Re: New Cytochrome C evidence

On Sun, 10 Aug 2008 11:42:29 -0700 (PDT), Ron O <rokimoto@xxxxxxx>
wrote:

On Aug 10, 9:46 am, r norman <r_s_norman@xxxxxxxxxxxx> wrote:
On Sun, 10 Aug 2008 06:44:43 -0700 (PDT), Ron O <rokim...@xxxxxxx>
wrote:





On Aug 9, 3:14 pm, r norman <r_s_norman@xxxxxxxxxxxx> wrote:
On Sat, 9 Aug 2008 12:07:04 -0700 (PDT), _Arthur

<Arth...@xxxxxxxxxxxx> wrote:
Complete Neanderthal Mitochondrial Genome Sequenced From 38,000-year-
old Bone
http://www.sciencedaily.com/releases/2008/08/080807130824.htm

"Analysis of the new sequence confirms that the mitochondria of
Neanderthals falls outside the variation found in humans today,
offering no evidence of admixture between the two lineages although it
remains a possibility. It also shows that the last common ancestor of
Neanderthals and humans lived about 660,000 years ago, give or take
140,000 years.

Of the 13 proteins encoded in the mitochondrial DNA, they found that
one, known as subunit 2 of cytochrome c oxidase of the mitochondrial
electron transport chain or COX2, had experienced a surprising number
of amino acid substitutions in humans since the separation from
Neanderthals. While the finding is intriguing, Green said, it's not
yet clear what it means."

-------------------

Let's see how Sean Pitman spins this one.  Of course, no "1000 aa"
changes were involved, so it falls under the Pitman Treshold.

The paper is

A Complete Neandertal Mitochondrial Genome Sequence
   Determined by High-Throughput Sequencing
Richard E Green (and 24 co-authors)
Cell 134(3): 416-426( 8 August 2008)

"A complete mitochondrial (mt) genome sequence was reconstructed from
a 38,000 year-old Neandertal individual with 8341 mtDNA sequences
identified among 4.8 Gb of DNA generated from 0.3 g of bone. Analysis
of the assembled sequence unequivocally establishes that the
Neandertal mtDNA falls outside the variation of extant human mtDNAs,
and allows an estimate of the divergence date between the two mtDNA
lineages of 660,000 ± 140,000 years. Of the 13 proteins encoded in the
mtDNA, subunit 2 of cytochrome c oxidase of the mitochondrial electron
transport chain has experienced the largest number of amino acid
substitutions in human ancestors since the separation from
Neandertals. There is evidence that purifying selection in the
Neandertal mtDNA was reduced compared with other primate lineages,
suggesting that the effective population size of Neandertals was
small."

The "surprising number of amino acid substitutions" is four.  I don't
think Pitman will be too impressed.  As to the significance of these
four changes, the authors state: "However, all these substitutions are
in regions of the protein that, based on the crystal structure, do not
have any obvious function, and they are variable among primates.
Hence, they may represent either minor adaptive advantages, perhaps of
regulatory relevance, or have no significant functional consequences
for mitochondrial function."-

I recall that other researchers in the past have pointed out that
humans and their close relatives seem to have a rapidly evolving COXII
gene compared to other mammals.  One explanation is that we inherited
a defective COXII system from our monkey like ancestor.  Either a
mutation in the COXII gene or another protein that COXII interacts
with cause a portion of the COXII gene to become more selectively
neutral (lost function).  Either the higher number of substitutions
don't matter any more or they are selected for because they might be
"fixing" the problem or at least making the situation a little
better.  Either way we might have inherited some defect that we and
our ancestors have had to live with for millions of years, but most
other species have no such problem.

Based on the chimp and gorilla sequence did the substitutions occur in
the human lineage or Neandertal lineage?

In the human line, if I recall correctly.

Maybe we got lucky with one of the substitutions.

We spend a lot of calories on maintaining our brains. If there is an
inefficiency in our oxidative phosphorylation chain it would be a big
deal.

It is sort of counter intuitive that the primate lineage may have
selected for larger brains to run a race to collect enough calories to
survive.

If primates are less efficient at producing ATP oxidatively they would
have to evolve a way to insure that they could collect more calories
than their competition. You have to wonder if larger brains be would
be a hindrance or a positive?


That is a far too simplistic look on cytochrome oxidase mutations.
Total failure of the cytochrome system is devastating, but the effects
are usually not to block the activity but to cause subtle
modifications of it. Known allelic variations usually cause moderate
to severe deficiencies in visual or muscular systems. However neutral
variation only mild defects will go undiscovered because of lack of
interest in chasing down changes that have no discernable effect.

See "Mitochondrial DNA sequence variation in human evolution and
disease", D. Wallace, PNAS 91:8739-8746(Sept. 1994).
http://www.pnas.org/content/91/19/8739.full.pdf

"Germ-line and somatic mtDNA mutations are hypothesized to act
together to shape our history and our health. Germ-line mtDNA
mutations, both ancient and recent, have been associated with a
variety of degenerative diseases. Mildly to moderately deleterious
germ-line mutations, like neutral polymorphisms, have become
established in the distant past through genetic drift but now may
predispose certain individuals to late-onset degenerative diseases. As
an example, a homoplasmic, Caucasian, tRNAGln mutation at nucleotide
pair (np) 4336 has been observed in 5% of Alzheimer disease and
Parkinson disease patients and may contribute to the multifactorial
etiology of these diseases. Moderately to severely deleterious
germ-line mutations, on the other hand, appear repeatedly but are
eliminated by selection. Hence, all extant mutations of this class are
recent and associated with more devastating diseases of young adults
and children"



.

Relevant Pages

  • Re: New Cytochrome C evidence
    ... Neanderthals and humans lived about 660,000 years ago, give or take ... Neandertal mtDNA falls outside the variation of extant human mtDNAs, ... That is a far too simplistic look on cytochrome oxidase mutations. ...
    (talk.origins)
  • Re: New Cytochrome C evidence
    ... Neanderthals and humans lived about 660,000 years ago, give or take ... Neandertal mtDNA falls outside the variation of extant human mtDNAs, ... That is a far too simplistic look on cytochrome oxidase mutations. ...
    (talk.origins)
  • Re: New Cytochrome C evidence
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    (talk.origins)
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