Extreme heterogeneity of human mitochondrial DNA from organelles to populations

Contrary to the long-held view that most humans harbour only identical mitochondrial genomes, deep resequencing has uncovered unanticipated extreme genetic variation within mitochondrial DNA (mtDNA). Most, if not all, humans contain multiple mtDNA genotypes (heteroplasmy); specific patterns of variants accumulate in different tissues, including cancers, over time; and some variants are preferentially passed down or suppressed in the maternal germ line. These findings cast light on the origin and spread of mtDNA mutations at multiple scales, from the organelle to the human population, and challenge the conventional view that high percentages of a mutation are required before a new variant has functional consequences. Deep resequencing has revealed extreme genetic variation in mitochondrial genomes at multiple levels. This heterogeneity has implications for the origins of human mitochondrial DNA mutations as well as their impact on rare and common human diseases, including cancer.