Max Planck Institute for Biology of Ageing, Cologne, Germany.
Wellcome Centre for Mitochondrial Research, Newcastle University Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Nat Rev Genet. 2021 Feb;22(2):106-118. doi: 10.1038/s41576-020-00284-x. Epub 2020 Sep 28.
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.
与长期以来认为大多数人类仅拥有相同线粒体基因组的观点相反，深度重测序揭示了线粒体 DNA（mtDNA）中出人意料的极端遗传变异。如果不是所有，那么大多数人都包含多种 mtDNA 基因型（异质性）；随着时间的推移，变体的特定模式会在不同组织中积累，包括癌症；一些变体在母系生殖系中更倾向于传递或抑制。这些发现揭示了 mtDNA 突变在多个尺度上的起源和传播，从细胞器到人类群体，并挑战了传统观点，即需要达到较高的突变比例，新变体才会产生功能后果。
