Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli
- KU Leuven - University of 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.
Data availability
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Highly ethanol tolerant Escherichia coli with hypermutation phenotypePublicly available at the NCBI SRA repository (Accession no: PRJNA344553).
Article and author information
Author details
Funding
Agentschap voor Innovatie door Wetenschap en Technologie (Strategic Basic Research Fellowship,121525)
- Toon Swings
Fonds Wetenschappelijk Onderzoek (Postdoctoral Fellowship,1249117N)
- Karin Voordeckers
Onderzoeksraad, KU Leuven (IDO/09/010)
- Kevin J Verstrepen
- Jan Michiels
Onderzoeksraad, KU Leuven (IDO/13/008)
- Jan Michiels
Onderzoeksraad, KU Leuven (CREA/13/019)
- Maarten Fauvart
Onderzoeksraad, KU Leuven (DBOF/12/035; DBOF/14/049)
- Kevin J Verstrepen
- Jan Michiels
Fonds Wetenschappelijk Onderzoek (KAN2014 1.5.222.14)
- Maarten Fauvart
Onderzoeksraad, KU Leuven (PF/10/010)
- Kevin J Verstrepen
- Jan Michiels
Interuniversity Attraction Poles-Belgian Science Policy Office (IAP P7/28)
- Jan Michiels
H2020 European Research Council (241426)
- Kevin J Verstrepen
Human Frontier Science Program (RGP0050/2013)
- Kevin J Verstrepen
Fonds Wetenschappelijk Onderzoek (G047112N)
- Jan Michiels
Vlaams Instituut voor Biotechnologie
- Kevin J Verstrepen
European Molecular Biology Organization
- Kevin J Verstrepen
Fonds Wetenschappelijk Onderzoek (Postdoctoral Fellowship,12O1917N)
- Bram Van den Bergh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Swings et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli
eLife 6:e22939.
https://doi.org/10.7554/eLife.22939
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