We examined the rate and nature of mitochondrial DNA (mtDNA) mutations in humans using sequence data from 64,806 contemporary Icelanders from 2,548 matrilines. Based on 116,663 mother-child transmissions, 8,199 mutations were detected, providing robust rate estimates by nucleotide type, functional impact, position, and different alleles at the same position. We thoroughly document the true extent of hypermutability in mtDNA, mainly affecting the control region but also some coding-region variants. The results reveal the impact of negative selection on viable deleterious mutations, including rapidly mutating disease-associated 3243A>G and 1555A>G and pre-natal selection that most likely occurs during the development of oocytes. Finally, we show that the fate of new mutations is determined by a drastic germline bottleneck, amounting to an average of 3 mtDNA units effectively transmitted from mother to child.

我们使用来自 2,548 个母系的 64,806 名当代冰岛人的序列数据检查了人类线粒体 DNA (mtDNA) 突变的速率和性质。基于 116,663 例母婴传播，检测到 8,199 个突变，通过核苷酸类型、功能影响、位置和同一位置的不同等位基因提供可靠的比率估计。我们彻底记录了 mtDNA 超突变的真实程度，主要影响控制区，但也影响一些编码区变异。结果揭示了负选择对可行的有害突变的影响，包括快速突变的疾病相关 3243A>G 和 1555A>G 以及最有可能发生在卵母细胞发育过程中的产前选择。最后，我们表明新突变的命运是由严重的种系瓶颈决定的，平均有 3 个 mtDNA 单位有效地从母亲传递给孩子。