Synonymous nucleotide substitution rates in mammalian genes: implications for the molecular clock and the relationship of mammalian orders.

Synonymous substitution rates have been estimated for 58 genes compared among primates, artiodactyls, and rodents. Although silent sites might be expected to be neutral, there is substantial rate variation among genes within each lineage. Some of the rate variation is associated with G + C content: genes with intermediate G + C values have the highest rates. Nevertheless, considerable heterogeneity remains after correcting for G + C content. Synonymous substitution rates also vary among lineages, but the relative rates of genes are well conserved in different lineages. Certain genes have also been sequenced in a fourth order (lagomorph or carnivore), and these data have been used to investigate mammalian phylogeny. Data on lagomorphs are consistent with a star phylogeny, but there is evidence that carnivores and artiodactyls are sister groups. Genes sequenced in both rat and mouse suggest that the increased substitution rate in rodents has occurred since the rat/mouse divergence.