Genomic Approaches to Evolutionary History of Primate Cytochromes c

Cytochrome c (cyt c) is a highly conserved protein among eukaryotes, mainly owing to its pivotal role in two crucial cellular processes: apoptosis and respiratory chain function. Despite its overall stability, previous studies have reported on the human lineage: (i) a high amino acid evolution rate of cyt c somatic isoform, (ii) absence of the testis isoform, and (iii) atypical biochemical behavior of human cyt c. In order to gain insight, we have investigated the cyt c loci and sequence evolution among primate lineages. Using cyt c sequences obtained by sequencing and from databases, genomic loci were obtained and compared using the UCSC Genome Browser. Phylogenetic statistical approaches were used to construct trees, to estimate divergence times, and to test selection models. Then potential effects of the changes were evaluated with spatial comparison and mathematical modeling. All the analyzed primate testis cyt c sequences share the same nonsense mutation, which suggests that the silencing occurred in the early primate stem. The phylogenetic analyses of somatic cyt c converged to the same tree topology recovering all major groups with maximal branch support. The evolutionary analyses show that strong positive selection occurs specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stem. Spatial analysis and mathematical modeling suggest that evolution specifically focus on the respiratory chain rather than apoptosis or other cyt c functions. Supported by previous biochemical studies, our results show that the silencing of the cyt c testis isoform is correlated with the decrease of primate reproduction and that the fast evolution of the cyt c somatic isoform is correlated with the increase of primate metabolism. Finally, the parallel evolution of cyt c in the two sister anthropoid groups leads us to propose that cyt evolution may in fact have participated in the evolutionary events with which its changes are correlated.