title: Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa isoforms.
abstract: Cytochrome c oxidase (COX) consists of 13 subunits, 3 encoded in the mitochondrial genome and 10 in the nucleus. Little is known of the role of the nuclear-encoded subunits, some of which exhibit tissue-specific isoforms. Subunit VIa is unique in having tissue-specific isoforms in all mammalian species examined. We examined relative evolutionary rates for the COX6A heart (H) and liver (L) isoform genes along the length of the molecule, specifically in relation to the tissue-specific function(s) of the two isoforms. Nonsynonymous (amino acid replacement) substitutions in the COX6AH gene occurred more frequently than in the ubiquitously expressed COX6AL gene. Maximum-parsimony analysis and sequence divergences from reconstructed ancestral sequences revealed that after the ancestral COX6A gene duplicated to yield the genes for the H and L isoforms, the sequences encoding the mitochondrial matrix region of the COX VIa protein experienced an elevated rate of nonsynonymous substitutions relative to synonymous substitutions. This is expected for relaxed selective constraints after gene duplication followed by purifying selection to preserve the replacements with tissue-specific functions.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Schmidt
authors.forename: S A
authors.initials: SA
authors.lastname: Jaradat
authors.forename: M
authors.initials: M
authors.lastname: Goodman
authors.forename: M I
authors.initials: MI
authors.lastname: Lomax
authors.forename: L I
authors.initials: LI
authors.lastname: Grossman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003001:Cloning, Molecular; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D007527:Isoenzymes; D008099:Liver / Q000201:enzymology; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D010802:Phylogeny; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D007527:Isoenzymes; C472626:COX6A1 protein, human; C472628:Cox6a1 protein, mouse; D003576:Electron Transport Complex IV