Re: Online archy courses

From: Philip Deitiker (Donevenask_at_worlnet.att.net)
Date: 12/23/04

  • Next message: Philip Deitiker: "Re: MV is the most published author of SAP"
    Date: Thu, 23 Dec 2004 03:15:12 GMT
    
    

    G Horvat <g-horvat@shaw.ca> says in
    news:smfjs05pk67tdhlbbe2asijs4agds51ver@4ax.com:

    > On 22 Dec 2004 15:39:29 GMT, Philip Deitiker
    > <Nopdeitik@att.net.Spam> wrote:
    >>>... how is it known that exo-African homo erectus did not
    >>> have mtDNA sequences which were closer to those of
    >>> exo-African homo sapiens than to sub-saharan homo sapiens?...
    >
    >>Same reason for Neandertals. Erectoids migrated out of africa
    >>[or evolved out of africa] 1.6 million years ago. While you
    >>may disagree that Paabo and companies estimates of mtDNA
    >>coalescence are late, you cannot propose that mine are because
    >>I included also in those estimates the issues of recurrent
    >>mutations and its effect on estimating the MRCA. When this was
    >>done the earliest possible MRCA for humans is around 320 years
    >>for mtDNA. ...
    >
    > If mutations accumulated in a clock-like manner, then it should
    > be possible to determine fairly accurate times of coalescence
    > but I don't think that they did and so both your's and Paabo's
    > estimates mean nothing to me (to be perfectly frank).
    >
    > With regards to this subject, Ingman et al. (2000) wrote:
    >
    > "The molecular clock hypothesis postulates that DNA sequence
    > evolution is roughly constant over time in all evolutionary
    > lineages. We used a test that compares the log likelihoods of
    > trees reconstructed with and without the molecular clock
    > assumption to examine the supposition that the mtDNA lineages
    > evolve at `clock-like' rates. The human mtDNA sequences,
    > excluding the D-loop, have evolved at roughly constant rates (P
    > = 0:094) ..."

    Evolution did not speed up because for neandertals. Do you see any
    reason to suggest evolution of european mtDNA is faster than african
    mtDNA by a 10 fold rate? If not why would you propose that Neandertal
    a. went backwards in the direction of chimpanzee, b. sped up by ten
    fold.
     
    > So, as you mentioned in an earlier posting, they considered the
    > regions in which the Neandertal sequences were obtained
    > unsuitable for dating but thought the coding region portions
    > were better. In a later study, Herrnstadt et al. (2002), were
    > less optimistic:
    >
    > "The results presented here indicate that further investigation
    > of these key evolutionary processes is necessary and that
    > advocacy of such haplogroup-dating schemes should be tempered
    > with caution. In an important analysis, Torroni et al. (2001b)
    > have obtained evidence that there is not an mtDNA "clock" (i.e.,
    > a constant, single rate of DNA evolution) and have provided
    > preliminary evidence that different subclusters within the same
    > haplogroup have evolved at different rates. Those results will
    > undoubtedly catalyze further investigations."

    But I explained why that is and I provided a confidence interval for
    those reasons. The reason is more or less of a technical nature.
    There is too much time to use transitions as a proper means of
    estimation because of the issue of homoplasies, none the less
    estimates using transitions and adjusting place the branch prior to
    the radiation of humans, prior to the human MRCA. The level of
    transversions are too few to statistically predict that date, however
    nonetheless the 3 transitions and 1 deletion between humans and
    neandertals place that distance as being >1 million years.

    So basically for your argument to be true.
      The HVR transition rate would have to had spead up for unknown
    reason and no homoplasies.
      The HVR transition rate would have to had spead up for unknown
    reason.
      The average distance between the deepest branches of humans in HVR
    is 13 mutations at lHVR1 which can be rooted at the center of this
    divergence with chimpanzee sequence. The average number of
    transversions between the deepest branches is 0.6
      
      The basic problem is a relative one. Neandertal human temporal
    distance is such it falls in a grey area between two estimation
    techniques. The only logical reason that it can fall into that range
    is simple, it is too old for one technique and too young for another,
    therefore it has to be outside the effective range for clocking that
    we apply to humans, and too young to be effectively clocked as we did
    for C/H divergence. Meaning that the split between Neandertals and
    Human logically has to be between human MRCA and C/H MRCA. In fact
    the human clocking parsimony places it certainly well before our
    MRCA, but uncertainly relative to 2 or 5 fold times that MRCA.

      Anybody can make any excuse they want and confuscate the issue. But
    the reality is that there exist a human tree of more or less
    parsimonious nature with regard to mtDNA. The deepest branches are in
    africa, something you will agree with. When Neandertal sequence is
    placed in that framework it taps the basal branch and when chimpanzee
    is added as an outgroup that 'tap' joins the chimpanzee outgroup
    ancestral to human and to neandertal creating a relatively balanced
    split. Everyone author admits this, even though some confuscate the
    issue.

      You can ignore this evidence if you like, but it will not change
    the nature of the evidence. I should point out that Ingman/Paabo
    style averaging which takes a really good method, pairwise comparison
    and then extends it beyond its use has resulted in misstatments.
    Notably his own colleage found that the Andaman's likely left africa
    prior to his suggested 53 kya. The same mistake is made by other
    authors with regard to Neandertal.
      Averaging only works real well if the population has expanded in a
    more or less circular symmetrical manner. The branching between
    neandertals and humans shows neither a human based expansion
    similarity or symmetry. The branch legs in Neandertal are
    considerably longer than the human average, about 3 times longer, and
    they show no branching as is seen with all human haplotypes, except
    at the end points. Therefore these average comparisons are not useful
    and one MUST look for a parsimonious explanation. That explanation is
    clear. To be frank if you don't understand that then you need to read
    more about how evolution works.
      With regard to Paabo and Ingman, There assumption is that if the
    various branches are approximately the same age, then they must
    represent a single migration. The flaw in that logic is that the
    variation of parameters means that the relative exit times of a
    branch are +/-15% relative to the age, So that exit times of 30%
    difference 'really' show up as being insignificantly different in
    their analysis. Their analysis fails to consider the complexity of
    human migration and they do so with 50 exoafrican sequences. This
    does not improve on the information gained at HVR1, however it offers
    the potential with good even sample to gain better information. Have
    we seen that yet though, not in my opinion.
      There analysis of the coding region was unable to establish
    correctly when, where humans left africa. In the end there
    conclusions are not better than HVR1 comparisons. And, they do not
    have genomic comparisons of any neandertals and less a handful of
    chimpanzees.
      And BTW, where would we most likely to see branch length
    differences that could be used as a precedence? In chimpanzee and
    gorilla. Who looked at this carefully, me, who else? No one, not
    Paabo. What did I find, I found that branches of smaller populations,
    like bonobos had shorter branches. By how much? about 30% shorter.
    Have you looked at or compared any branching patterns in chimpazee?
    Have you looked at any branching patterns in gorilla? Has anyone
    looked at the branching patterns of genomic sequences in chimpanzee
    or gorilla before they wrote a paper establishing that genomics were
    far superior to use versus HVR1? No-one has done so, and especially
    not Paabo. So pretty much don't tell I don't know why I am setting a
    limit where I set it, until you have examined these issues yourself
    as thoroughly as I have done. And don't tell what Paabo thinks is
    exceptional, when he hasn't even laid the proper foundation for the
    basis of his work.
      How could a person possibly know what rate variation is if they
    have never looked beyond a population that radiated less than 160kya.
    Any variation you see for that population could simply be
    statistical. It requires the examination of deeply branching
    populations to see that clearly. And none of your 'heros' have done
    that, neither have you.
     
    > So, where are we right now?

    We are in a position to suggest that rate varies within a range, and
    that range is not 10 fold greater than our estimate. When we have
    uncovered sequences that have appeared to have varied greatly in
    humans, most are now considered to be errors. Therefore I stand
    behind my prediction of an outside limit of 320,000 for the human
    MRCA, unless someone can show me convincing data are reasoning to
    suggest that mutations occurred much slower than the very generous
    boundaries I have set, I see no reason to change that estimate. AND,
    no reasonable person would change that estimate to 1.6 million years
    without having a very, very good source of data that says so.
      What proof do you have specifically that the rate of mtDNA
    variation in any long lineage of humans L1, L2, L3 has on average
    varied by a 10 fold rate, 5 fold rate, 3 fold rate, 2 fold rate.
    You have no evidence that there is variance greater than about 1.5
    fold which could be explained by statistics. Even your vuanted author
    who claims a p=0.09 (Acceptable p for rejecting the null
    hypothesis is P<0.05) that rate is the variable by 10 fold.

    > Has anyone demonstrated that Ingman was wrong about the HV regions?

    Not wrong about HV, just not right about coding. HV does what it can
    do within the bounds of interpretation. HV did not get the major
    african lineages wrong, did it?

    > Has anyone determined that
    > Torroni was wrong about the absence of "a constant, single rate
    > of DNA evolution" in complete sequences?

    Duh, particularly in the coding because the coding region is under
    purifying selection, something I warned you about. The Coding is
    there to _Add_ information to HVR, the variable rate of genomic
    evolution is expected and has to be conditioned. When you get all
    those coding sequences done you going to run smack into Arnason all
    over again, 10 papers are going to flood the literature claiming that
    2/3rds of coding mutations are useless because they are to close to
    genes where purifying or region specific selection has taken place.
    mtDNA clocking is not wrong, its just imperfect, for statistical
    reasons, for precision reasons, for selective reasons. I have sided
    with you on the genomic issue for a technical point, as mtDNA
    branches approach the present there are too few mutations and
    branches, too much relative error for it to be useful. The assumption
    is that coding mutations will occur 4 to 5 times more frequent (per
    genome) than HVR. However I am fully aware that not all coding
    mutations will occur at the same rate, just as in HVR1.

    -- 
    Philip
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