Paternal leakage of mitochondrial DNA is genetically controlled in Drosophila

Abstract Mitochondrial DNA is generally assumed to be strictly maternally inherited, with paternal leakage treated as a rare stochastic error. Using hybrids from multiple Drosophila simulans isofemale lines crossed to D. mauritiana, we assayed heteroplasmy and asked whether leakage has a genetic basis. Leakage varied consistently among lines and families, replicated across independent experiments, and was markedly higher in males than females. Estimates indicated high heritability, and natural isofemale lines showed greater among-family variance than inbred laboratory stocks. These results demonstrate that paternal mtDNA leakage is under strong genetic control, rather than resulting from stochastic errors in the mechanisms that enforce strict maternal transmission, suggesting potential functional implications for long-term mitochondrial genome stability and evolution.