title: A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes.
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.
authors.affiliation: Mitochondrial Research Group, Newcastle University, Newcastle NE2 4HH, UK.
authors.forename: Lynsey M
authors.initials: LM
authors.lastname: Cree
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.forename: Susana Chuva
authors.initials: SC
authors.lastname: de Sousa Lopes
authors.forename: Harsha Karur
authors.initials: HK
authors.lastname: Rajasimha
authors.forename: Passorn
authors.initials: P
authors.lastname: Wonnapinij
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Mann
authors.forename: Hans-Henrik M
authors.initials: HH
authors.lastname: Dahl
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000737:chemistry / Q000166:cytology; D001757:Blastomeres / Q000737:chemistry; D019070:Cell Lineage; D002868:Chromosomal Proteins, Non-Histone; D003198:Computer Simulation; D003433:Crosses, Genetic; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000737:chemistry* / Q000235:genetics*; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000737:chemistry / Q000166:cytology; D047108:Embryonic Development; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008845:Microinjections; D008928:Mitochondria / Q000737:chemistry*; D008957:Models, Genetic; D009865:Oocytes / Q000737:chemistry; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004272:DNA, Mitochondrial; C462180:Dppa3 protein, mouse; D005819:Genetic Markers; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins