AMINO-ACID SUBSTITUTION DURING FUNCTIONALLY CONSTRAINED DIVERGENT EVOLUTION OF PROTEIN SEQUENCES

In aligning homologous protein sequences, it is generally assumed that amino acid substitutions subsequent in time occur independently of am ino acid substitutions previous in time, i.e. that patterns of mutatio n are similar at low and high sequence divergence. This assumption is examined here and shown to be incorrect in an interesting way. Separat e mutation matrices were constructed for aligned protein sequence pair s at divergences ranging from 5 to 100 PAM units (point accepted mutat ions per 100 aligned positions). From these, the corresponding log-odd s (Dayhoff) matrices, normalized to 250 PAM units, were constructed. T he matrices show that the genetic code influences accepted point mutat ions strongly at early stages of divergence, while the chemical proper ties of the side chains dominate at more advanced stages.