Mitochondrial–Nuclear Interactions: Compensatory Evolution or Variable Functional Constraint among Vertebrate Oxidative Phosphorylation Genes?

Abstract

Oxidative phosphorylation (OXPHOS), the major energy-producing pathway in aerobic organisms, includes protein subunits encoded by both mitochondrial (mt) and nuclear (nu) genomes. How these independent genomes have coevolved is a long-standing question in evolutionary biology. Although mt genes evolve faster than most nu genes, maintenance of OXPHOS structural stability and functional efficiency may involve correlated evolution of mt and nu OXPHOS genes. The nu OXPHOS genes might be predicted to exhibit accelerated evolutionary rates to accommodate the elevated substitution rates of mt OXPHOS subunits with which they interact. Evolutionary rates of nu OXPHOS genes should, therefore, be higher than that of nu genes that are not involved in OXPHOS (nu non-OXPHOS). We tested the compensatory evolution hypothesis by comparing the evolutionary rates (synonymous substitution rate dS and nonsynonymous substitution rate dN) among 13 mt OXPHOS genes, 60 nu OXPHOS genes, and 77 nu non-OXPHOS genes in vertebrates (7 fish and 40 mammal species). The results from a combined analysis of all OXPHOS subunits fit the predictions of the hypothesis. However, results from two OXPHOS complexes did not fit this pattern when analyzed separately. We found that the dN of nu OXPHOS genes for “core” subunits (those involved in the major catalytic activity) was lower than that of “noncore” subunits, whereas there was no significant difference in dN between genes for nu non-OXPHOS and core subunits. This latter finding suggests that compensatory changes play a minor role in the evolution of OXPHOS genes and that the observed accelerated nu substitution rates are due largely to reduced functional constraint on noncore subunits.

Pleistocene divergence across a mountain range and the influence of selection on mitogenome evolution in threatened Australian freshwater cod species

“…Amino acid replacements putatively under selection in the Mary River cod were located in complexes I (ND1, ND5 and ND6) and, somewhat atypically, in complex IV (COI, COII and COIII) (Zhang and Broughton, 2013). Whilst amino acid replacements in complex I (ND genes) tend to have minor effects on functional properties of amino acids, amino acid replacements in complex IV (COX genes) tend to have disproportionate effects on fitness, making COX genes typically the most highly conserved in the mitogenome (Zhang and Broughton, 2013).…”

“…Amino acid replacements putatively under selection in the Mary River cod were located in complexes I (ND1, ND5 and ND6) and, somewhat atypically, in complex IV (COI, COII and COIII) (Zhang and Broughton, 2013). Whilst amino acid replacements in complex I (ND genes) tend to have minor effects on functional properties of amino acids, amino acid replacements in complex IV (COX genes) tend to have disproportionate effects on fitness, making COX genes typically the most highly conserved in the mitogenome (Zhang and Broughton, 2013). Although sites showing signatures of episodic positive selection detected in the Mary River cod may represent false positives that are in fact deleterious but not (yet) removed by selection because of low effective population size, investigation of candidate sites and adaptive processes in Mary River cod seems warranted (Hughes, 2007).…”

Mitochondrial-Nuclear Epistasis Contributes to Phenotypic Variation and Coadaptation in Natural Isolates of Saccharomyces cerevisiae

“…The Dobzhansky-Muller-type mt-n incompatibilities that sometimes exist between species may have contributed to speciation events (Trier et al 2014;Wolff et al 2014), although the dynamics of mt-n coevolution are not well enough understood to make substantial conclusions. Regardless, the trove of molecular sequence analyses repeatedly has shown evidence for coevolution of mt-n complexes (e.g., BayonaBafaluy et al 2005;Parmakelis et al 2013;Zhang and Broughton 2013), supporting the empirical data that mt-n incompatibilities generally increase with genetic distance.The yeast S. cerevisiae is potentially an excellent model system to investigate mt-n epistasis. First, yeasts undergo both meiotic and mitotic replication.…”

The Roles of Mutation, Selection, and Expression in Determining Relative Rates of Evolution in Mitochondrial versus Nuclear Genomes

“…We refer to this as the nuclear compensation hypothesis, which has been supported by the following: (1) patterns of mitonuclear evolution such as the position and relative tim Popadin et al 2013;Zhang and Broughton 2013). We refer to this argument as the selective constraints hypothesis, which is supported by two main lines of reasoning.…”

“…We refer to this argument as the selective constraints hypothesis, which is supported by two main lines of reasoning. First, N-mt genes often encode "peripheral" subunits within OXPHOS complexes, which may be able to withstand more mutations due to a less critical role in OXPHOS (note that some of these peripheral subunits are eukaryotic-specific additions to these complexes and were not ancestrally present in bacteria; van der Sluis et al 2015), whereas mt genes encode "core" subunits, which may participate in more essential functions (Zhang and Broughton 2013). Secondly, proteins that are highly abundant may be under more functional constraints because protein misfolding and misinteractions can be more costly for abundant proteins, resulting in stronger purifying selection and slower evolution (Zhang and Yang 2015).…”