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Author | Topic: Doe the climate direct mutations towards the ATP6 gene? | |||||||||||||||||||||||
peter borger Member (Idle past 7695 days) Posts: 965 From: australia Joined: |
Dear All,
A very interesting paper can be found in a recent issue of PNAS (dec 2002): Just a moment... It is my persional opinion that the mutations to the ATP6 gene could have been directed to this region of mitochondrial DNA (Trigger: temperature? geographical altitude? other?). In particular, the native American Indians are only around for few thousands years in the colder area of the northern part of the American continent. In my view, a couple of hundred of generations does exclude a utterly random mechanism of mutaions and selection. I prefer a NONRANDOM mechanism and SELECTION. In other words the GUToB. Any ideas? Best wishes,Peter 'Let's find more evidence for the GUToB'
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judge Member (Idle past 6474 days) Posts: 216 From: australia Joined: |
quote: Don't know if this helps...but I'm sure if it's no good natural selection will ruthlessly deal with it! "It is difficult to imagine how bacteria are able to solve complex problems like these - and do so without, at the same time, accumulating a large number of neutral and deleterious mutations - unless they have access to some reversible process of trial and error." Adaptive mutations appear to be directed in non-growing cells to sites that allow growth. from...SIUC University Carbondale
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Peter Member (Idle past 1509 days) Posts: 2161 From: Cambridgeshire, UK. Joined: |
Not all of us have access to that, could you summarise for us?
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PaulK Member Posts: 17828 Joined: Member Rating: 2.5 |
quote: The abstract is available for free access - and the authors conclude that the difference is probably due to selection (and the summary in the abstract makes that look more likely than Peter's non-random mutations) "However, it is not easy to account for the fact that only two mtDNAlineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia." "African mtDNA variation did not significantly deviate from the standard neutral model..." "Comparison of the ka/ks ratios for each mtDNA gene from thetropical, temperate, and arctic zones revealed that ATP6 was highly variable in the mtDNAs from the arctic zone, cytochrome b was particularly variable in the temperate zone, and cytochrome oxidase I was notably more variable in the tropics. Moreover, multiple amino acid changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be functionally significant.From these analyses we conclude that selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate."
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peter borger Member (Idle past 7695 days) Posts: 965 From: australia Joined: |
dear peter,
The abstract: Natural selection shaped regional mtDNA variation in humans. Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC. Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, 92697-3940, USA. Human mtDNA shows striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that only two mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative to drift, natural selection might have enriched for certain mtDNA lineages as people migrated north into colder climates. To test this hypothesis we analyzed 104 complete mtDNA sequences from all global regions and lineages. African mtDNA variation did not significantly deviate from the standard neutral model, but European, Asian, and Siberian plus Native American variations did. Analysis of amino acid substitution mutations (nonsynonymous, Ka) versus neutral mutations (synonymous, Ks) (kaks) for all 13 mtDNA protein-coding genes revealed that the ATP6 gene had the highest amino acid sequence variation of any human mtDNA gene, even though ATP6 is one of the more conserved mtDNA proteins. Comparison of the kaks ratios for each mtDNA gene from the tropical, temperate, and arctic zones revealed that ATP6 was highly variable in the mtDNAs from the arctic zone, cytochrome b was particularly variable in the temperate zone, and cytochrome oxidase I was notably more variable in the tropics. Moreover, multiple amino acid changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be functionally significant. From these analyses we conclude that selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate. Best wishes,Peter
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peter borger Member (Idle past 7695 days) Posts: 965 From: australia Joined: |
Dear Paul,
PK: The abstract is available for free access - and the authors conclude that the difference is probably due to selection (and the summary in the abstract makes that look more likely than Peter's non-random mutations) PB: It is known that amerindians only recently migrated to the arctic zone of Northern America. If we take an overestimated date of 10 ky BP (more realistic is <5 edit]: The fact that the ATP6 gene is a socalled highly concerved gene (e.g. no variation on neutral positions) may indicate that there is another code present in these genes ('REDUNDANT genetic code', and not 'degenerate genetic code', since it is NOT degenerate) that determines that this gene may be subject to directed mutations. And, once again, selection is not the discussion here. It is also part of the GUToB. The matter is whether or not mutations are random or NON random. Apparently, they are nonrandom. Best wishes,Peter [This message has been edited by peter borger, 01-20-2003]
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PaulK Member Posts: 17828 Joined: Member Rating: 2.5 |
[QUOTE]Originally posted by peter borger:
[B]Dear Paul, PK: The abstract is available for free access - and the authors conclude that the difference is probably due to selection (and the summary in the abstract makes that look more likely than Peter's non-random mutations) PB: It is known that amerindians only recently migrated to the arctic zone of Northern America. If we take an overestimated date of 10 ky BP (more realistic is <5 imagine.) [\QUOTE] The Amerindians emigrated to the Americas via Siberia. You neglect to consider time in Siberia, and you offer no evidence for direction of mutations.
[QUOTE]
[added by edit]: The fact that the ATP6 gene is a socalled highly concerved gene (e.g. no variation on neutral positions) may indicate that there is another code present in these genes ('REDUNDANT genetic code', and not 'degenerate genetic code', since it is NOT degenerate) that determines that this gene may be subject to directed mutations. [\QUOTE]The actual phrase is "more conserved" implying that variation is lower than expected. It could equally well indicate selection. [\QUOTE]And, once again, selection is not the discussion here. It is also part of the GUToB. The matter is whether or not mutations are random or NON random. Apparently, they are nonrandom. [\QUOTE] In other words we should ignore the conclusions of the paper, assume that selection is not a factor and then conclude non-random mutations. So that is what evidence for your GUToB coms down to. Assume that natural selection doesn't happen and then conclude that your mechanism is the only alternative. I am not impressed.
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judge Member (Idle past 6474 days) Posts: 216 From: australia Joined: |
PaulK:
In other words we should ignore the conclusions of the paper, assume that selection is not a factor and then conclude non-random mutations. So that is what evidence for your GUToB coms down to. Assume that natural selection doesn't happen and then conclude that your mechanism is the only alternative. I am not impressed. Judge:Hi!..So do you think selection could explain this? If so can you provide some rough figures? And if selection doesn't sem to fit the data, and you don't agree with PB's theory then what alternative do you propose? Thanks.
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Quetzal Member (Idle past 5902 days) Posts: 3228 Joined: |
Hi Judge:
quote:I think that selection would seem to be indicated here. I don't know about coming up with a formula, but the fact that there was apparently variation based on climatic zone would tend to favor that explanation. Note that the data reported indicated ATP6, for instance, was more variable in the arctic, whereas cytochrome b was more variable in the temperate zone, etc.
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peter borger Member (Idle past 7695 days) Posts: 965 From: australia Joined: |
Dear Paul,
The human mtDNA contains 16.569 nucleotides, the estimated mutation rate for mtDNA is about 1 every 300-600 generations. Even if it took 100 Ky to migrate from Asia to America, random mutations wouldn't do the trick. NB: to determine this mutation rate evo's compare human and chimpanzee mtDNA and adjusting the differences over a period of 5 million years (for obvious evoreasons). They estimated the average mtDNA mutation rate to be one mutation for every 300 to 600 generations of 20 years. ("Calibrating the Mitochondrial Clock," by A. Gibbons, Science January 2, 1998). Best wishes,Peter "2003 marks the end of evolution theory. Welcome, GUToB"
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judge Member (Idle past 6474 days) Posts: 216 From: australia Joined: |
Queztal:
I think that selection would seem to be indicated here. I don't know about coming up with a formula, but the fact that there was apparently variation based on climatic zone would tend to favor that explanation. Note that the data reported indicated ATP6, for instance, was more variable in the arctic, whereas cytochrome b was more variable in the temperate zone, etc. judge:Hmm.. I did reply to this but it doesn't seem to have shown up (could be my fat fingers hitting the wrong key again) Anyway thanks for the reply . I haven't posted here much bu I have read through a lot and have enjoyed your posts. Hypothetically could this variation also be explained by NRM, due to the different climates? (all things being equal). How might we discriminate between the two? Again, all things being equal (and of course it never is) would not the number of generations proposed perhaps indicate NRM rather than random mutation and selection?
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Peter Member (Idle past 1509 days) Posts: 2161 From: Cambridgeshire, UK. Joined: |
quote: I thought that figure was for unselected regions? ...and don't creationists keep saying its more like 1 in 40generations anyhow (Tsar Nicholas II analyses and all that)?
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peter borger Member (Idle past 7695 days) Posts: 965 From: australia Joined: |
Dear Peter,
quote:-------------------------------------------------------------------------------- Originally posted by peter borger: Dear Paul, The human mtDNA contains 16.569 nucleotides, the estimated mutation rate for mtDNA is about 1 every 300-600 generations. Even if it took 100 Ky to migrate from Asia to America, random mutations wouldn't do the trick. NB: to determine this mutation rate evo's compare human and chimpanzee mtDNA and adjusting the differences over a period of 5 million years (for obvious evoreasons). They estimated the average mtDNA mutation rate to be one mutation for every 300 to 600 generations of 20 years. ("Calibrating the Mitochondrial Clock," by A. Gibbons, Science January 2, 1998). Best wishes,Peter "2003 marks the end of evolution theory. Welcome, GUToB" -------------------------------------------------------------------------------- P: I thought that figure was for unselected regions? ...and don't creationists keep saying its more like 1 in 40generations anyhow (Tsar Nicholas II analyses and all that)? PB: You are right. The figure produced by evo's and published (!!) in science is ludicrous. I already demonstrated that if you have a look in mtDNA from ancient man human and chimp have an ancestor 150 ky BP.It is another sleight of hand to keep up the appearance of evolutionism: add one chimp in a human analysis and their data fit again. It is NON-SCIENCE. For evidence see the reference (PNAS dec 2002) Anyway, you have to beat them with their own published data, whatever ludicrous they may be. You are starting to see. Best wishes,Peter [This message has been edited by peter borger, 01-22-2003]
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Quetzal Member (Idle past 5902 days) Posts: 3228 Joined: |
Hi Judge:
quote:Good questions! 1. I think there's a difference here between non-random mutation and directed mutation. Non-random in the sense that the article quoted refers to the higher likelihood of directional selection on ATP synthase subunit 6 in arctic as opposed to subarctic mtDNA. To give you a better feel for why this makes sense, I'll quote from the article itself:
mtDNA variation would be the ideal method to foster adaptation to different environments. Mitochondrial oxidative phosphorylation (OXPHOS) uses dietary calories to generate ATP to do work and heat to maintain body temperature. The balance between these two functions is determined by the efficiency of coupling the mitochondrial inner membrane electrochemical gradient to synthesize ATP through the ATP synthase. Variants that reduce the coupling efficiency would reduce ATP production, but increase heat production. Such variants would be advantageous in the subarctic and arctic where survival of cold stress would be a major factor in survival. Partial uncoupling of the mitochondria would increase the basal metabolic rate of the individual and hence would require a higher caloric intake, such as that provided by a high-fat diet. Thus, mtDNA ATP6 variants that reduce coupling might partially account for the increased basal metabolic rate that has been observed in indigenous, circumpolar, human populations. As you can see, there IS an adaptive explanation, that is non-random in the sense that environmental (selection pressures) favor the fixation of mutations that are beneficial in the particular environment. BTW: The article provides a rather nice molecular explanation for the observations that have come to be known as "Allen's Rule" and "Bergmann's Rule" concerning anatomical differences between tropical and polar populations/species. The high mutation rate of mtDNA and the central role of mitochondrial proteins in cellular energetics make the mtDNA an ideal system for permitting rapid human and animal adaptation to new climate and dietary conditions. The uniparental (maternal) inheritance of the mtDNA favors the rapid segregation, expression, and adaptive selection of new advantageous mtDNA alleles. The lack of recombination would mean that selection of beneficial mutants would increase the frequency of the entire mtDNA haplotype through hitchhiking. Hence, climatic selection would lead to the regional-specific haplogroups that are observed. The above does NOT equate to directed mutation (as PB, for instance, means when he says "non-random"), which refers to the action of an unidentified mechanism which causes a mutation to occur fortuitously in a genome that engenders a phenotypical change favorable to the organism in its new environment (a cart-before-the-horse problem). One of the reasons that obesity, neurological disorders, etc are becoming prevalent is that people who have inherited mtDNA sequences originally adapted for a particular environment are now finding those mutations - formerly beneficial - are now maladaptive. If directed mutations existed, it would seem to me that a reversal or new "non-random mutation" would create a successful adaptive response to new lifestyles, diet, climate constraints, etc. 2. Discriminating would be difficult, IMO. You'd have to set up an experiment (obviously on some fully sequenced non-human organism) that excluded all other variables. Then apply a particular climatic (for instance) pressure and see if the identical mutation developed consistently in response. If it did, you might have the beginnings of a research avenue on directed mutation. You'd have to make sure that it wasn't just random, and I'm not sure how you'd do that. I guess I would be willing to accept the results if it could be shown, but without a replicatable mechanism I think NRM simply multiplies assumptions without providing any additional explanatory power. 3. Again, I'm not sure how many generations it would take one way or the other. A lot depends on the actual mutation rate. Since they've just discovered the regional variation, I'm not sure anyone knows. I'd say at the least the article shows there may be some rethinking required on the current "molecular clock" timing - when Mammuthus gets back next week, I'll ask him (he's agin' the whole clock thingy anyway).
quote:Likewise. My New Year's resolution was to stay out of philosophy discussions - but I have been following your posts. I enjoy your clear, lucid style (even tho' I might not agree with you ). Late edit to change "favor the occurance" to "favor the fixation" - a question of clarity. Sorry. [This message has been edited by Quetzal, 01-22-2003]
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Peter Member (Idle past 1509 days) Posts: 2161 From: Cambridgeshire, UK. Joined: |
quote: ... the reason I brought this up is that, if there is somesuspicion over the validity of the 'mitochondrial clock' then your argument here is non-existent. You are saying that with a 1 in 300-600 gen. mutation ratewe couldn't see what we see without NRM's, but that that assumed rate is incorrect and in reality much faster. In which case we could explain what we observe (if we can divergefrom chimps in 150ky then the minor divergences amongst humans is easy to accomodate). Taking assumptions from different models is a fairly easy way tomake something look impossible.
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