ANALYSIS OF AMINO-ACID SUBSTITUTION DURING DIVERGENT EVOLUTION - THE 400 BY 400 DIPEPTIDE SUBSTITUTION MATRIX

Most formal methods for analyzing the divergent evolution of protein s equences assume a Markov model where position i in a polypeptide chain undergoes amino acid substitution independently from position i+1. Th e large number of aligned homologous sequence pairs available from the exhaustive matching of the protein sequence database makes it possibl e to examine this assumption empirically. We have constructed a 400 by 400 matrix that reports empirical probabilities for the interconversi on of all pairs of dipeptides in proteins undergoing divergent evoluti on. Comparison of these probabilities with those expected if substitut ion at adjacent positions in a protein sequence were independent revea ls interesting patterns that arise through the breakdown of this assum ption. Several of these are useful in extracting conformational inform ation from patterns of conservation and variation in homologous protei n sequences. (C) 1994 Academic Press, Inc.