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

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...

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Bibliographic Details
Published in:American journal of human genetics 2001-03, Vol.68 (3), p.802-806
Main Authors: Elson, J.L., Samuels, D.C., Turnbull, D.M., Chinnery, P.F.
Format: Article
Language:English
Subjects:
Adult
Aging - genetics
Biological and medical sciences
Child
Development. Metamorphosis. Moult. Ageing
DNA Replication
DNA, Mitochondrial - genetics
Founder Effect
Fundamental and applied biological sciences. Psychology
Gene Frequency
Humans
Mitochondria - genetics
Mitochondria - metabolism
Models, Genetic
Mutation
Oxidative Phosphorylation
Probability
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1086/318801