RATES OF TRANSITION AND TRANSVERSION IN CODING SEQUENCES SINCE THE HUMAN-RODENT DIVERGENCE

Protein-coding sequences of 337 human genes were compared with those o f homologous genes from rodent (mouse or rat). A composite alignment c ontaining 477,189 nucleotide positions was constructed, and 21,570 ami no acid replacements were inferred. The rates of transitional and tran sversional silent substitutions in fourfold degenerate sites are estim ated as 1.71 X 10(-9) and 1.22 X 10(-9) site(-1) year(-1), respectivel y. Rates of substitutions in replacement sites, subject to selective c onstraints mediated by the genetic code, are lower, but also reflect a transitional bias. The amino acid exchange rejected least often durin g evolution is Asp/Glu, which is fixed at 30% the rate of transversion s in silent sites. The most mutable amino acids in this survey are thr eonine and serine; serine coded by AGY is more mutable than serine cod ed by TCN. A scoring matrix for evaluating amino acid similarity was d erived from this study. (C) 1994 Academic Press, Inc.