Meeting Abstract
Mitochondria perform many key roles in their eukaryotic hosts, from integrating signaling pathways through to modulating whole organism phenotypes. The >1 billion years of nuclear and mitochondrial gene co-evolution has necessitated coordinated expression of proteins in the two-genome-encoded electron transport chain. How mitochondrial DNA (mtDNA) variation modifies host fitness has proved a challenging question but has profound implications for evolutionary and medical genetics. In Drosophila, we have previously shown that when mtDNA haplotype substitutions are performed in isogenic nuclear backgrounds, the amount of genetic distance between mtDNA molecules is a poor predictor of whole organism phenotypes. Crucially, underlying most phenotypic variation is protein abundance, which is ultimately regulated by gene expression. Here, we tested the effects of mtDNA haplotype variation on gene expression in Drosophila under standardized conditions. Using the Drosophila Genetic Reference Panel (DGRP), we constructed a panel of mitonuclear genotypes that consists of factorial variation in nuclear and mtDNA genomes, with mtDNAs originating in D. melanogaster (2x haplotypes) and D. simulans (2x haplotypes). We show that mtDNA haplotype variation unequivocally alters gene expression in both females and males, and mitonuclear interactions are pervasive modifying factors for gene expression. In females, there was enrichment for egg shell-related gene ontology terms with mtDNA haplotype variation, while males were enriched for chitinase activity-related genes. However, there was appreciable overlap between the sexes in those genes that were modified by mtDNA variation. We are now exploring these gene hubs in a systems biology context with the ultimate goal of characterizing predictable regulatory elements that are associated with mtDNA haplotype variation and gene expression.
