An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in Drosophila

Abstract

Mitochondrial transcription, translation, and respiration require interactions between genes encoded in two distinct genomes, generating the potential for mutations in nuclear and mitochondrial genomes to interact epistatically and cause incompatibilities that decrease fitness. Mitochondrial-nuclear epistasis for fitness has been documented within and between populations and species of diverse taxa, but rarely has the genetic or mechanistic basis of these mitochondrial–nuclear interactions been elucidated, limiting our understanding of which genes harbor variants causing mitochondrial–nuclear disruption and of the pathways and processes that are impacted by mitochondrial–nuclear coevolution. Here we identify an amino acid polymorphism in the Drosophila melanogaster nuclear-encoded mitochondrial tyrosyl–tRNA synthetase that interacts epistatically with a polymorphism in the D. simulans mitochondrial-encoded tRNATyr to significantly delay development, compromise bristle formation, and decrease fecundity. The incompatible genotype specifically decreases the activities of oxidative phosphorylation complexes I, III, and IV that contain mitochondrial-encoded subunits. Combined with the identity of the interacting alleles, this pattern indicates that mitochondrial protein translation is affected by this interaction. Our findings suggest that interactions between mitochondrial tRNAs and their nuclear-encoded tRNA synthetases may be targets of compensatory molecular evolution. Human mitochondrial diseases are often genetically complex and variable in penetrance, and the mitochondrial–nuclear interaction we document provides a plausible mechanism to explain this complexity.

Mitonuclear interactions: evolutionary consequences over multiple biological scales

“…Similarly, recent hybridization studies in the fruit fly revealed a pronounced mitonuclear incompatibility, which was traced specifically to the mtDNA encoded tRNA TYR of Drosophila simulans and the nuclear-encoded mitochondrial tyrosyl-tRNA synthetase of D. melanogaster [90]. This specific incompatibility decreases the activity of mETS complexes I, II and IV, compromises bristle formation, delays development and decreases fecundity [90]. A similar decline in OXPHOS capacity was previously documented in backcrosses of D. simulans and Drosophila mauritiana [91], and decreased fertility, fecundity and offspring viability, ultimately leading to hybrid breakdown in parasitoid wasps [92][93][94], and extensive mitonuclear epistatic interaction in the fruit fly [95].…”

Mitonuclear coevolution as the genesis of speciation and the mitochondrial DNA barcode gap

“…Many different mitochondrial and nuclear genes can be involved in hybrid incompatibilities, including subunits of the ETC and components of transcriptional and translational mechanisms (Burton and Barreto 2012; Meiklejohn et al. 2013; Levin et al. 2014; Hill 2015), but cytochrome c oxidase (complex IV) and cytochrome c are frequently implicated in incompatibilities (Rawson and Burton 2002; Sackton et al.…”

Reproductive isolation of hybrid populations driven by genetic incompatibilities

“…The first genetic model of speciation, described by Bateson, Dobzhansky and Muller (the BDM incompatibility model, S1 Fig., [22][23][24]), predicts that mutations at two genetic loci differentially accumulating along two lineages can negatively interact in their hybrids. Empirical research has shown that these types of negative epistatic interactions are remarkably common [25][26][27][28][29]; reviewed in [24,30,31].…”