Interactions between cytoplasmic and nuclear genomes confer sex-specific effects on lifespan in Drosophila melanogaster

A large body of studies has demonstrated that genetic variation that resides outside of the cell nucleus can affect the organismal phenotype. The cytoplasm is home to the mitochondrial genome and, at least in arthropods, often hosts intracellular endosymbiotic bacteria such as Wolbachia. While numerous studies have implicated epistatic interactions between cytoplasmic and nuclear genetic variation as key to mediating patterns of phenotypic expression, two outstanding questions remain. Firstly, the relative contribution of mitochondrial genetic variation to other cytoplasmic sources of variation in shaping the phenotypic outcomes of cyto-nuclear interactions remains unknown. Secondly, it remains unclear whether the outcomes of cyto-nuclear interactions will manifest differently across the two sexes, as might be predicted given that cytoplasmic genomes are screened by natural selection only through females as a consequence of their maternal inheritance. Here, we address these questions, creating a fully-crossed set of replicated cyto-nuclear populations derived from three geographically distinct populations of Drosophila melanogaster, and measuring the lifespan of males and females from each population. We report cyto-nuclear interactions for lifespan, with the outcomes of these interactions differing across the sexes, and reconcile these findings with information on the full mitochondrial sequences and Wolbachia infection status of each of the populations.