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Sci Adv. 2018 Jun 20;4(6):eaat1608. doi: 10.1126/sciadv.aat1608. eCollection 2018 Jun.

Heterogeneity of spontaneous DNA replication errors in single isogenic Escherichia coli cells.

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INSERM U1001, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
Centre National de la Recherche Scientifique, 75016 Paris, France.


Despite extensive knowledge of the molecular mechanisms that control mutagenesis, it is not known how spontaneous mutations are produced in cells with fully operative mutation-prevention systems. By using a mutation assay that allows visualization of DNA replication errors and stress response transcriptional reporters, we examined populations of isogenic Escherichia coli cells growing under optimal conditions without exogenous stress. We found that spontaneous DNA replication errors in proliferating cells arose more frequently in subpopulations experiencing endogenous stresses, such as problems with proteostasis, genome maintenance, and reactive oxidative species production. The presence of these subpopulations of phenotypic mutators is not expected to affect the average mutation frequency or to reduce the mean population fitness in a stable environment. However, these subpopulations can contribute to overall population adaptability in fluctuating environments by serving as a reservoir of increased genetic variability.

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