Sensitivity of genome-wide tests for mitonuclear genetic incompatibilities

Mismatches between interacting mitochondrial and nuclear gene products in hybrids have been proposed to disproportionately contribute to the formation of early species boundaries. Under this model, genetic incompatibilities emerge when mitochondrial haplotypes are placed into a cellular context without their coevolved nuclear-encoded mitochondrial (n-mt) proteins. Although there is strong evidence that mitonuclear coevolution has contributed to reproductive isolation in some cases, it is less clear how far-reaching the effects of mitonuclear incompatibilities are in speciation. Does disrupting co-adapted mitonuclear genotypes have broad, genome-wide effects with numerous n-mt loci contributing to reproductive isolation? We leverage a system with several hybridizing species pairs (Xiphophorus fishes) that have known mitonuclear incompatibilities of large effect to ask whether a general signal of incompatibility is present when considering all n-mt genes. After dividing nuclear-encoded proteins into three classes based on level of interaction with mitochondrial gene products, we found only inconsistent statistical evidence for a difference between these classes in the degree of conserved mitonuclear ancestry. Our results imply that genome-wide scans focused on enrichment of broad functional gene classes may sometimes be insufficient for detecting a history of mitonuclear coevolution, even when strong selection is acting on mitonuclear incompatibilities at multiple loci.