Wai Timothy, Teoli Daniella, Shoubridge Eric A
Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal, Canada.
Nat Genet. 2008 Dec;40(12):1484-8. doi: 10.1038/ng.258.
In mammals, mitochondrial DNA (mtDNA) sequence variants are observed to segregate rapidly between generations despite the high mtDNA copy number in the oocyte. This has led to the concept of a genetic bottleneck for the transmission of mtDNA, but the mechanism remains contentious. Several studies have suggested that the bottleneck occurs during embryonic development, as a result of a marked reduction in germline mtDNA copy number. Mitotic segregation of mtDNAs during preimplantation, or during the expansion of primordial germ cells (PGCs) before they colonize the gonad, is thought to account for the increase in genotypic variance observed among mature oocytes from heteroplasmic mothers. This view has, however, been challenged by studies suggesting that the bottleneck occurs without a reduction in germline mtDNA content. To resolve this controversy, we measured mtDNA heteroplasmy and copy number in single germ cells isolated from heteroplasmic mice. By directly tracking the evolution of mtDNA genotypic variance during oogenesis, we show that the genetic bottleneck occurs during postnatal folliculogenesis and not during embryonic oogenesis.
在哺乳动物中，尽管卵母细胞中的线粒体DNA（mtDNA）拷贝数很高，但mtDNA序列变异在代与代之间仍能快速分离。这导致了mtDNA遗传瓶颈的概念，但其机制仍存在争议。多项研究表明，瓶颈出现在胚胎发育过程中，是生殖系mtDNA拷贝数显著减少的结果。人们认为，在植入前或原始生殖细胞（PGC）在定殖到性腺之前扩增期间，mtDNA的有丝分裂分离导致了异质母亲成熟卵母细胞中观察到的基因型变异增加。然而，这一观点受到了一些研究的挑战，这些研究表明瓶颈发生时生殖系mtDNA含量并未减少。为了解决这一争议，我们测量了从异质小鼠中分离出的单个生殖细胞中的mtDNA异质性和拷贝数。通过直接追踪卵母细胞发生过程中mtDNA基因型变异的演变，我们发现遗传瓶颈发生在出生后的卵泡发生过程中，而不是胚胎期卵母细胞发生过程中。
