A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes
A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes
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DOI：
10.1038/ng.2007.63
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发表时间：
2008-02-01
期刊：
影响因子：
30.8
通讯作者：
Chinnery, Patrick F.
中科院分区：
文献类型：
--
作者：
Cree, Lynsey M.;Samuels, David C.;Chinnery, Patrick F.
哺乳动物线粒体DNA（mtDNA）主要是沿着母系遗传的，但其机制尚未完全了解。携带突变型和野生型线粒体DNA混合物（异质性）的雌性将不同比例的突变型线粒体DNA遗传给其后代。在患有mtDNA疾病的人中，从母亲遗传的突变mtDNA的比例与疾病的严重程度相关（1-4）。等位基因频率的快速变化可以发生在一代人中（5，6）。这可能是由于从母亲传递给后代的mtDNA分子数量显著减少（线粒体遗传瓶颈），mtDNA被分配到同质分离单元中，或者选择一组mtDNA分子重新填充下一代。在这里，我们表明，线粒体DNA分子的分区到不同的细胞植入前后，其次是分离的复制之间的原始生殖细胞的线粒体DNA，是负责异质性雌性小鼠的后代中看到的异质性的不同水平。
Mammalian mitochondrial DNA (mtDNA) is inherited principally down the maternal line, but the mechanisms involved are not fully understood. Females harboring a mixture of mutant and wild-type mtDNA (heteroplasmy) transmit a varying proportion of mutant mtDNA to their offspring. In humans with mtDNA disorders, the proportion of mutated mtDNA inherited from the mother correlates with disease severity(1-4). Rapid changes in allele frequency can occur in a single generation(5,6). This could be due to a marked reduction in the number of mtDNA molecules being transmitted from mother to offspring (the mitochondrial genetic bottleneck), to the partitioning of mtDNA into homoplasmic segregating units, or to the selection of a group of mtDNA molecules to re-populate the next generation. Here we show that the partitioning of mtDNA molecules into different cells before and after implantation, followed by the segregation of replicating mtDNA between proliferating primordial germ cells, is responsible for the different levels of heteroplasmy seen in the offspring of heteroplasmic female mice.