EVOLUTION OF EUTHERIAN CYTOCHROME-C-OXIDASE SUBUNIT-II - HETEROGENEOUS RATES OF PROTEIN EVOLUTION AND ALTERED INTERACTION WITH CYTOCHROME-C

Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial g enome, exhibits one of the most heterogeneous rates of amino acid repl acement among placental mammals. Moreover, it has been demonstrated th at cytochrome c oxidase has undergone a structural change in higher pr imates which has altered its physical interaction with cytochrome c. W e collected a large data set of COII sequences from several orders of mammals with emphasis on primates, rodents, and artiodactyls. Using ph ylogenetic hypotheses based on data independent of the COII gene, we d emonstrated that an increased number of amino acid replacements are co ncentrated among higher primates. Incorporating approximate divergence dates derived from the fossil record, we find that most of the change occurred independently along the New World monkey lineage and in a ra pid burst before apes and Old World monkeys diverged. There is some ev idence that Old World monkeys have undergone a faster rate of nonsynon ymous substitution than have apes. Rates of substitution at four-fold degenerate sites in primates are relatively homogeneous, indicating th at the rate heterogeneity is restricted to nondegenerate sites. Exclud ing the rate acceleration mentioned above, primates, rodents, and arti odactyls have remarkably similar nonsynonymous replacement rates. A di fferent pattern is observed for transversions at four-fold degenerate sites, for which rodents exhibit a higher rate of replacement than do primates and artiodactyls. Finally, we hypothesize specific amino acid replacements which may account for much of the structural difference in cytochrome c oxidase between higher primates and other mammals.