Molecular evolution of the COX7A gene family in primates.

COX VIIa is one of 10 nuclear-encoded subunits of the COX holoenzyme, and one of three that have isoforms with tissue-specific differences in expression. Analysis of nucleotide substitution rates revealed an accelerated rate of nonsynonymous substitutions relative to that of synonymous substitutions for the heart isoform gene (COX7AH) in six primate lineages. Rate accelerations have been noted for four other COX-related genes in this time period, suggesting that the COX holoenzyme has experienced an episode of adaptive evolution. A third member of the gene family, COX7AR, has recently been described. Although its function is currently unknown, low nonsynonymous substitution/synonymous substitution (N/S) ratios in mammalian evolution suggest that COX7AR is of functional importance. When the COX7A isoforms were divided into domains, examination of nucleotide substitution rates suggested that mitochondrial targeting residues experienced an accelerated nonsynonymous substitution rate in the period following gene duplication. In contrast, paralogous comparisons of the targeting residues of each isoform show they have been relatively conserved in mammalian evolution. This pattern is consistent with the evolution of tissue-specific function.