ArticleeLife2015
Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review and Developmental Perspective on Origin of CMS Genes in Crops.International journal of molecular sciences · 2024Pooled it
- Mitochondrial DNA Inheritance and Germline Purifying Selection: Insights FromAnnual review of genetics · 2026Review
- Optimal Organelle Inheritance Strategies Under Different Changing Environments and Mutational Pressures.Genome biology and evolution · 2026Article
- A modeller's guide for biomedical discovery.Disease models & mechanisms · 2026Article
- Single-molecule mitochondrial DNA imaging reveals heteroplasmy dynamics shaped by developmental bottlenecks and selection in vivo.Developmental cell · 2026Article
- The nuclear and mitochondrial genomes need to tango. How is their dance synchronized during development?NAR molecular medicine · 2026Article
- Age-related changes in mitochondrial markers and telomere dynamics during initial growth of human preantral follicles.Journal of assisted reproduction and genetics · 2026Article
- The bottleneck for maternal transmission of mtDNA is linked to purifying selection by autophagy.Science advances · 2025Article
- Evaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities.Annual review of genetics · 2025Review
- Mitochondrial curation for the next generation.Current opinion in genetics & development · 2025Review
- Real-time assessment of mitochondrial DNA heteroplasmy dynamics at the single-cell level.The EMBO journal · 2024Article
- Evolution and maintenance of mtDNA gene content across eukaryotes.The Biochemical journal · 2024Review
- Nanobiopsy investigation of the subcellular mtDNA heteroplasmy in human tissues.Scientific reports · 2024Article
- Stochastic organelle genome segregation through Arabidopsis development and reproduction.The New phytologist · 2024Article
- APOGEE 2: multi-layer machine-learning model for the interpretable prediction of mitochondrial missense variants.Nature communications · 2023Article
- The role of mtDNA in oocyte quality and embryo development.Molecular reproduction and development · 2023Review
- Avoiding misleading estimates using mtDNA heteroplasmy statistics to study bottleneck size and selection.G3 (Bethesda, Md.) · 2023Article
- Mitochondria in human reproduction: novel paradigm in the onset of neurodegenerative disorders.Physiological research · 2023Review
- Mitochondrial network structure controls cell-to-cell mtDNA variability generated by cell divisions.PLoS computational biology · 2023Article
- Mitochondrial Inheritance Following Nuclear Transfer: From Cloned Animals to Patients with Mitochondrial Disease.Methods in molecular biology (Clifton, N.J.) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability to address inherited mtDNA diseases. We produce a new, physically motivated, generalisable theoretical model for mtDNA populations during development, allowing the first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most statistical support for a combination of binomial partitioning of mtDNAs at cell divisions and random mtDNA turnover, meaning that the debated exact magnitude of mtDNA copy number depletion is flexible. New experimental measurements from a wild-derived mtDNA pairing in mice confirm the theoretical predictions of this model. We analytically solve a mathematical description of this mechanism, computing probabilities of mtDNA disease onset, efficacy of clinical sampling strategies, and effects of potential dynamic interventions, thus developing a quantitative and experimentally-supported stochastic theory of the bottleneck.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.