Abstract：
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.
摘要：
我们使用来自2548个母系的64,806个当代冰岛人的序列数据，研究了人类线粒体DNA（mtDNA）突变的速率和性质。根据116,663份母婴传输，检测到8,199个突变，按核苷酸类型提供稳健的速率估计，功能影响，position,和相同位置的不同等位基因。我们彻底记录了mtDNA中超突变的真实程度，主要影响控制区，但也影响一些编码区变体。结果揭示了负选择对可行的有害突变的影响，包括快速突变疾病相关的3243A>G和1555A>G和出生前选择，最可能发生在卵母细胞的发育过程中。最后,我们发现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播给孩子。
