Mitochondrial DNA segregation in the developing embryo.
Mitochondrial DNA segregation in the developing embryo.
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DOI：
10.1093/humrep/15.suppl_2.229
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发表时间：
2000-07
影响因子：
6.1
通讯作者：
E. Shoubridge
中科院分区：
文献类型：
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作者：
E. Shoubridge
哺乳动物的线粒体（mt）DNA是严格的母系遗传;因此，新的突变沿着母系分离，而没有与父系来源的mtDNA同源重组的好处。尽管成熟卵母细胞的mtDNA拷贝数很高（约100000或更多），尽管卵子发生过程中细胞分裂的数量相对较少，但mtDNA序列变异在两代之间迅速分离。这种自相矛盾的行为被归因于卵子发生或早期胚胎发生中mtDNA的“瓶颈”。这一瓶颈的性质和规模一直备受争议。这篇综述认为，女性生殖系中mtDNA序列变异的分离主要发生在卵母细胞前体群体的有丝分裂过程中。分离是快速的，因为前体细胞（原始生殖细胞和卵原细胞）包含相对少量的mtDNA模板（瓶颈），并且因为mtDNA的复制处于宽松的控制之下。在大多数情况下，在小鼠分离多态性序列变体和人类谱系分离致病性点突变的过程似乎相似。特别是，没有证据表明在卵子发生、早期胚胎发育或胎儿发育中对高水平致病性mtDNA点突变的选择，因此表明有效的呼吸链功能直到出生后才是至关重要的。这些结果对临床遗传学具有重要的实际意义。
Mitochondrial (mt)DNA is strictly maternally inherited in mammals; new mutations thus segregate along maternal lineages without the benefit of homologous recombination with mtDNA of paternal origin. Despite the high mtDNA copy number (approximately 100000 or more) in mature oocytes, and despite the relatively small number of cell divisions during oogenesis, mtDNA sequence variants segregate rapidly between generations. This paradoxical behaviour has been ascribed to the presence of a mtDNA 'bottleneck' in oogenesis or early embryogenesis. The nature and size of this bottleneck have been the subject of much controversy. This review argues that segregation of mtDNA sequence variants in the female germline occurs primarily during mitosis in the oocyte precursor population. Segregation is rapid because the precursor cells (primordial germ cells and oogonia) contain a relatively small number of mtDNA templates (the bottleneck) and because the replication of mtDNA is under relaxed control. For the most part, the process appears similar in mice segregating polymorphic sequence variants and in human pedigrees segregating pathogenic point mutations. In particular, there is no evidence for selection against high levels of pathogenic mtDNA point mutations in oogenesis, in early embryonic development, or in fetal development, thus suggesting that efficient respiratory chain function is not critical until post-natal life. These results have important practical implications for clinical genetics.