questions, I'm only human.In the meantime it is a alternative explanation for alignment of mutations found in 'related' species. And maybe you find the evidence flimsy --that is it always how something new starts-- the evidence is NOT zero. So, I have a case.In the meantime I will think about all your why-questions.Thanks and Best wishes,
Peter