Back to Search Start Over

Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age.

Authors :
Elson JL
Samuels DC
Turnbull DM
Chinnery PF
Source :
American journal of human genetics [Am J Hum Genet] 2001 Mar; Vol. 68 (3), pp. 802-6. Date of Electronic Publication: 2001 Feb 06.
Publication Year :
2001

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.

Details

Language :
English
ISSN :
0002-9297
Volume :
68
Issue :
3
Database :
MEDLINE
Journal :
American journal of human genetics
Publication Type :
Academic Journal
Accession number :
11179029
Full Text :
https://doi.org/10.1086/318801