title: Adaptive selection of mitochondrial complex I subunits during primate radiation.
abstract: Mammalian oxidative phosphorylation (OXPHOS) complexes I, III, IV and V are assembled from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) encoded subunits, with complex I encompassing 39 nDNA and seven mtDNA subunits. Yet the sequence variation of the mtDNA genes is more than ten fold greater than that of the nDNA encoded genes of the OXPHOS complexes and the mtDNA proteins have been found to be influenced by positive (adaptive) selection. To maintain a functional complex I, nDNA and mtDNA subunits must interact, implying that certain nDNA complex I genes may also have been influenced by positive selection. To determine if positive selection has influenced nDNA complex I genes, we analyzed the DNA sequences of all of the nDNA and mtDNA encoded complex I subunits from orangutan, gorilla, chimpanzee, human and all available vertebrate sequences. This revealed that three nDNA complex I genes (NDUFC2, NDUFA1, and NDUFA4) had significantly increased amino acid substitution rates by both PAML and Z-test, suggesting that they have been subjected to adaptive selection during primate radiation. Since all three of these subunits reside in the membrane domain of complex I along with the mtDNA subunits, we compared amino acid changes in these three nDNA genes with those of the mtDNA genes across species. Changes in the nDNA NDUFC2 cysteine 39 were found to correlate with those in the mtDNA ND5 cysteine 330. Therefore, adaptive selection has influenced some nDNA complex I genes and nDNA and mtDNA complex I genes may have co-evolved.
authors.affiliation: The Center for Molecular and Mitochondrial Medicine and Genetics, Hewitt Hall, room 2014, University of California, Irvine, Irvine, CA 92697-3940, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Mishmar
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Pesini
authors.forename: Mariana
authors.initials: M
authors.lastname: Mondragon-Palomino
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.forename: Brandon
authors.initials: B
authors.lastname: Gaut
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics*; D019143:Evolution, Molecular; D006071:Gorilla gorilla / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics; D010802:Phylogeny; D011148:Pongo pygmaeus / Q000235:genetics; D011323:Primates / Q000235:genetics*; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: D004272:DNA, Mitochondrial; D004247:DNA; D042967:Electron Transport Complex I