The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells
The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells
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DOI：
10.1038/ng1970
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发表时间：
2007-03-01
期刊：
影响因子：
30.8
通讯作者：
Yonekawa, Hiromichi
中科院分区：
文献类型：
--
作者：
Cao, Liqin;Shitara, Hiroshi;Yonekawa, Hiromichi
对线粒体DNA （mtDNA）变异在代际间快速变化的观察促使瓶颈理论的产生。一个普遍的假设是，在卵子发生早期mtDNA含量的大量减少导致了瓶颈（1,2）。为了验证这一点，我们估计了小鼠早期胚胎的单个生殖系细胞和单个体细胞的mtDNA拷贝数。原始生殖细胞（PGCs）在发育阶段表现出一致的、中等的mtDNA拷贝数，而初级卵母细胞在卵母细胞成熟早期表现出大量的mtDNA扩增。一些体细胞具有非常低的mtDNA拷贝数。我们还证明了PGCs每个细胞有超过100个线粒体。我们得出的结论是，线粒体瓶颈不是由于早期卵子发生时mtDNA拷贝数的急剧下降，而是由于小鼠生殖细胞中mtDNA的有效分离单位数量较少。这些结果为建立mtDNA分离模型和了解mtDNA疾病的复发风险提供了新的信息。
Observations of rapid shifts in mitochondrial DNA (mtDNA) variants between generations prompted the creation of the bottleneck theory. A prevalent hypothesis is that a massive reduction in mtDNA content during early oogenesis leads to the bottleneck(1,2). To test this, we estimated the mtDNA copy number in single germline cells and in single somatic cells of early embryos in mice. Primordial germ cells (PGCs) show consistent, moderate mtDNA copy numbers across developmental stages, whereas primary oocytes demonstrate substantial mtDNA expansion during early oocyte maturation. Some somatic cells possess a very low mtDNA copy number. We also demonstrated that PGCs have more than 100 mitochondria per cell. We conclude that the mitochondrial bottleneck is not due to a drastic decline in mtDNA copy number in early oogenesis but rather to a small effective number of segregation units for mtDNA in mouse germ cells. These results provide new information for mtDNA segregation models and for understanding the recurrence risks for mtDNA diseases.