RT Journal Article SR Electronic T1 Mitochondrial DNA has strong selective effects across the nuclear genome JF bioRxiv FD Cold Spring Harbor Laboratory SP 643056 DO 10.1101/643056 A1 Timothy M. Healy A1 Ronald S. Burton YR 2019 UL http://biorxiv.org/content/early/2019/05/20/643056.abstract AB Oxidative phosphorylation requires gene products encoded in both the nuclear and mitochondrial genomes, and is the primary source of cellular energy in eukaryotes. As a result, functional integration between the genomes is essential for efficient ATP generation in these organisms. Although within populations this integration is presumably maintained by coevolution, both the importance of coevolution in speciation and mitochondrial disease, and the strength of selection for maintenance of coevolved genotypes are widely questioned. In this study, we crossed populations of the intertidal copepod, Tigriopus californicus, to disrupt putatively coevolved mitonuclear genotypes in reciprocal F2 hybrids. We utilized inter-individual variation in developmental rate, a proxy for fitness, among these hybrids to assess the strength of selection imposed on the nuclear genome by alternate mitochondrial genotypes. There was substantial variation in developmental rate among hybrid individuals, and in vitro ATP synthesis rates of mitochondria isolated from high fitness hybrids were approximately twice those of mitochondria isolated from low fitness individuals. Furthermore, we used Pool-seq to reveal large deviations in nuclear allele frequencies in hybrids, which favored maternal alleles in only high fitness individuals of each reciprocal cross. Therefore, our most fit hybrids had partial recovery of coevolved genotypes, indicating that mitonuclear effects underlie individual-level variation in developmental rate and that inter-genomic compatibility is critical for high fitness. These results demonstrate that mitonuclear interactions have profound impacts on both physiological performance and the evolutionary trajectory of the nuclear genome.