MAMMALIAN GENE EVOLUTION - NUCLEOTIDE-SEQUENCE DIVERGENCE BETWEEN MOUSE AND RAT

As a paradigm of mammalian gene evolution, the nature and extent of DN A sequence divergence between homologous protein-coding genes from mou se and rat have been investigated. The data set examined includes 363 genes totalling 411 kilobases, making this by far the largest comparis on conducted between a single pair of species. Mouse and rat genes are on average 93.4% identical in nucleotide sequence and 93.9% identical in amino acid sequence. Individual genes vary substantially in the ex tent of nonsynonymous nucleotide substitution, as expected from protei n evolution studies; here the variation is characterized. The extent o f synonymous (or silent) substitution also varies considerably among g enes, though the coefficient of variation is about four times smaller than for non-synonymous substitutions. A small number of genes mapped to the X-chromosome have a slower rate of molecular evolution than ave rage, as predicted if molecular evolution is ''male-driven.'' Base com position at silent sites varies from 33% to 95% G + C in different gen es; mouse and rat homologues differ on average by only 1.7% in silent- site G + C, but it is shown that this is not necessarily due to any se lective constraint on their base composition. Synonymous substitution rates and silent site base composition appear to be related (genes at intermediate G + C have on average higher rates), but the relationship is not as strong as in our earlier analyses. Rates of synonymous and nonsynonymous substitution are correlated, apparently because of an ex cess of substitutions involving adjacent pairs of nucleotides. Several factors suggest that synonymous codon usage in rodent genes is not su bject to selection.