RT Journal Article SR Electronic T1 Heterogeneity of spontaneous DNA replication errors in single isogenic Escherichia coli cells JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaat1608 DO 10.1126/sciadv.aat1608 VO 4 IS 6 A1 Woo, Anthony C. A1 Faure, Louis A1 Dapa, Tanja A1 Matic, Ivan YR 2018 UL http://advances.sciencemag.org/content/4/6/eaat1608.abstract AB 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.