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Mol Cell. 2019 Aug 8;75(3):421-425. doi: 10.1016/j.molcel.2019.06.029.

Mutation Rate Heterogeneity Increases Odds of Survival in Unpredictable Environments.

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Department of Infection, Immunity, and Inflammation, Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, 75014 Paris, France. Electronic address:


Mutation rates affect both a population's present fitness and its capacity to adapt to future environmental changes. When the available genetic variability limits adaptation to environmental change, natural selection favors high mutations rates. However, constitutively high mutation rates compromise the fitness of a population in stable environments. This problem may be resolved if an increase in mutation rates is limited to times of stress, restricted to some genomic regions, and occurs only in a subpopulation of cells. Such within-population heterogeneity of mutation rates can result from genetic, environmental, and stochastic effects. The presence of subpopulations of transient mutator cells does not jeopardize the overall fitness of a population under stable environmental conditions. However, they can increase the odds of survival in changing environments because they represent reservoirs of increased genetic variability. This article presents evidence that such heterogeneity of mutation rates is more the norm than the exception.


DNA repair; adaptation; antibiotics; cancer; microbial population; mutation rates; replication fidelity; stress

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