Identification of Specific Nuclear Genetic Loci and Genes That Interact With the Mitochondrial Genome and Contribute to Fecundity in Caenorhabditis elegans

Previous studies have found that fecundity is a multigenic trait regulated, in part, by mitochondrial-nuclear (mit-n) genetic interactions. However, the identification of specific nuclear genetic loci or genes interacting with the mitochondrial genome and contributing to the quantitative trait fecundity is an unsolved issue. Here, a panel of recombinant inbred advanced intercrossed lines (RIAILs), established from a cross between the N2 and CB4856 strains of C. elegans, were used to characterize the underlying genetic basis of mit-n genetic interactions related to fecundity. Sixty-seven single nucleotide polymorphisms (SNPs) were identified by association mapping to be linked with fecundity among 115 SNPs linked to mitotype. This indicated significant epistatic effects between nuclear and mitochondria genetics on fecundity. In addition, two specific nuclear genetic loci interacting with the mitochondrial genome and contributing to fecundity were identified. A significant reduction in fecundity was observed in the RIAILs that carried CB4856 mitochondria and a N2 genotype at locus 1 or a CB4856 genotype at locus 2 relative to the wild-type strains. Then, a hybrid strain (CNC10) was established, which was bred as homoplasmic for the CB4856 mtDNA genome and N2 genotype at locus 1 in the CB4856 nuclear background. The mean fecundity of CNC10 was half the fecundity of the control strain. Several functional characteristics of the mitochondria in CNC10 were also influenced by mit-n interactions. Overall, experimental evidence was presented that specific nuclear genetic loci or genes have interactions with the mitochondrial genome and are associated with fecundity. In total, 18 genes were identified using integrative approaches to have interactions with the mitochondrial genome and to contribute to fecundity.