COX5A (cytochrome c oxidase subunit Va)

COX5A is one of the 10 nuclear encoded subunits of cytochrome c oxidase, the terminal protein of the mitochondrial electron transport chain. Many of these subunits (9 of 13) have undergone accelerated evolution in anthropoid ancestral lineages, although in non-anthropoid lineages they are typically conserved. The accelerated evolution, which has the properties of Darwinian positive selection, has been hypothesized to result from the energy needs of an expanded neocortex. Phylogenetic analysis of other COX subunits showed that for 8 of the 9 COX subunits showing accelerated nonsynonymous substitution, acceleration has taken place on two or all three of the anthropoid, catarrhine, and hominid stems. In the case of COX5A, however, two substitutions have also taken place since the divergence of Homo and Pan from a common ancestor. Although the function of COX5A is unknown, a speculative role in better energy regulation is reasonable because COX5A was shown to be a target of thyroid hormone T2 and because of the location of the anthropoid changed sites in the mitochondrial matrix, close to coevolving sites in subunits 2 and 4 proposed to have a COX regulatory function.

Type of Human-Specific Changes in COX5A: Thr(64) -> Leu; Ala(70) -> Val
Functional Differences in protein coding sequences