molecular clocks

Steven Smith smith at plasma.harvard.edu
Sat Sep 7 22:35:22 EST 1991


tomh at BAMBI.CCS.FAU.EDU (Tom Holroyd) writes:

>I still wonder about totally neutral mutations.  What would be an example?
>How do we know a large proportion of bases are silent?

Tom,
  Have you taken a look at any real data?  There are numerous examples
available in the databases (Genbank etc.) of genes that differ considerable
at the nucleic acid level, yet still produce identical amino acid sequences.

  When discussing the issue of clocks you must make two distinctions. First
there is a difference between changes in the genotype and changes in the
phenotype.  The clock/constant rate arguement can only be discussed reasonably
on the genotype, as that is the only place that one can quantitatively measure
change.  There are organisms on the planet that have demonstrated little change
in their phenotype for millions of years.  But this is not to say that they
have not suffered numerous mutations at the DNA level.  These so called 
"living fossils" such as the crocodile, the selocant (surely misspelled),
and in fact many anaerobic bacteria can be demonstrated (by phylogenetic
analysis such as parsimony analysis) to be as distant from the protogenote
as any of their more contemporary counterparts.  This implies that even
phenotypically "stable" organisms still fall prey to random mutations.

  The second issue is that the clock for different genes and gene families
is different.  That is because the evolutionary pressures on different
genes are different.  This doesn't mean that the average rate of random
mutations differs for these genes.  It only means that different genes
respond to these mutations in a different way.  So trying to use a "clock"
to measure the date of divergence between two species one must understand
the mutation behavior of the gene in question.  This is accomplished by
means of comparative analysis on a large number of representitives genes
from many different organisms.

  The fact that clocks differ from gene to gene does not make the agruement
for a clock invalid.  It can be a useful tool in trying to place dates
of divergence of genes as well as whole organisms.

Sincerely,

Steven Smith
Harvard Genome Lab
smith at nucleus.harvard.edu
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