Dear list members,
Greg Billock's cogent post regarding molecular clocks is time well =
spent.=20
In contrast to the long held agreement that the rate of point =
mutations is uniform over the entire genome of an organism and that, =
therefore, nucleotide substitution rate variations among DNA regions =
reflected differential selective constraints, Wolfe, Sharpe and Li =
(Wolfe K.H., Sharp P.M., Li W.H. (1989) Mutation rates differ among =
regions of the mammalian genome. Nature 337(6204):283-285) argued that =
evidence for variations in mutation rates among regions of the mammalian =
genome were due to the differences in the timing of chromosomal =
replication within germline cells. Their observation also provide a =
mechanism to explain why some selectively neutral silent nucleotide =
substitution sites do not appear to "tick" to the same molecular clock.=20
=09
Fitch (Fitch, W.M. (1994) Molecular Clocks Are Better Than You Think. =
Journal of General Physiology 102(6):1a. ) contends that the seeming =
manege of molecular clocks can be navigated by throwing out the "false =
assumption" that there is an equal potential for change in all amino =
acid positions. Fitch argues that for any given lineage, at any point =
in it's evolutionary history (i.e., time) the numbers of amino acid =
positions subject to replacement is only a fraction of the total. As a =
consequence the probability of same-site multiple replacements is =
greater. Further, there is a "saturation phenomenon" that accounts for =
decreased relative changes as divergence time increases.
In a strong affirmation of the underlying postulate of constraint, =
Fitch claimed that data can be "consonant with a perfect clock provided =
only that we specify the number of concomitantly variable codons =
(covarions) and the rate at which the pool of covarions turns over."
There is also a rational argument to be made regarding the plausibility =
that selection is simply weaker at the at the molecular level and that, =
while selection can operate at the molecular level -- the mechanisms of =
mutation and drift predominate.
It is worthwhile to note that phenotypic changes may be due more to =
differences in gene regulation than in sequence alterations. In =
addition, many researchers who do not agree with the arguments offered =
by the molecular clock hypothesis await a deeper understanding of =
relationship between biochemical evolution and genetic differentiation =
before being able to evaluate the accuracy, reliability, and =
applicability of such clocks.=20
These reservation are, however, a long way from the misguided criticism =
of molecular clocks put forth by Denton and Behe and very far from =
being worrying to evolutionary theory.
I'll re-read the Science article titled, "Calibrating the Mitochondrial =
Clock". However, at first blush, I'm at loss to see any new criticism of =
the practical applications of molecular clock theory.
In truth the molecular clock hypothesis is tied to a troubled neutral =
theory and it is important to remember that, whenever a technique or =
hypothesis becomes detached from its theoretical underpinnings -- and =
becomes instead girded by ad hoc explanations and situational laws -- =
one would be well remanded to Tacitus: For if it is true that "the =
more corrupt the republic, the more laws multiply" -- perhaps it is =
likewise true that the more corrupt the scientific hypothesis, the more =
"explanatory mechanisms" multiply.
Best Regards,
K. Lee Lerner
Science Policy Institute
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