Mitochondrial–Nuclear Interactions and Accelerated Compensatory Evolution: Evidence from the Primate Cytochrome c Oxidase Complex

Abstract

Accelerated rates of mitochondrial protein evolution have been proposed to reflect Darwinian coadaptation for efficient energy production for mammalian flight and brain activity. However, several features of mammalian mtDNA (absence of recombination, small effective population size, and high mutation rate) promote genome degradation through the accumulation of weakly deleterious mutations. Here, we present evidence for "compensatory" adaptive substitutions in nuclear DNA- (nDNA) encoded mitochondrial proteins to prevent fitness decline in primate mitochondrial protein complexes. We show that high mutation rate and small effective population size, key features of primate mitochondrial genomes, can accelerate compensatory adaptive evolution in nDNA-encoded genes. We combine phylogenetic information and the 3D structure of the cytochrome c oxidase (COX) complex to test for accelerated compensatory changes among interacting sites. Physical interactions among mtDNA- and nDNA-encoded components are critical in COX evolution; amino acids in close physical proximity in the 3D structure show a strong tendency for correlated evolution among lineages. Only nuclear-encoded components of COX show evidence for positive selection and adaptive nDNA-encoded changes tend to follow mtDNA-encoded amino acid changes at nearby sites in the 3D structure. This bias in the temporal order of substitutions supports compensatory weak selection as a major factor in accelerated primate COX evolution.

Positive Selection in Rapidly Evolving Plastid–Nuclear Enzyme Complexes

“…Adaptive changes in one genome may alter fitness landscapes and facilitate subsequent adaptive changes in the other genome, though it is unclear what forces might trigger such runaway adaptive evolution in these systems. A more conventional model of compensatory change in the nucleus in response to accumulation of deleterious changes in asexual organelle genomes (Rand et al 2004;Osada and Akashi 2012) seems less likely, particularly for the CLP complex, given the evidence that accelerated rates of sequence evolution in the plastid-encoded clpP1 evolution are driven largely by positive selection (Erixon and Oxelman 2008;Sloan et al 2012a;Barnard-Kubow et al 2014).…”

Weak Selection and Protein Evolution

“…Because fitness remains constant and genetic drift drives double-mutant substitution, we refer to such cases as "compensatory neutral" (CN). Weakly deleterious mutations can go to fixation at appreciable rates, and we refer to the restoration of fitness by subsequent, positively selected mutations as "compensatory weak selection" (CWS) (Osada and Akashi 2012). Note, however, that such mutations can confer large fitness benefits if they compensate for multiple deleterious fixations.…”

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“…The sample included female seniors majoring in philosophy, or those who recently earned a Bachelor's degree in it (N = 11, Age range: [18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Participants were recruited via email by convenience sampling at colleges and universities in the United States.…”

“…27 In 1923, the British government granted APOC control of an Iraqi railway line in Khanakin City, which gave APOC exclusivity for that particular line of 27½ miles in length. 28 According to Sluglett in Britain in Iraq, the Iraqi government concluded that more liberal control over the Iraqi railways may lead to a more amicable relationship with Britain. The Iraqi governments "only hope for amelioration lay in tinkering with the details of the Anglo-Iraqi relationship, and trusting that Britain might eventually be persuaded."…”