Humans slow mutation rate (Science)

Grier Page gpage at gsbs.gs.uth.tmc.edu
Mon Apr 24 14:27:30 EST 1995

In article <Pine.3.05.9504170839.A7488-b100000 at mcz>, dmw at MCZ.HARVARD.EDU (Daniel Weinreich) says:
>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
>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. 

	This question is being addressed in a series of papers form Dr. W-H Li's lab. 
They are look at the rates of evoution of the introns, all the better to reduce selective pressure,
of genes on the X, Y and autosomal chromsomes. These genes include Zf-x znd Zf-y.
What they have found is that the genes on the Y chromsome are evoluting at the fastest rate.

>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.

	This is not the result of what enzymatic differences but due to difference in the
number of divisions a egg goes through verses a sperm. Once a female is born she her eggs
hav gone through all divisions that they will go through except  that of Meisosis II. This is different from
males who has a certain number of primodial germ cells that divide and a vertain sub set become sperm but some will continue to divide and
product more 'daughter' cells for many years and divisions to come.  Thus at birth the male and female cells gametes have 
undergone a similar number of replications, but as a male gets older the sperm cells have gone through more divsions.
	This pre-supposes that most mutations are primarily the result of replication errors and not of time.
	Thus the work in Dr. Li's lab is looking to see if the rates of evolution of genes on the Y are evolving faster than
the X or autosomes. The idea is based upon some work by an author who escapes me but he said that teh Y is only in males,
the X and teh Autosome in both males and females. but each 'X' spends 2/3 of its time in females what and autosome spends 
1/2 of its time in females. Thus by looking at the rates of evolution of homologous genes across species and chromsomes
one can make an inference about wether time or replications are the prime driving force of evolution.
	The papers seems to indicate that replications are the prime source of mutationa nd changes and
thus the prime driving force for evolution. This gives rise to what is called 'male drive evolution'.

	As far as the molecular clock goes...
	I believe that as generation time increases the number of repliction per year drops. Thus if one builds one the
premise that replications and not time drive molecular change then it is logical for species with longer lifespans 
to have a slower, apparent,  molecular clock.

	I think most of the refences to Dr. Li's papers are in the Science article.

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