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 Bioljournal_title
PLoS biologyauthors
Gao Z,Wyman MJ,Sella G,Przeworski Mdoi
10.1371/journal.pbio.1002355subject
Has Abstractpub_date
2016-01-13 00:00:00pages
e1002355issue
1eissn
1544-9173issn
1545-7885pii
PBIOLOGY-D-15-02541journal_volume
14pub_type
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