Relaxed selection on male mitochondrial genes in DUI bivalves eases the need for mitonuclear coevolution.

Mitonuclear coevolution is an important prerequisite for efficient energy production in eukaryotes. However, many bivalve taxa experience doubly uniparental inheritance (DUI) and have sex-specific mitochondrial (mt) genomes, providing a challenge for mitonuclear coevolution. We examined possible mechanisms to reconcile mitonuclear coevolution with DUI. No nuclear-encoded, sex-specific OXPHOS paralogs were found in the DUI clam Ruditapes philippinarum, refuting OXPHOS paralogy as a solution in this species. It is also unlikely that mt changes causing disruption of nuclear interactions are strongly selected against because sex-specific mt-residues or those under positive selection in M mt genes were not depleted for contacting nuclear-encoded residues. However, M genomes showed consistently higher dN /dS ratios compared to putatively ancestral F genomes in all mt OXPHOS genes and across all DUI species. Further analyses indicated that this was consistently due to relaxed, not positive selection on M vs. F mt OXPHOS genes. Similarly, selection was relaxed on the F genome of DUI species compared to species with strict maternal inheritance. Coupled with recent physiological and molecular evolution studies, we suggest that relaxed selection on M mt function limits the need to maintain mitonuclear interactions in M genomes compared to F genomes. We discuss our findings with regard to OXPHOS function and the origin of DUI.

Sexually Antagonistic Mitonuclear Coevolution in Duplicate Oxidative Phosphorylation Genes.

Mitochondrial function is critical in eukaryotes. To maintain an adequate supply of energy, precise interactions must be maintained between nuclear- and mitochondrial-encoded gene products. Such interactions are paramount in chimeric enzymes such as the oxidative phosphorylation (OXPHOS) complexes. Mutualistic coevolution between the two genomes has therefore been suggested to be a critical, ubiquitous feature of eukaryotes that acts to maintain cellular function. However, mitochondrial genomes can also act selfishly and increase their own transmission at the expense of organismal function. For example, male-harming mutations are predisposed to accumulate in mitochondrial genomes due to their maternal inheritance ("mother's curse"). Here, we investigate sexually antagonistic mitonuclear coevolution in nuclear-encoded OXPHOS paralogs from mammals and Drosophila. These duplicate genes are highly divergent but must interact with the same set of mitochondrial-encoded genes. Many such paralogs show testis-specific expression, prompting previous hypotheses suggesting they may have evolved under selection to counteract male-harming mitochondrial mutations. We found increased rates of evolution in OXPHOS paralogs with testis-specific expression in mammals and Drosophila, supporting this hypothesis. However, further analyses suggested such patterns may be due to relaxed, not positive selection, especially in Drosophila. Structural data also suggest that mitonuclear interactions do not play a major role in the evolution of many OXPHOS paralogs in a consistent way. In conclusion, no single OXPHOS paralog met all our criteria for being under selection to counteract male-harming mitochondrial mutations. We discuss alternative explanations for the drastic patterns of evolution in these genes, including mutualistic mitonuclear coevolution, adaptive subfunctionalization after gene duplication, and relaxed selection on OXPHOS in male tissues.