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Humans slow mutation rate (Science)

Brian Foley brianf at med.uvm.edu
Fri Apr 14 10:22:28 EST 1995

Giovanni Maga (maga at vetbio.unizh.ch) wrote:

: Dear colleagues,
: I found in Science issue 31st March 1995 pagg.1907-1908 an interesting
: report about Goodman's theory of slower mutation rate in humans. This idea,
: long time adversed, found new support by the data of Wen Li, presented in a
: Detroit symposium. He looked at non-coding sequences (pseudogenes, introns)
: of monkeys (New and Old World) and humans  by the relative rate test and
: found significantly slower mutation rate for humans. As a non-expert in
: evolution but as a molbiologist interested in DNA repair, I would welcome
: any comment about the hypothesis (already done by Britten, Science 231
: (1986), 1393-1398) that long-lived animals could have more efficient DNA
: repair systems than short-lived ones, which seems now to fit with this new
: data, but still surprising due to the highly conserved DNA repair
: mechanisms in eukaryotes. In general, I would also be interested to know if
: these results prompted already to revise the molecular clock model, as
: suggested in the article.
: Any comment is welcome.
: G.Maga, PhD
: maga at vetbio.unizh.ch

	I know there are several people who have published papers 
argueing that the "molecular clock rate" of different organisms varies as 
a function of reproductive time.  That animals such as rodents with a 1 
or 2 month period between generations have a faster molecular clock than 
do primates with generation times of 3 to 30 years.
	I could not find any references at my fingertips (no MedLine 
access from this computer) but I did a GOPHER search of the bionet 
newsgroups (URL = gopher://fly.bio.indiana.edu/) and came up with this:

---------- From bionet archives gopher -------------------
From: lamoran at gpu.utcc.utoronto.ca (L.A. Moran)
Subject: Mice and Molecular Clocks
Message-ID: <C2Eys6.2sD at gpu.utcc.utoronto.ca>
Organization: UTCC Public Access
Date: Sun, 14 Feb 1993 01:00:06 GMT
Lines: 62

I am responding to comments made in a posting from site rhoneycu at NSF.GOV. 
There was no signature so I don't know the name of the individual who
made the comments.

     "The problem with many molecular clocks for rodents is that 
      time effects are known to exist, especially for synonymous 
      substitutions. Thus, it is difficult to calibrate a clock based on 
      divergence rates of genes sequenced from other mammalian lineages.  
      In fact, the whole idea of calibrating clocks using some time of
      assumption that the same gene has a constant rate of change among 
      all mammalian lineages is wrong minded, and in fact, there is 
      empirical data to suggest otherwise."

I'm curious to know what you mean by "generation time effects". There are
those who argue that evoluton is faster in rodents than in some other mammals
because rodents have shorter generation times. I don't think that the data
for a rate differential is very good but even if it was it does not 
necessarily follow that generation times are the cause.

If one uses an appropriate outgroup then the rates of change in most 
lineages are similar for a number of genes. In other words all of the tips
of the branches of the dendrogram are equidistant from the root. This 
to me that there has been a (relatively) constant rate of change since the
time of the main mammalian radiation (about 100 myr). Why is this "wrong-

I agree with the rest of the article posted from rhoneycu at NSF.GOV where
he/she said that calibration points are necessary in order to calculate
absolute rates or divergent times. Where we differ, I suspect, is that
I believe that only a single calibration point (ie. mammalian radiation
at 100 myr) is necessary to provide an estimate of the rat/mouse divergence
because rates of change in all lineages are about equal. Thus if the
rat/mouse node is two thirds of the distance from the root then these
organisms likely shared a common ancestor 33 million years ago.

In that case the fossil record could be misleading or incomplete because
palaeontologists estimate about 15 million years. There are at least as 
many reasons why the fossil evidence could be incomplete as there are
criticisms concerning molecular data.

Let's look at a hypothetical example.

         |------------------------------------- whales     
         |                        |------------ mouse
                                  |------------ rat

        100                       15                       ages from
        myr                       myr                      fossil record

One interpretation of this data is that the 15 myr age must be incorrect
and the last common ancestor of mice and rats actually lived much earlier.
Another interpretation is that the 15 myr estimate is accurate and the 
rates of change in both mice and rats since the time of divergence have 
been much more rapid than in other lineages.

Laurence A. Moran (Larry)

--------------- end of post retrieved from IUBIO archives --------

	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.
        As far as I know humans have the longest generation time of 
primates, and thus may be expected to have a slower molecular clock.  It 
would be interesting to see 1) if genes on the Y chromosome which are 
always carried by perm rather than egg, have a faster clock than genes on 
other chromosomes which are carried by both sperm and egg.  2) if the 
molecular clock rate does vary with generation time in all cases, 
including elephants, whales, etc.  Or dies it have more to do with 
general metabolic rate than generation time?

*  Brian Foley               *     If we knew what we were doing   *
*  Molecular Genetics Dept.  *     it wouldn't be called research  *
*  University of Vermont     *                                     *

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