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- Title
A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes.
- Authors
Cree, Lynsey M.; Samuels, David C.; de Sousa Lopes, Susana Chuva; Rajasimha, Harsha Karur; Wonnapinij, Passorn; Mann, Jeffrey R.; Dahl, Hans-Henrik M.; Chinnery, Patrick F.
- Abstract
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. Rapid changes in allele frequency can occur in a single generation. 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.
- Subjects
GENETIC polymorphisms; MITOCHONDRIAL DNA; MESSENGER RNA; MEMBRANE proteins; GENETIC mutation; CHROMOSOME abnormalities
- Publication
Nature Genetics, 2008, Vol 40, Issue 2, p249
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2007.63