The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells
@article{Cao2007TheMB, title={The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells}, author={Liqin Cao and Hiroshi Shitara and Takuro Horii and Yasumitsu Nagao and Hiroshi Imai and Kuniya Abe and Takahiko Hara and Jun-ichi Hayashi and Hiromichi Yonekawa}, journal={Nature Genetics}, year={2007}, volume={39}, pages={386-390} }
Observations of rapid shifts in mitochondrial DNA (mtDNA) variants between generations prompted the creation of the bottleneck theory. A prevalent hypothesis is that a massive reduction in mtDNA content during early oogenesis leads to the bottleneck. To test this, we estimated the mtDNA copy number in single germline cells and in single somatic cells of early embryos in mice. Primordial germ cells (PGCs) show consistent, moderate mtDNA copy numbers across developmental stages, whereas primary…
290 Citations
New Evidence Confirms That the Mitochondrial Bottleneck Is Generated without Reduction of Mitochondrial DNA Content in Early Primordial Germ Cells of Mice
- BiologyPLoS genetics
- 2009
Clear evidence is provided to confirm that no remarkable reduction in mt DNA content occurs in PGCs and reinforce that the bottleneck is generated without reduction of mtDNA content in germ cells.
A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes
- BiologyNature Genetics
- 2008
It is shown 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 ofheteroplasmic female mice.
The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes
- BiologyNature Genetics
- 2008
By directly tracking the evolution of mtDNA genotypic variance during oogenesis, it is shown that the genetic bottleneck occurs during postnatal folliculogenesis and not during embryonic oogenesis.
Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos
- BiologyNature Cell Biology
- 2017
It is shown that mtDNA copy number is reduced and non-synonymous mt DNA mutations are eliminated to prevent mtDNA mutation accumulation in germ cells during human primordial germ cell development, preventing the relentless accumulation of mtDNA mutations in the human population predicted by Muller’s ratchet.
Rapid mitochondrial DNA segregation in primate preimplantation embryos precedes somatic and germline bottleneck.
- BiologyCell reports
- 2012
Independent regulation of mtDNA quantity and quality resets the mitochondrial genome in C. elegans primordial germ cells
- BiologybioRxiv
- 2022
It is shown that PGCs generate a bottleneck in mtDNA number by segregating mitochondria into lobe-like protrusions that are cannibalized by adjacent cells, reducing mtDNA content two-fold, and that the kinase PINK1, operating independently of Parkin and autophagy, preferentially reduces the fraction of mutant mtDNAs.
Oxygen tension modulates the mitochondrial genetic bottleneck and influences the segregation of a heteroplasmic mtDNA variant in vitro
- BiologyCommunications biology
- 2021
Differences in oxygen tension occurring during early development likely modulate the amount of mtDNA, facilitating mtDNA segregation and contributing to tissue-specific mutation loads.
Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them
- BiologyPLoS genetics
- 2010
New evidence that some types of deleterious mtDNA mutations are eliminated within a few generations suggests that women undergoing PGD have a reasonable chance of generating embryos with a lower mutant load than their own.
What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations
- BiologyPhilosophical Transactions of the Royal Society B: Biological Sciences
- 2014
The consequences of life-history differences among taxa with respect to mtDNA evolution are discussed and a case for the use of microorganisms to experimentally manipulate levels of selection is made.
References
SHOWING 1-10 OF 32 REFERENCES
Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA
- BiologyNature Genetics
- 1996
It is shown that the pattern of segregation can be explained by random genetic drift ocurring in early oogenesis, and that the effective number of segregating units for mtDNA is ∼200 in mice, which provides the basis for estimating recurrence risks for mitochondrial disease due to pathogenic mt DNA mutations and for predicting the rate of fixation of neutral mtDNA mutations in maternal lineages.
Nuclear genetic control of mitochondrial DNA segregation
- BiologyNature Genetics
- 2003
It is shown that this phenotype segregates in F2 mice from a genetic cross (BALB/c × CAST/Ei) and that it maps to at least three quantitative-trait loci (QTLs) and is the first genetic evidence for nuclear control of mammalian mtDNA segregation.
Evidence from human oocytes for a genetic bottleneck in an mtDNA disease.
- BiologyAmerican journal of human genetics
- 1998
Oocytes from a patient with Kearn-Sayre syndrome caused by mtDNA rearrangements are examined to present direct evidence that the number of segregating units (n) is three to five orders of magnitude less than thenumber of mitochondria in the human female oocyte.
Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1995
It is concluded that cytoplasmic genomes are transmitted uniparentally in intraspecific crosses in mammals as in Chlamydomonas and that leakage of parental mtDNA is limited to interspecific crosses, which rarely occur in nature.
Skewed segregation of the mtDNA nt 8993 (T-->G) mutation in human oocytes.
- BiologyAmerican journal of human genetics
- 1997
Oocytes from a woman with heteroplasmic expression of the mtDNA nt 8993 (T-->G) mutation are studied, and it is found that subsequent mature oocytes may contain predominantly wild-type or mutant mitochondrial genomes.
Organization and dynamics of human mitochondrial DNA
- BiologyJournal of Cell Science
- 2004
It is demonstrated that nucleoids and respiratory complexes are mobile and diffuse efficiently into mitochondria previously devoid of mtDNA, and fusion-mediated exchange and intramitochondrial mobility of endogenous mitochondrial components are not rate-limiting for intermitochondrial complementation.
Nucleotide sequence evidence for rapid genotypic shifts in the bovine mitochondrial DNA D-loop
- BiologyNature
- 1983
The nucleotide sequence of all or part of the D-loop region in 14 maternally related Holstein cows is determined to help answer the question of how individual variant mtDNA molecules resulting from mutational events can come to dominate the large intracellular mtDNA population so rapidly.
Quantification of mtDNA in single oocytes, polar bodies and subcellular components by real-time rapid cycle fluorescence monitored PCR
- BiologyZygote
- 2000
The number of mitochondrial genomes present in mature mouse and human metaphase II oocytes was estimated by fluorescent rapid cycle DNA amplification, which is a highly sensitive technique ideally suited to quantitative mitochondrial DNA (mtDNA) analysis in individual cells.
Selective and continuous elimination of mitochondria microinjected into mouse eggs from spermatids, but not from liver cells, occurs throughout embryogenesis.
- BiologyGenetics
- 2000
Observations suggest that mitochondria from spermatids but not from liver have specific factors that ensure their selective elimination and resultant elimination of mtDNA in them, and that the occurrence of elimination is not limited to early stage embryos, but continues throughout embryogenesis.
Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos.
- BiologyDevelopmental biology
- 1987