Molecular Clockwork And Related Theories-Testing the basis for “Mitochondrial Eve.”

From: Janice Matchett <>
Date: Sun Feb 26 2006 - 21:59:54 EST

In line with recent discussion. ~ Janice

Molecular Clockwork And Related Theories
Athena Review ^

Posted on 02/25/2006 5:40:40 PM EST by
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Testing the basis for “Mitochondrial Eve.”

Molecular clocks, a complex topic central to
current debates on human evolution, first came
into prominence in paleoanthropology in the
1960’s. One well-known study by Vincent Sarich
and Alan Wilson of the University of California
(1967) measured the immunological reactions in
primates and other animals to a control sample of
the blood protein serum albumin. The differences,
assumed due to a constant rate of evolution
through mutations, were then plotted on a linear
scale showing time elapsed since each species diverged from a common ancestor.

On the same principle, DNA, the genetic
reproductive molecule, is often used for
inter-species comparison. Assuming a constant
rate of mutation or random replacement of
amino-acid codes in DNA, the time elapsed between
descent from a common ancestor can be calculated
by comparing DNA segments from many different
animal populations, from sharks to chimpanzees.
With access to a large genetic data base and a
computer program for “best fit” distance trees,
evolutionary histories or phylogenies can be
constructed independently of the often problematic, gap-filled fossil record.

Increasingly, evolutionary biologists have
employed the relatively simple genetic makeup of
mitochondrial DNA (mtDNA) as an efficient form of
molecular clock. Mitochondria, energy-producing
organelles in cells, have their own DNA strands
which, limited in function to mitochondrial
reproduction, are significantly shorter than
those in the nucleus of a cell. Mutations in the
simpler mitochondrial DNA occur much faster than
in nuclear DNA, compressing more evolutionary
generations into less time. Adding to the appeal
of mtDNA for tracking evolutionary history has
been the wide consensus that, after conception,
only the egg’s mitochondria survive, and mtDNA is
therefore inherited only through the maternal line.

During the past 15 years, extensive searches have
been made through genetic records to find a
“Mitochondrial Eve” of all modern humans. A
widely-publicized 1987 study by Cann, Stoneking,
and Wilson (the latter, also an author of the
1967 serum albumin study) used mtDNA comparisons
of 147 people from Europe, Africa, Asia,
Australia, and new Guinea to show all present
human mtDNA is descended from a single African
woman of about 200,000 years ago.

This has caused considerable controversy over
issues beginning with the chancy workings of
population genetics. Famines and other
catastrophic events about 200,000 years ago could
have caused genetic bottlenecks or constrictions,
eliminating older human ancestral lines. Today’s
retrospective survey of mtDNA would then show
only surviving types, misleadingly suggesting the
human species evolved at that later time (Weiss
and Mann 1990). Also involved is the independent
nature of mtDNA itself, evolving distinctly in
each individual from the nuclear DNA which is the criteria of speciation.
Comparisons based on nuclear DNA, for example,
reveal chimps and humans to be closer than does
mtDNA, which shows more similarities between
chimps and gorillas. Finally, recent evidence
(discussed below) suggests the assumption that
mtDNA is only passed through the female line may itself be faulty.

The Mitochondrial Eve theory also seems to many
researchers to be at variance with the fossil
record, which shows widespread hominid migrations
and variation after 2 million years ago (myr),
well documented for Homo erectus in China, Java,
and the Black Sea by 1.8-1.6 myr, and Archaic
Homo sapiens and Neanderthals after 0.6 myr.
According to the Mitochondrial Eve theory, all
non-African H. erectus and H. neanderthalensis
populations are unrelated to the evolution of
anatomically modern humans (H. s. sapiens). This
directly contradicts the “Regional Continuity”
model used by many paleoanthropologists. In spite
of such controversies, the Mitochondrial Eve
theory has considerable scientific adherence and
popular recognition. A new study by South African
researchers, for example, proposes the most
ancient mtDNA belongs to “Bushwomen” or Khoisan
people. Recent genetic studies in China,
meanwhile, lend support to “out of Africa” theories.

As masses of data accumulate from the
statistically-oriented studies of mitochondrial
biology, it is becoming apparent that the
required methodology of studying mtDNA is
anything but straightforward. Currently under
fire is the once-canonical view that mtDNA is
inherited only through the mother, now challenged
by a set of studies reported in Proceedings of
the Royal Society (7 March 1999) by Erika
Hagelberg of Cambridge University, and Adam
Eyre-Walker, Noel Smith and John Maynard Smith of
Sussex University. It has long been known that
paternal mitochondria can sometimes penetrate the
human egg and survive for several hours. While
studies of mice and other organisms have actually
shown recombination between male and female
mtDNA, evidence of mtDNA recombination in human
populations has been very elusive.

Now such evidence appears to have been found in a
mtDNA research project led by Erika Hagelberg on
the tiny island of Nguna, in the archipelago of
Vanuatu in Melanesia (west of Polynesia including
the Solomon Islands and Fiji). Studying human
migrations, Hagelberg and her colleagues were
analyzing hundreds of people from Papua-New
Guinea and Melanesia. MtDNA samples on Nguna
Island showed, as expected, three main population
groups from colonizations over thousands of
years. But in all three there also occurred a
single mutation previously only known from one
northern European. Hagenberg and her colleagues
(1999) think it highly improbable for such a rare
mutation event to occur repeatedly in such an
isolated location. A more likely explanation
would be recombination between different mitochondrial DNA types.

Similar conclusions were drawn by Adam
Eyre-Walker and his colleagues at Sussex
University, from statistical analysis of
“homeoplasies,” common mutations in mitochondrial
proteins that occur in seemingly distinct
lineages around the world. Assuming maternal
inheritance only of mtDNA, these were thought to
be “hypervariable” sites where mutations occurred
with high frequency. Review of some European and
African mtDNA sequences by Eyre-Walker et al.,
however, show no evidence that these sites are
particularly variable over all lineages. Most of
these mutations were found in only a limited
geographic area, suggesting they occurred rarely
and then spread locally by recombination, which
appears a far more likely cause of the homeoplasies.

Such findings, if upheld, seriously complicate
the basis of using mtDNA to provide
straightforward genetic lines, such as assumed in
the Mitochondrial Eve hypothesis. The surprising
homogeneity in the mtDNA of modern humans
interpreted, in the Mitochondrial Eve hypothesis,
as resulting from a recent common ancestor, may
simply show the dilution of mutations caused by the recombination of mtDNA.

Even occasional mixing of maternal and paternal
genes would make it uncertain whether new traits
in two different human lineages are due to two
independent mutations or to the transfer of a
mutation from one lineage to another by
recombination. Recombinations could also add to
or erase changes from mutations, thus blurring,
as Hagelberg's team points out, the differences
between mtDNA lineages. This would make any past
evaluations of human history using mtDNA,
including the Mitochondrial Eve theory, subject
to cautious reinterpretation. This most directly
impacts the time scale of Mitochondrial Eve, and
seriously weakens the value mtDNA mutation rates
as a molecular clock. Recombination with paternal
mtDNA causing some variation in mtDNA would make
its mutation rate much lower than biologists
thought. Eyre-Walker notes Eve may have lived
twice as long ago as current estimates.

The controversial recombination factor is
providing new directions for research and
interpretation. In 1997, Svante Pääbo of the Max
Planck Institute of Evolutionary Anthropology in
Leipzig retrieved Neanderthal DNA over 50,000
years old, which he determined to have not
contributed in any way to the mtDNA of modern
humans. But the possibility of recombination
suggests to Erika Hagelberg that Neanderthals
might be more closely related to modern humans
than Pääbo’s mtDNA data shows. Pääbo partially
agrees, but feels recombination has not yet been
effectively proven. MtDNA shows Neanderthals
equally distant from both modern Europeans, whom
they may be ancestral to, and unrelated populations.

Further research on mtDNA evolution should serve
to identify and eliminate the specific genes
which mutate at abnormally fast or slow rates.
Jody Hey and Eugene Harris of Rutgers University
suggest that future work should increasingly
concentrate on the more complex nuclear genes. A
recent study by Hey and Harris (1999) on the
mutation rate of PDHA1 genes in the X Chromosome,
thought to have a steady rate of mutation, has
identified two populations at least 200,000 years
old ancestral to modern humans. To determine the
mutation rate of the gene, these were compared to
the differences between human and chimpanzee
PDHA1 genes, diverging at least 5-6 million years
ago. They found that prior to 200,000 years ago,
one form of this gene existed only in Africa and
led to types only in modern Africans. Another
existed only outside of Africa with one variant
found in some modern Africans and another which
split ca. 200,000 years ago into two haplotypes found in non-Africans.

Milford Wolpoff of the University of Michigan, a
long-time opponent of the oversimplified use of
molecular clocks (1988), supports the recent
findings of Hey and Harris. If this evidence is
not to make “Out-of-Africa II” theories obsolete,
they may nevertheless need to evolve
significantly themselves, to accommodate Asian
and European populations originating in Africa
but leaving considerably earlier than 100,000 to 200,000 years ago.

[References: Cann, R.L., M. Stoneking and A.C.
Wilson, Nature 325, 1987; Eyre-Walker, A., N.H.
Smith, and J. Maynard Smith, Proc. Royal Society
B, 1999, Vol.266, pp.477-483. Hagelberg, E. et
al., Proc.Royal Society B, 1999 (vol 266, p.
485), Hey, J. and E. Harris, Proc. Natl. Academy
of Sciences, 16 Mar. 1999; Ji et al., Nature 398,
1999; Kumar, S. and S.B. Hedges, Nature 392,1998;
Merriweather, D.A. and F.A. Kaestle, Science 285,
1999; Sarich, V.M. and A.C. Wilson, Proc. Natl.
Academy of Sciences 58, 1967; Weiss, M.L. and
A.E. Mann, 1990, Human Biology and Behavior,
Scott, Foresman; Wolpoff, M.H., et al, Science 241, 1988]
Received on Sun Feb 26 22:00:53 2006

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