definition of Orthologues, Homologues, etc

William R.Pearson wrp at alpha0.bioch.virginia.edu
Tue Oct 10 21:10:43 EST 2000


Mike Syvanen <syvanen at ucdavis.edu> writes:

> "William R. Pearson" wrote:
> 
> > Holger Hupfer <hupfer at botanik.biologie.uni-muenchen.de> writes:
> > > I am a little worried about the classifications of genes or proteins.
> > > What is the Difference between orthologues, homologues or analogues? Can
> > > anyone help me with this?
> >
> > Homologs refer to proteins that share a common ancestor.  Analogs (a
> > term that is rarely used), do not share a common ancestor, but have
> > some functional (rather than structural) similarity that causes them
> > to be included in a class (e.g. trypsin like serine proteinases and
> > subtilisin's are clearly not related - their structures out side the
> > active site are completely different, but they have virtually
> > geometrically identical active sites and thus are considered an
> > example of convergent evolution to analogs).
> 
> unless, of course, the active sites of trypsin and subtilisin are
> homologous and that they have subsequently fused to other
> nonhomologous proteins to produce today's members.

To argue that the active sites of trypsin and subtilisin are
homologous, is to argue for the inference of homology in the absence
of any objective evidence.  The active site of each protein is
comprised of three residues, which are spaced throughout the length of
each protein sequence.  There is no signficant sequence or structural
similarity shared by the two proteins; trypsin is comprised of two
beta-barrels while subtilisin is a largely alpha structure.

There seem to be two uses of the term "homology".  Some evolutionary
biologists extend the meaning of "common ancestry" well beyond what
can be tested experimentally, and may sometimes argue that all
proteins are ultimately homologous, based on the assumption that there
was a single primordial gene that, presumably through multiple
duplication events, gave rise to all current genes.

I prefer a definition of homology that is based on some objective
measure of similarity.  My ex-graduate student, Todd Wood, pointed out
to me that the original use of the work "homology" by Richard Owen,
first curator of the British Museum in the 19th century, was based on
morphological or developmental similarity.  From this perspective, all
genes (or proteins) cannot be homologous, because it makes no sense to
talk about the homology of dissimilar structures, e.g.  an all-beta
protein and an all-alpha protein. One might argue that they shared a
very ancient common ancestor, but it seems equally reasonable to
believe that both structures arose independently.  This perspective
demands evidence for homology; the null hypothesis is that almost all
genes are non-homologous.

The inference of homology, based on statistically significant sequence
or structural similarity, is an exceptionally powerful and reliable
tool for characterizing newly sequenced genomes.  The concept of
homology would be considerably less valuable if it could not be used
to infer structural similarity.

Bill Pearson








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