Inferring Nonneutral Evolution from Human-Chimp-Mouse Orthologous Gene Trios

Even though human and chimpanzee gene sequences are nearly 99% identical, sequence comparisons can nevertheless be highly informative in identifying biologically important changes that have occurred since our ancestral lineages diverged. We analyzed alignments of 7645 chimpanzee gene sequences to their human and mouse orthologs. These three-species sequence alignments allowed us to identify genes undergoing natural selection along the human and chimp lineage by fitting models that include parameters specifying rates of synonymous and nonsynonymous nucleotide substitution. This evolutionary approach revealed an informative set of genes with significantly different patterns of substitution on the human lineage…