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Humans slow mutation rate (Science)

Daniel Weinreich dmw at MCZ.HARVARD.EDU
Mon Apr 17 08:39:21 EST 1995


On Fri, 14 Apr 1995, Brian Foley wrote:

> 	I have never understood why a short generation time would 
> increase the molecular clock, except that mutations are usually fixed at 
> germ cell division, so if human germ cells (eggs more so than sperm) 
> divide fewer times per 100 years than do mouse germ cells, this could 
> affect the rate.

IMHO this is the critical question: How many rounds of DNA replication per
generation are there in the germ line?  I'm ignorant and would love to
know the answer for some representative species in this debate; any
volunteers? 

Because it seems to me that unless one controls for this effect (and
possibly normalizes it to DNA replications per year), interspecies
comparisons of clock rates and discussions repair efficiency and
generation effects are incomplete.  Comments?  (I don't understand why the
previous writer distinguishes between egg and sperm cell lines.  Brian?)

> It would be interesting to see if genes on the Y chromosome which are
> always carried by [s]perm rather than egg, have a faster clock than
> genes on other chromosomes which are carried by both sperm and egg. 

I like this idea, and would predict that if the Y-clock runs faster it
must be the case than male germline cells undergo more rounds of DNA
replication/generation, since it seems unlikely (to me!) that the
enzymatic machinery differs in male & female germlines.  Though of course
I doubt we could all agree on what pair of loci would make a fair
comparison, since the principal "escapement" in the molecular clock is
purifying selection.

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Daniel M. Weinreich			email: dmw at mcz.harvard.edu
Harvard University 			usmail: 26 Oxford Street
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