Interpreting the Dependence of Mutation Rates on Age and Time.

Abstract:

:Mutations can originate from the chance misincorporation of nucleotides during DNA replication or from DNA lesions that arise between replication cycles and are not repaired correctly. We introduce a model that relates the source of mutations to their accumulation with cell divisions, providing a framework for understanding how mutation rates depend on sex, age, and cell division rate. We show that the accrual of mutations should track cell divisions not only when mutations are replicative in origin but also when they are non-replicative and repaired efficiently. One implication is that observations from diverse fields that to date have been interpreted as pointing to a replicative origin of most mutations could instead reflect the accumulation of mutations arising from endogenous reactions or exogenous mutagens. We further find that only mutations that arise from inefficiently repaired lesions will accrue according to absolute time; thus, unless life history traits co-vary, the phylogenetic "molecular clock" should not be expected to run steadily across species.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Gao Z,Wyman MJ,Sella G,Przeworski M

doi

10.1371/journal.pbio.1002355

subject

Has Abstract

pub_date

2016-01-13 00:00:00

pages

e1002355

issue

1

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-15-02541

journal_volume

14

pub_type

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