ArticleProceedings of the National Academy of Sciences of the United States of America2015
Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed.
- Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients.Scientific reports · 2021Trial
- Variations in mitochondrial genome as potential prognostic markers in sickle cell disease.Haematologica · 2026Article
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- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- The Use of Single-Cell Mitochondrial DNA SNP Combinations for Distinguishing Organ-Specific Cell Types.Cells · 2026Article
- Mitochondrial genetic variation across tissues of the human body.Nucleic acids research · 2026Article
- Uncovering a Medieval Pogrom: Genetic History of a Jewish Community in Catalonia (Spain).Genes · 2026Article
- Clinical Validation of Digital PCR for Precise m.3243A>G Heteroplasmy Quantification in Early-Onset Diabetes.Journal of diabetes research · 2026Article
- Kidney mitochondrial DNA contributes to systemic IL-6 release in sepsis-associated acute kidney injury.JCI insight · 2025Article
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- Mitochondrial haplogroups, but not heteroplasmy, are associated with midlife cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations.Science advances · 2025Article
- Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging.Nature aging · 2025Article
- Selfish mutations promote age-associated erosion of mtDNA integrity in mammals.Nature communications · 2025Article
- First follicular fluid cf-mtDNA sequencing unveils ovarian stimulation-induced mutations impacting oocyte quality and IVF success.Journal of assisted reproduction and genetics · 2025Article
- Deleterious mitochondrial heteroplasmies exhibit increased longitudinal change in variant allele fraction.iScience · 2025Article
- Sequencing and characterizing human mitochondrial genomes in the biobank-based genomic research paradigm.Science China. Life sciences · 2025Review
- A Post-Mortem Molecular Damage Profile in the Ancient Human Mitochondrial DNA.Molecular ecology resources · 2025Article
- Tapping natures rhythm: the role of season in mitochondrial function and genetics in the UK biobank.Human genomics · 2025Article
82 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
Heteroplasmy in human mtDNA may play a role in cancer, other diseases, and aging, but patterns of heteroplasmy variation across different tissues have not been thoroughly investigated. Here, we analyzed complete mtDNA genome sequences at ∼3,500× average coverage from each of 12 tissues obtained at autopsy from each of 152 individuals. We identified 4,577 heteroplasmies (with an alternative allele frequency of at least 0.5%) at 393 positions across the mtDNA genome. Surprisingly, different nucleotide positions (nps) exhibit high frequencies of heteroplasmy in different tissues, and, moreover, heteroplasmy is strongly dependent on the specific consensus allele at an np. All of these tissue-related and allele-related heteroplasmies show a significant age-related accumulation, suggesting positive selection for specific alleles at specific positions in specific tissues. We also find a highly significant excess of liver-specific heteroplasmies involving nonsynonymous changes, most of which are predicted to have an impact on protein function. This apparent positive selection for reduced mitochondrial function in the liver may reflect selection to decrease damaging byproducts of liver mitochondrial metabolism (i.e., "survival of the slowest"). Overall, our results provide compelling evidence for positive selection acting on some somatic mtDNA mutations.
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