Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa isoforms

Molecular Biology and Evolution
Timothy R SchmidtL I Grossman

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.

Citations

Feb 14, 2006·Journal of Molecular Evolution·Weilong Hao, G Brian Golding
Feb 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Monica UddinMorris Goodman
Apr 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Allon GoldbergLawrence I Grossman
Jan 14, 2003·Annual Review of Physiology·Christopher D Moyes, David A Hood
Jan 17, 2008·BMC Evolutionary Biology·Monica UddinLawrence I Grossman
Apr 18, 2013·PloS One·Corinne E GriguerClaudia R Oliva
Aug 2, 2011·Biochimica Et Biophysica Acta·Denis PierronLawrence I Grossman
Mar 27, 2001·Molecular Biology and Evolution·T R SchmidtL I Grossman
Mar 11, 2000·Molecular Biology and Evolution·D S Gonzalez, I K Jordan
Dec 3, 2004·Molecular Biology and Evolution·Maria Pilar Bayona-BafaluyCarlos T Moraes
Dec 14, 2007·The Journal of Biological Chemistry·Shilpa S DharMargaret T T Wong-Riley
Jun 9, 2017·Oxidative Medicine and Cellular Longevity·Christopher A SinklerMaik Hüttemann

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