Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Nat Commun. 2020 Apr 8;11(1):1740. doi: 10.1038/s41467-020-15336-3.
Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans.
有几方面的证据对人类线粒体 DNA（mtDNA）仅沿母系遗传的教条提出了质疑，最近在三个家族中发现了几种个体携带有与双亲遗传一致的“异质合子单倍型”。在这里，我们在 11035 个三核苷酸重复序列中的 7 个中报告了类似的遗传特征，等位基因分数为 5-25%，这意味着 mtDNA 在 0.06%的后代中存在双亲遗传。然而，分析核全基因组序列，我们观察到在所有 7 个家族中，可能存在大量罕见或独特的核-线粒体 DNA 片段（mega-NUMTs）从父亲传递。在所有 0.13%的父亲中独立检测到 mega-NUMTs，我们看到了单倍型的常染色体遗传。最后，我们表明单倍型等位基因分数可以通过在核基因组内重排的复杂串联 mtDNA 衍生序列来解释。我们得出结论，罕见的隐性 mega-NUMTs 可能类似于父系 mtDNA 异质性，但在人类中没有发现 mtDNA 父系遗传的证据。
