Affiliation:
1. Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
2. VIB Laboratory for Genetics and Genomics, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
3. Smart Systems and Emerging Technologies Unit, Imec (Interuniversity Micro-Electronics Centre), Leuven, Belgium
Abstract
While specific mutations allow organisms to adapt to stressful environments, most changes in an organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in cellular mutation rates as a response to changes in selective pressure. We show that hypermutation independently evolves when different Escherichia coli cultures adapt to high ethanol stress. Furthermore, hypermutator states are transitory and repeatedly alternate with decreases in mutation rate. Specifically, population mutation rates rise when cells experience higher stress and decline again once cells are adapted. Interestingly, we identified cellular mortality as the major force driving the quick evolution of mutation rates. Together, these findings show how organisms balance robustness and evolvability and help explain the prevalence of hypermutation in various settings, ranging from emergence of antibiotic resistance in microbes to cancer relapses upon chemotherapy.
Funder
Agentschap voor Innovatie door Wetenschap en Technologie
Fonds Wetenschappelijk Onderzoek
Onderzoeksraad, KU Leuven
H2020 European Research Council
Human Frontier Science Program
Vlaams Instituut voor Biotechnologie
European Molecular Biology Organization
Federaal Wetenschapsbeleid
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
89 articles.
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