ArticleNucleic acids research2021
A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Temporal control of mitochondrial mutagenesis reveals the fate of mtDNA mutations with age.bioRxiv : the preprint server for biology · 2026Article
- Article
- Sensitivity of genome-wide tests for mitonuclear genetic incompatibilities.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Article
- Mitochondrial Gene Phylogenetic Incongruencies Are Linked to Chromosomal Position and Function.Genome biology and evolution · 2025Article
- Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.World journal of methodology · 2025Review
- Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations.Science advances · 2025Article
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
- Disruption of recombination machinery alters the mutational landscape in plant organellar genomes.G3 (Bethesda, Md.) · 2025Article
- Deciphering the Foundations of Mitochondrial Mutational Spectra: Replication-Driven and Damage-Induced Signatures Across Chordate Classes.Molecular biology and evolution · 2025Article
- Maintaining mitochondrial DNA copy number mitigates ROS-induced oocyte decline and female reproductive aging.Communications biology · 2024Article
- Characterization and trans-generation dynamics of mitogene pool in the silver carp (Hypophthalmichthys molitrix).G3 (Bethesda, Md.) · 2024Article
- Mitochondrial DNA mosaicism in normal human somatic cells.Nature genetics · 2024Article
- NeMu: a comprehensive pipeline for accurate reconstruction of neutral mutation spectra from evolutionary data.Nucleic acids research · 2024Article
- Disruption of recombination machinery alters the mutational landscape in plant organellar genomes.bioRxiv : the preprint server for biology · 2024Article
- Article
- Frequencies and spectra of aflatoxin BNAR molecular medicine · 2024Article
- Mitochondrial Targeted Interventions for Aging.Cold Spring Harbor perspectives in medicine · 2024Review
- Investigating low frequency somatic mutations inbioRxiv : the preprint server for biology · 2024Article
- The Fate of Oxidative Strand Breaks in Mitochondrial DNA.Antioxidants (Basel, Switzerland) · 2023Article
- Secondary structure of the human mitochondrial genome affects formation of deletions.BMC biology · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in mitochondrial DNA (mtDNA) cause maternally inherited diseases, while somatic mutations are linked to common diseases of aging. Although mtDNA mutations impact health, the processes that give rise to them are under considerable debate. To investigate the mechanism by which de novo mutations arise, we analyzed the distribution of naturally occurring somatic mutations across the mouse and human mtDNA obtained by Duplex Sequencing. We observe distinct mutational gradients in G→A and T→C transitions delimited by the light-strand origin and the mitochondrial Control Region (mCR). The gradient increases unequally across the mtDNA with age and is lost in the absence of DNA polymerase γ proofreading activity. In addition, high-resolution analysis of the mCR shows that important regulatory elements exhibit considerable variability in mutation frequency, consistent with them being mutational 'hot-spots' or 'cold-spots'. Collectively, these patterns support genome replication via a deamination prone asymmetric strand-displacement mechanism as the fundamental driver of mutagenesis in mammalian DNA. Moreover, the distribution of mtDNA single nucleotide polymorphisms in humans and the distribution of bases in the mtDNA across vertebrate species mirror this gradient, indicating that replication-linked mutations are likely the primary source of inherited polymorphisms that, over evolutionary timescales, influences genome composition during speciation.
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