(10d) Automated Computational Analysis of Molecular Evolution: Mitochondrial ATP Synthase in Primates and Other Mammals

Mitochondrial ATP synthase ? the fifth and final complex of the mitochondrial electron transport system (ETS) ? converts potential energy into ATP, the principal energy source in all cells. Because of their fundamental importance in sustaining life, ATP synthases are thought to be highly conserved enzymes, with similar structures and functions in both eukaryotes and bacteria. Here we investigate whether the pattern of relatively rapid evolutionary rates observed in primates for other ETS complexes holds for this complex, complex V, as well. We present an on-line, automated analytic tool that 1) extracts orthologous protein coding nucleotide sequences from public databases; 2) generates in-frame multiple alignments, and; 3) performs inferential statistical tests of natural selection. Analyses of 16 nuclear-encoded subunits in 11 taxa indicate that, despite low overall dN/dS rates, the complex shows evidence of higher rates in primates relative to rodents and to other sampled vertebrates. This pattern is also evident in separate analyses of the membrane-bound (F1) subunits, comprising the complex's catalytic core, and the membrane-spanning (F0) subunits, comprising the complex's proton channel. Analyses of an independent concatenated data set comprising the genes encoding Complex V assembly and inhibitory proteins confirm the pattern of relatively higher rates in primates. Expanded data sets of one gene each from Fo (subunit B, n=22) and F1 (a subunit, n=17) confirm relatively higher rates in primates for the former, in particular among the anthropoids. Finally, SNP analyses indicate that the a subunit is the only nuclear-encoded complex V subunit showing a significant excess of non-synonymous polymorphic substitutions within humans.