Cited by 340Mitochondrial Function and PathologyEvolution and Genetic DynamicsForensic and Genetic Research

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Random Intracellular Drift Explains the Clonal Expansion of Mitochondrial DNA Mutations with Age

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Elson, J.L., Samuels, D.C., Turnbull, D.M., Chinnery, P.F.·2001·The American Journal of Human Genetics

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Abstract

Human tissues acquire somatic mitochondrial DNA (mtDNA) mutations with age. Very high levels of specific mtDNA mutations accumulate within individual cells, causing a defect of mitochondrial oxidative metabolism. This is a fundamental property of nondividing tissues, but it is not known how it comes about. To explore this problem, we developed a model of mtDNA replication within single human cells. Using this model, we show that relaxed replication of mtDNA alone can lead, through random genetic drift, to the clonal expansion of single mutant events during human life. Significant expansions primarily develop from mutations acquired during a critical period in childhood or early adult life.

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Authors: Elson, J. L., Samuels, D. C., Turnbull, D. M., & Chinnery, P. F.
Affiliations: Newcastle University (GB)
Corresponding author: Chinnery, P.F.
ORCID: Elson, J.L.
Samuels, D.C.
Turnbull, D.M.
Chinnery, P.F.
Venue: The American Journal of Human Genetics
Publisher: Elsevier BV
Published: 2001-03
Volume: 68
Issue: 3
Pages: 802-806
ISSN: 0002-9297 (ISSN-L)
DOI: 10.1086/318801
PMC: PMC1274494
OpenAlex: W2042734644
Cited by: 340
References: 31
Citations by year: 2026: 10 · 2025: 12 · 2024: 15 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 14 · 2019: 18 · 2018: 17 · 2017: 9 · 2016: 8 · 2015: 19 · 2014: 22 · 2013: 13 · 2012: 10
FWCI: 6.18
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4523 d)
Locations: The American Journal of Human Genetics (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords: mitochondrial DNA mutations, clonal expansion, somatic mutations, genetic drift, mitochondrial DNA replication, aging, oxidative metabolism, single-cell model, mutation accumulation
MeSH terms: Adult, Aging, Child, DNA Replication, DNA, Mitochondrial, Gene Frequency, Humans, Mitochondria, Models, Genetic, Mutation, Oxidative Phosphorylation, Probability, Founder Effect

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Random Intracellular Drift Explains the Clonal Expansion of Mitochondrial DNA Mutations with Age

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