sequence comparisons of paralogus gene families

Bruce J. Turner fishgen at vt.edu
Tue Jul 1 13:39:52 EST 1997


I am studying the mhc1 genes of a homozygous, clonal vertebrate and have
come upon a challenging situation which I would like to share. The
hypothesis is that there is divergence among clones in the some of the
exons of these genes, and that this divergence is mediated by natural
selection.  These genes occur as a small paralogous family, probably with 5
- 10 members per genome.  The exons of the paralogs within a given clonal
genome tend to be quite divergent and rich in nonsynonymous substitutions;
intron sequences are as yet uncharacterized.  Since the paralogs are
already known to be divergent via nonsynonymous substitutions, critical
testing of the hypothesis requires interclonal comparisons be made among
orthologous genes only.  This turns out to be not straightforward, for,
even if intron sequences were available, it is not clear that they would be
divergent enough in characteristic features to enable me to neatly and
completely resolve the mhc genes in two or more genomes into orthologous
categories.  In talking with people here who are more experienced with the
techniques of sequence comparisons, I'm getting the message that the
problem I'm posing is really "pushing the envelope" conceptually and
practically.

Is anyone out there aware of attempts to deal with similar questions?  If
so, what methods were used?.  I'm thinking of using maximum parsimony on
the intron sequences exclusively, and constraining the output such that
only interclonal comparisons are allowed.  Intron sequences from two
different genomes which cluster immediately will be considered to be
"orthologous", and their corresponding exons will be compared for the
purposes of testing the hypothesis.  Does this seem reasonable?  Are there
better ways?   Thanks for your help...



******************************************************************
Bruce J. Turner
Dept. Biology
VPISU ("Va Tech")
Blacksburg, VA 24061-0406
(540)-231-7444 (V)
(540)-231-9307 (F)
fishgen at vt.edu
webpage:  http://art.biol.vt.edu/Facultypages/Turner/Turner2.html
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