title: Adaptive evolution of cytochrome c oxidase subunit VIII in anthropoid primates.
abstract: Cytochrome c oxidase (COX) is a 13-subunit protein complex that catalyzes the last step in mitochondrial electron transfer in mammals. Of the 10 subunits encoded by nuclear DNA (three are mtDNA products), some are expressed as tissue- and/or development-specific isoforms. For COX subunit VIII, previous work showed that expression of the contractile muscle-specific isoform gene, COX8H, is absent in humans and Old World monkeys, and the other isoform gene, COX8L, is expressed ubiquitously. Here, we show that COX8H is transcribed in most primate clades, but its expression is absent in catarrhines, that is, in Old World monkeys and hominids (apes, including humans), having become a pseudogene in the stem of the catarrhines. The ubiquitously expressed isoform, COX8L, underwent nonsynonymous rate acceleration and elevation in the ratio of nonsynonymous/synonymous changes in the stem of anthropoid primates (New World monkeys and catarrhines), possibly setting the stage for loss of the heart-type (H) isoform. The most rapidly evolving region of VIII-L is one that interacts with COX I, suggesting that the changes are functionally coadaptive. Because accelerated rates of nonsynonymous substitutions in anthropoids such as observed for COX8L are also shown by genes for at least 13 other electron transport chain components, these encoded amino acid replacements may be viewed as part of a series of coadaptive changes that optimized the anthropoid biochemical machinery for aerobic energy metabolism. We argue that these changes were linked to the evolution of an expanded neocortex in anthropoid primates.
authors.affiliation: Center for Molecular Medicine and Genetics and Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Allon
authors.initials: A
authors.lastname: Goldberg
authors.forename: Derek E
authors.initials: DE
authors.lastname: Wildman
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Schmidt
authors.forename: Maik
authors.initials: M
authors.lastname: Huttemann
authors.forename: Morris
authors.initials: M
authors.lastname: Goodman
authors.forename: Mark L
authors.initials: ML
authors.lastname: Weiss
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Grossman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002520:Cercopithecidae / Q000145:classification / Q000235:genetics*; D016384:Consensus Sequence; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D003576:Electron Transport Complex IV