Superfamily phylogenetics

Joe Felsenstein joe at genetics.washington.edu
Mon Apr 19 10:47:29 EST 1993

Michael McKenna posted a while ago raising the issue of whether
with members of a protein superfamily in which

> These sequences are very distantly related, if at
> all,

but in which

> Several of these molecules have 
> had their structures solved, and there is a compelling uniformity
> to their structure, even though the identity is very low at the
> primary level, often on the order of 20%.
> Is it possible to generate a phylogeny from
> sequence data when only dubious connections can be made with various 
> allignment algorithms. Most of the programs I have seen can do a 
> resonable job with clearly related molecules. I suspect it can't
> be done reasonably in this particular case. Any suggestions?

A number of people commented, to the effect that with poor alignment, 
it is very hard to make a phylogeny.

For now, that's correct, but it has often been noted that structures
are conserved even more than the amino acids from which they are made.
It will be possible in the future, with more algorithm development (which
partly waits for more structure data to play with) to infer phylogeny
from structure itself, amino acid sequence playing a secondary role.
There is at least one pioneering effort in this direction, a paper by
Johnson, Sali and Blundell in Methods in Enzymology volume 188, the volume on
molecular evolution.  They measured dissimilarity of structures and
based a distance method on the resulting measures, getting a reasonable

There are other ways too, and we can expect a lot more activity in this
area.  So perhaps we outght not be totally negative about the
possibilities here.

Joe Felsenstein, Dept. of Genetics, Univ. of Washington, Seattle, WA 98195
 Internet:         joe at genetics.washington.edu     (IP No.
 Bitnet/EARN:      felsenst at uwavm

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