Editing Mitochondrial DNA (section)

=== The mitochondrial bottleneck ===
Entities subject to uniparental inheritance and with little to no recombination may be expected to be subject to [[Muller's ratchet]], the accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this through a developmental process known as the [[Heteroplasmy#Mitochondrial bottleneck|mtDNA bottleneck]]. The bottleneck exploits [[cellular noise|random processes in the cell]] to increase the cell-to-cell variability in [[heteroplasmy|mutant load]] as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo in which different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilisation or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated,<ref>{{Cite journal |vauthors=Wolff JN, White DJ, Woodhams M, White HE, Gemmell NJ |year=2011 |title=The strength and timing of the mitochondrial bottleneck in salmon suggests a conserved mechanism in vertebrates |journal=PLOS ONE |volume=6 |issue=5 |pages=e20522 |bibcode=2011PLoSO...620522W |doi=10.1371/journal.pone.0020522 |pmc=3105079 |pmid=21655224 |doi-access=free}}</ref><ref>{{Cite journal |display-authors=6 |vauthors=Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, Dahl HH, Chinnery PF |date=February 2008 |title=A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes |journal=Nature Genetics |volume=40 |issue=2 |pages=249–254 |doi=10.1038/ng.2007.63 |pmid=18223651 |s2cid=205344980}}</ref><ref>{{Cite journal |display-authors=6 |vauthors=Cao L, Shitara H, Horii T, Nagao Y, Imai H, Abe K, Hara T, Hayashi J, Yonekawa H |date=March 2007 |title=The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells |journal=Nature Genetics |volume=39 |issue=3 |pages=386–390 |doi=10.1038/ng1970 |pmid=17293866 |s2cid=10686347}}</ref><ref>{{Cite journal |vauthors=Wai T, Teoli D, Shoubridge EA |date=December 2008 |title=The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes |journal=Nature Genetics |volume=40 |issue=12 |pages=1484–1488 |doi=10.1038/ng.258 |pmid=19029901 |s2cid=225349}}</ref> with a recent mathematical and experimental metastudy providing evidence for a combination of the random partitioning of mtDNAs at cell divisions and the random turnover of mtDNA molecules within the cell.<ref name="pmid26035426">{{Cite journal |display-authors=6 |vauthors=Johnston IG, Burgstaller JP, Havlicek V, Kolbe T, Rülicke T, Brem G, Poulton J, Jones NS |date=June 2015 |title=Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism |journal=eLife |volume=4 |pages=e07464 |arxiv=1512.02988 |doi=10.7554/eLife.07464 |pmc=4486817 |pmid=26035426 |doi-access=free}}</ref>