Mitochondrial genome variation affects the mutation rate of the nuclear genome in Drosophila melanogaster

Mutations are the raw material for evolutionary change. While the mutation rate has been thought constant between individuals, recent research has shown that poor genetic condition can elevate the mutation rate. Mitonuclear genetic conflict is a potential source of poor genetic condition, and considering the high mutation rate of mitochondrial genomes, there should be ample scope for mitochondrial mutations to interfere with genetic condition, with concomitant effects on the nuclear mutation rate. Moreover, because theory suggests mitochondrial genetic effects will often be male-biased, such effects could be more strongly felt in males than females. Here, by mating irradiated male Drosophila melanogaster to isogenic females bearing six distinct mitochondrial haplotypes, we tested whether mitochondrial genetic variation affects DNA repair capacity, and whether effects of mutation load on reproductive function are shaped by interactions between sex and mitochondrial haplotype. We found mitochondrial genetic effects on DNA repair, and that the mutational variance of reproductive fitness was higher in males bearing haplotypes characterized by high female fitness. These results suggest that mitochondrial genome variation may affect the mutation rate, and that induced mutations interact more strongly with male than female reproductive function. The potential for haplotype-specific effects on the nuclear mutation rate has broad implications for evolutionary dynamics, such as the accumulation of genetic load, adaptive potential, and the evolution of sexual dimorphism.