Rethinking mitochondrial heteroplasmy: selection, conflict and adaptation

Abstract Mitochondrial DNA (mtDNA) variation is increasingly recognized for its role in shaping evolutionary changes at the species and population levels. Yet, its evolutionary relevance within individuals remains less explored. Eukaryotic cells typically carry multiple copies of mtDNA. When these copies differ in sequence, heteroplasmy arises—a form of intra-organismal genetic diversity with potentially profound biological implications. To elucidate the evolutionary significance of heteroplasmy in animals, we first review how natural selection shapes adaptive mtDNA dynamics at broader biological levels, via cases of mito-nuclear coadaptation, environmental-mediated and sex-specific selection and balancing selection. We then explore whether analogous selective pressures may operate at the intra-individual level. Heteroplasmy introduces the potential for multi-level selection—from the genome to the organism—potentially yielding synergistic or antagonistic evolutionary outcomes. This framework encompasses both the selfish transmission of certain mtDNA variants and emerging evidence for adaptive shifts in heteroplasmy levels under environmental stress. These findings are supported by theoretical models suggesting that paternal mtDNA transmission—historically viewed as a stochastic anomaly—may confer adaptive benefits under specific ecological and evolutionary contexts by introducing intra-individual mtDNA diversity. Collectively, these insights suggest that heteroplasmy may act as an underappreciated reservoir of adaptive potential, enhancing the evolutionary capacity of organisms in a changing world. This article is part of the theme issue ‘Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya’.