The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells

Cao, Liqin; Shitara, Hiroshi; Horii, Takuro; Nagao, Yoshimi; Imai, Hiroshi; Abe, Kuniya; Hara, Takahiko; Hayashi, Jun‐Ichi; Yonekawa, Hiromichi

doi:10.1038/ng1970

Cited by 299 publications

(319 citation statements)

References 28 publications

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“…As for mammalian embryogenesis (Cao et al, 2007), the mtDNA content of teleost oocytes is believed to remain constant during early embryogenesis, and mitochondria present in the oocyte are apportioned to the cells of the developing embryo with the majority assigned to extraembryonic tissues (Fleming et al, 1992;Dumollard et al, 2007a). Thus, a genetic bottleneck comparable to that described for mammalian embryogenesis is expected in teleosts.…”

Section: Discussionmentioning

confidence: 98%

“…However, this ratio does not necessarily reflect the extent of paternal leakage in the developing embryo. The mtDNA content remains constant during early embryogenesis (Cao et al, 2007;Cree et al, 2008) and mitochondria are apportioned to arising cells in a random fashion. Because most of these cells form extraembryonic tissues (Hogan et al, 1986), only a subset of all cells and consequently mtDNAs present in the zygote will ultimately contribute to the embryo proper (Fleming et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Lost in the zygote: the dilution of paternal mtDNA upon fertilization

Wolff¹,

Gemmell²

2008

Heredity

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The mechanisms by which paternal inheritance of mitochondrial DNA (mtDNA) (paternal leakage) and, subsequently, recombination of mtDNA are prevented vary in a speciesspecific manner with one mechanism in common: paternally derived mtDNA is assumed to be vastly outnumbered by maternal mtDNA in the zygote. To date, this dilution effect has only been described for two mammalian species, human and mouse. Here, we estimate the mtDNA content of chinook salmon oocytes to evaluate the dilution effect operating in another vertebrate; the first such study outside a mammalian system. Employing real-time PCR, we determined the mtDNA content of chinook salmon oocytes to be 3.2 Â 10 9 ± 1.0 Â 10 9 , and recently, we determined the mtDNA content of chinook salmon sperm to be 5.73 ± 2.28 per gamete. Accordingly, the ratio of paternal-to-maternal mtDNA if paternal leakage occurs is estimated to be 1:5.5 Â 10 8 . This contribution of paternal mtDNA to the overall mtDNA pool in salmon zygotes is three to five orders of magnitude smaller than those revealed for the mammalian system, strongly suggesting that paternal inheritance of mtDNA per offspring will be much less likely in this system than in mammals.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Lost in the zygote: the dilution of paternal mtDNA upon fertilization

Wolff¹,

Gemmell²

2008

Heredity

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“…However, the vast majority of sexually reproducing organisms have uniparental transmission of mtDNA [8,44], maintaining high relatedness. Furthermore, regular single-celled bottlenecks, usually in combination with an additional bottleneck for mtDNA [9,10], facilitate efficient selection against suppressive mtDNA.…”

Section: (D) Mtdna Evolution In Other Organismsmentioning

confidence: 99%

“…Furthermore, an mtDNA bottleneck during egg cell formation has been shown in mice [9][10][11], redistributing mtDNA variation from within cells to among cells, and facilitating selection among individuals [12], as well as purifying selection in the germline [13]. A unifying characteristic of these different mechanisms is that they increase the genetic relatedness among the mtDNAs within individuals.…”

Section: Introductionmentioning

confidence: 99%

Regular bottlenecks and restrictions to somatic fusion prevent the accumulation of mitochondrial defects inNeurospora

Bastiaans

Aanen

Debets

et al. 2014

Phil. Trans. R. Soc. B

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The replication and segregation of multi-copy mitochondrial DNA (mtDNA) are not under strict control of the nuclear DNA. Within-cell selection may thus favour variants with an intracellular selective advantage but a detrimental effect on cell fitness. High relatedness among the mtDNA variants of an individual is predicted to disfavour such deleterious selfish genetic elements, but experimental evidence for this hypothesis is scarce. We studied the effect of mtDNA relatedness on the opportunities for suppressive mtDNA variants in the fungus Neurospora carrying the mitochondrial mutator plasmid pKALILO. During growth, this plasmid integrates into the mitochondrial genome, generating suppressive mtDNA variants. These mtDNA variants gradually replace the wild-type mtDNA, ultimately culminating in growth arrest and death. We show that regular sequestration of mtDNA variation is required for effective selection against suppressive mtDNA variants. First, bottlenecks in the number of mtDNA copies from which a ‘ Kalilo ’ culture started significantly increased the maximum lifespan and variation in lifespan among cultures. Second, restrictions to somatic fusion among fungal individuals, either by using anastomosis-deficient mutants or by generating allotype diversity, prevented the accumulation of suppressive mtDNA variants. We discuss the implications of these results for the somatic accumulation of mitochondrial defects during ageing.

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“…The number of mitochondria in an oocyte can be estimated by analysis of mtDNA copy number because oocytes contain only one to two mtDNA copies per mitochondrion (Pikó and Matsumoto 1976;Pikó and Taylor 1987;Jansen 2000;Santos et al 2006b;Jiao et al 2007;Chiaratti and Meirelles 2010). For successful early embryonic development, a species-specific minimum number of mitochondria appears to be required; for example, mouse oocytes are thought to require at least 50 000-200 000 mtDNA copies (Cao et al 2007;Cree et al 2008;Wai et al 2008Wai et al , 2010, whereas bovine, porcine and human oocytes have been reported to require between 100 000 and 700 000 mtDNA copies if they are to retain developmental competence (Steuerwald et al 2000;Reynier et al 2001;May-Panloup et al 2005a;Almeida-Santos et al 2006b;Spikings et al 2007;Zeng et al 2007). However, during early embryonic development, mtDNA replication is transiently arrested (St. John et al 2010) and therefore the mtDNA copy number either remains constant (e.g.…”

Section: Introductionmentioning

confidence: 99%

Maternal age and in vitro culture affect mitochondrial number and function in equine oocytes and embryos

Hendriks¹,

Colleoni²,

Galli³

et al. 2015

Reprod. Fertil. Dev.

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Abstract. Advanced maternal age and in vitro embryo production (IVP) predispose to pregnancy loss in horses. We investigated whether mare age and IVP were associated with alterations in mitochondrial (mt) DNA copy number or function that could compromise oocyte and embryo development. Effects of mare age (,12 vs $12 years) on mtDNA copy number, ATP content and expression of genes involved in mitochondrial replication (mitochondrial transcription factor (TFAM ), mtDNA polymerase g subunit B (mtPOLB) and mitochondrial single-stranded DNA-binding protein (SSB)), energy production (ATP synthase-coupling factor 6, mitochondrial-like (ATP-synth_F6)) and oxygen free radical scavenging (glutathione peroxidase 3 (GPX3)) were investigated in oocytes before and after in vitro maturation (IVM), and in early embryos. Expression of TFAM, mtPOLB and ATP-synth-F6 declined after IVM (P , 0.05). However, maternal age did not affect oocyte ATP content or expression of genes involved in mitochondrial replication or function. Day 7 embryos from mares $12 years had fewer mtDNA copies (P ¼ 0.01) and lower mtDNA : total DNA ratios (P , 0.01) than embryos from younger mares, indicating an effect not simply due to lower cell number. Day 8 IVP embryos had similar mtDNA copy numbers to Day 7 in vivo embryos, but higher mtPOLB (P ¼ 0.013) and a tendency to reduced GPX3 expression (P ¼ 0.09). The lower mtDNA number in embryos from older mares may compromise development, but could be an effect rather than cause of developmental retardation. The general down-regulation of genes involved in mitochondrial replication and function after IVM may compromise resulting embryos.

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The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells

Cited by 299 publications

References 28 publications

Lost in the zygote: the dilution of paternal mtDNA upon fertilization

Lost in the zygote: the dilution of paternal mtDNA upon fertilization

Regular bottlenecks and restrictions to somatic fusion prevent the accumulation of mitochondrial defects inNeurospora

Maternal age and in vitro culture affect mitochondrial number and function in equine oocytes and embryos

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