Letter abstract


Nature Genetics 40, 1484 - 1488 (2008)
Published online: 23 November 2008 | doi:10.1038/ng.258

The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes

Timothy Wai1, Daniella Teoli1 & Eric A Shoubridge1

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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 mtDNA1, 2, 3, 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 number4, 5. Mitotic segregation of mtDNAs during preimplantation5, or during the expansion of primordial germ cells (PGCs) before they colonize the gonad4, 5, 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 content6. 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.

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  1. Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal H3A 2B4, Canada.

Correspondence to: Eric A Shoubridge1 e-mail: eric@ericpc.mni.mcgill.ca



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