The units of selection on mitochondrial DNA

Mitochondrial DNA (mtDNA) exists in a nested hierarchy of populations. There are multiple mtDNAs within each mitochondrion, a population of mitochondria in each cell, multiple oocytes within each reproductive female, multiple females in each population, and so on up through species and higher clades. The metabolic properties of mitochondria make them highly mutagenic environments for the naked, circular mtDNAs that lie within them. This mutational pressure introduces mtDNA variation (i.e., heteroplasmy) into the cytoplasmic population of cell lineages that are particularly prone to mutational decay and Muller's ratchet owing to the asexual, maternal inheritance of mtDNA. Neutrality tests show that deleterious mutations are common in mtDNA evolution. Population cage experiments further show that mtDNA fitnesses are influenced by nuclear-mitochondrial interactions. These selective processes are pervasive despite the long-standing use of mtDNA as a neutral marker in population and evolutionary biology. These evolutionary dynamics are also unique in the nested hierarchy of mtDNA populations because mutation, selection, and drift can act-and interact-at multiple levels. Multi-level selection can facilitate the escape from Muller's ratchet and help resolve intragenomic conflicts. This review addresses recent advances in the transmission genetics, population genetics, and evolution of mtDNA. A primary goal of the review is to motivate additional empirical studies that might clarify the many units of selection acting on mtDNA.