non-conservative changes in amino acid sequences

John Clement clement at mail.utexas.edu
Thu Oct 2 13:09:44 EST 1997


I was wondering if there are methods available for determining if there 
are branches on an evolutionary tree where amino acid sequences have 
undergone signficant amounts of non-conservative change in their 
side-chain chemistry.

I would also like to know if my own naive method is valid.  PROTDIST in 
PHYLIP allows distance estimation based on Felsenstein's CATEGORIES 
model.  This model allows you to set a parameter such that changes among 
chemical classes of amino acids are either highly unlikely (as the value 
approaches zero) or are not treated differently from conservative 
changes (when the value = 1.0).  It seems to me that if you estimated 
the distances for a set of sequences using both extremes of this 
parameter, and fit those distances to a tree, branches on which a 
considerable amount of non-conservative change had occurred would have a 
much higher length under, say, value=0.1 than under value=1.0, relative 
to other branches of the tree.

In other words, if you have three branches of a tree, a, b, and c, 
estimate the distances using both values, and fit them to the tree.  If 
l(a,0.1)/l(a,1.0) is much greater than l(b,0.1)/l(b,1.0) and 
l(c,0.1)/l(c,1.0), then that is evidence for a greater amount of 
non-conservative change on a than on b and c.  Or perhaps one could 
weight the branch lengths by the proportion of change each represent in 
the tree.  I. e., instead of l(a,0.1), use

l(a,0.1)/(l(a,0.1)+l(b,0.1)+l(c,0.1))

and so forth.  Is this a legitimate approach?


John Clement
Botany Department
University of Texas
Austin, TX  78713
clement at mail.utexas.edu




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