A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes.

Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, Dahl HH, Chinnery PF
Nat Genet. 2008 40 (2): 249-54

PMID: 18223651 · DOI:10.1038/ng.2007.63

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.

MeSH Terms (32)

Alleles Animals Blastocyst Blastomeres Cell Lineage Chromosomal Proteins, Non-Histone Computer Simulation Crosses, Genetic DNA, Mitochondrial DNA Replication Embryo, Mammalian Embryonic Development Embryo Transfer Female Gene Dosage Gene Frequency Genetic Markers Genotype Green Fluorescent Proteins Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred CBA Mice, Inbred Strains Mice, Transgenic Microinjections Mitochondria Models, Genetic Oocytes Polymorphism, Genetic Pregnancy Repressor Proteins

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