Amino acid replacement is rapid in primates for the mature polypeptides of COX subunits, but not for their targeting presequences.

We examined inferred amino acid replacements for 16 genes that encode the proteins of the cytochrome c oxidase (COX) holoenzyme in eight vertebrate species. Phylogeny-based analysis revealed that the human lineage (primates) has had an unusually large, statistically significant, number of amino acid replacements in the mature protein coding region of these genes. This finding is similar to earlier observations of an accelerated non-synonymous substitution rate for some lineages of primates for COX1, COX2, COX4, and COX7AH. In contrast, the mitochondrial targeting presequences of these same proteins have not undergone a concomitant rate change. This more comprehensive analysis suggests that COX5A, COX6B, COX6C, COX7C, and COX8L have also undergone an acceleration in amino acid replacement rates in anthropoid primates. Some of these rate accelerations (e.g. in COX5A and COX7C) are so pronounced that non-human mammalian sequences are more similar to sequences from Xenopus or zebrafish than they are to human. Since the functions of the targeting and mature proteins of these polypeptides are different, the mature portions of these genes are likely to have undergone a functionally significant change that is adaptive in nature.