1. Microbiology and Infectious Disease
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Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli

Research Article
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Cite this article as: eLife 2017;6:e22939 doi: 10.7554/eLife.22939

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.

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Article and author information

Author details

  1. Toon Swings

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1225-3377
  2. Bram Van den Bergh

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  3. Sander Wuyts

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Eline Oeyen

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  5. Karin Voordeckers

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Kevin J Verstrepen

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  7. Maarten Fauvart

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  8. Natalie Verstraeten

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  9. Jan Michiels

    Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Leuven, Belgium
    For correspondence
    jan.michiels@kuleuven.be
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5829-0897

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.

Reviewing Editor

  1. Wenying Shou, Fred Hutchinson Cancer Research Center, United States

Publication history

  1. Received: November 3, 2016
  2. Accepted: April 18, 2017
  3. Accepted Manuscript published: May 2, 2017 (version 1)
  4. Version of Record published: May 12, 2017 (version 2)

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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