ArticleProceedings of the National Academy of Sciences of the United States of America2022
Stochastic survival of the densest and mitochondrial DNA clonal expansion in aging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed.
- Review
- Optimal Organelle Inheritance Strategies Under Different Changing Environments and Mutational Pressures.Genome biology and evolution · 2026Article
- Article
- The mitogenome mutation repertoire affects progression of Parkinson's Disease.Genetics and molecular biology · 2026Article
- Cryptic mitochondrial DNA mutations coincide with mid-late life and are pathophysiologically informative in single cells across tissues and species.Nature communications · 2025Article
- Age-induced changes in skeletal muscle mitochondrial DNA synthesis, quantity, and quality in genetically unique rats.GeroScience · 2025Article
- 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
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Avoiding misleading estimates using mtDNA heteroplasmy statistics to study bottleneck size and selection.G3 (Bethesda, Md.) · 2023Article
- Mitochondrial network structure controls cell-to-cell mtDNA variability generated by cell divisions.PLoS computational biology · 2023Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expansion of mitochondrial DNA molecules with deletions has been associated with aging, particularly in skeletal muscle fibers; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage (RA) to mitochondrial DNA containing deletion mutations, but there is also evidence that cells can selectively remove defective mitochondrial DNA. Here we present a spatial model that, without an RA, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data. A standard model based on RA yields waves that are too fast. We provide a formula that predicts that wave speed drops with copy number, consonant with experimental data. Crucially, our model yields traveling waves of mutants even if mutants are preferentially eliminated. Additionally, we predict that mutant loads observed in single-cell experiments can be produced by de novo mutation rates that are drastically lower than previously thought for neutral models. Given this exemplar of how spatial structure (multiple linked mtDNA populations), noise, and density affect muscle cell aging, we introduce the mechanism of stochastic survival of the densest (SSD), an alternative to RA, that may underpin other evolutionary phenomena.
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