Evolutionary trajectories are contingent on mitonuclear interactions

Critical mitochondrial functions, including cellular respiration, rely on frequently interacting components expressed from both the mitochondrial and nuclear genomes. The fitness of eukaryotic organisms depends on a tight collaboration between both genomes. In the face of an elevated rate of evolution in the mitochondrial genome, current models predict that maintenance of mitonuclear compatibility relies on compensatory evolution of the nuclear genome. Mitonuclear interactions would therefore exert a strong influence on evolutionary trajectories. One prediction from this model is that the same nuclear genomes but evolving with different mitochondrial haplotypes would follow distinct molecular paths towards higher fitness peaks. To test this prediction, we submitted 1344 populations derived from seven mitonuclear genotypes of Saccharomyces cerevisiae to more than 300 generations of experimental evolution in conditions that either select for a mitochondrial function, or that do not strictly require this organelle for survival. Performing high-throughput phenotyping and whole-genome sequencing on independently evolved individuals isolated from endpoint populations, we identified numerous examples of gene-level evolutionary convergence among populations with the same mitonuclear background. We recapitulated a subset of prominent loss-of-function alleles in the ancestral backgrounds. This confirmed a generalized pattern of mitonuclear-specific and highly epistatic fitness effects. Together, these results demonstrate how mitonuclear interactions can dictate evolutionary divergence of populations with identical starting nuclear genotypes.