Selfish mitochondria exploit nutrient status across different levels of selection

Cooperation and cheating are widespread evolutionary strategies. Competition can simultaneously favor cheating within groups and cooperation between groups. Selfish or cheater mitochondrial DNA (mtDNA) mutants proliferate within hosts while being selected against at the level of host fitness. How does environment govern competition between cooperators and cheaters across different selection levels? Focusing on food availability, we address this question using heteroplasmic Caenorhabditis elegans. We show that by promoting germline development, nutrient status provides the niche space for mtDNA variants to compete. However, the within-host advantage of selfish mtDNA requires additional conditions, namely the FoxO transcription factor DAF-16. During food scarcity, DAF-16 mitigates the host fitness cost of the selfish mtDNA. We conclude that food availability, and resilience to food scarcity, govern selfish mtDNA dynamics across the levels of selection. Our study integrates an evolutionary framework with experimentation to identify cellular mechanisms underlying the multilevel selection that characterizes cheater dynamics.