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Lookup NU author(s): Dr Axel Kowald, Emeritus Professor Thomas Kirkwood
Mitochondrial DNA deletions accumulate over the life course in post-mitotic cells of many species and may contribute to aging. Often a single mutant expands clonally and finally replaces the wild-type population of a whole cell. One proposal to explain the driving force behind this accumulation states that random drift alone, without any selection advantage, is sufficient to explain the clonal accumulation of a single mutant. Existing mathematical models show that such a process might indeed work for humans. However, to be a general explanation for the clonal accumulation of mtDNA mutants, it is important to know whether random drift could also explain the accumulation process in short-lived species like rodents. To clarify this issue, we modelled this process mathematically and performed extensive computer simulations to study how different mutation rates affect accumulation time and the resulting degree of heteroplasmy. We show that random drift works for lifespans of around 100years, but for short-lived animals, the resulting degree of heteroplasmy is incompatible with experimental observations.
Author(s): Kowald A, Kirkwood TBL
Publication type: Article
Publication status: Published
Journal: Aging Cell
Year: 2013
Volume: 12
Issue: 4
Pages: 728-731
Print publication date: 01/08/2013
Online publication date: 07/06/2013
Acceptance date: 10/05/2013
Date deposited: 04/11/2014
ISSN (print): 1474-9718
ISSN (electronic): 1474-9726
Publisher: Wiley-Blackwell
URL: http://dx.doi.org/10.1111/acel.12098
DOI: 10.1111/acel.12098
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