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Cited by 45Evolution and Genetic DynamicsBacterial Genetics and BiotechnologyFungal and yeast genetics research

Coupling phenotypic persistence to DNA damage increases genetic diversity in severe stress

Yaakov, Gilad, Lerner, David, Bentele, Kajetan, Steinberger, Joseph, Barkai, Naama·2017·Nature Ecology & Evolution
DOI 10.1038/s41559-016-0016
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Abstract

Mutation rate balances the need to protect genome integrity with the advantage of evolutionary innovations. Microorganisms increase their mutation rate when stressed, perhaps addressing the growing need for evolutionary innovation. Such a strategy, however, is only beneficial under moderate stresses that allow cells to divide and realize their mutagenic potential. In contrast, severe stresses rapidly kill the majority of the population with the exception of a small minority of cells that are in a phenotypically distinct state termed persistence. Although persisters were discovered many decades ago, the stochastic event triggering persistence is poorly understood. We report that spontaneous DNA damage triggers persistence in Saccharomyces cerevisiae by activating the general stress response, providing protection against a range of harsh stress and drug environments. We further show that the persister subpopulation carries an increased load of genetic variants in the form of insertions, deletions or large structural variations, which are unrelated to their stress survival. This coupling of DNA damage to phenotypic persistence may increase genetic diversity specifically in severe stress conditions, where diversity is beneficial but the ability to generate de novo mutations is limited.

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Crossref · 10.1038/s41559-016-0016

Cites

44 of 44 references verified0 citation errors · 0 not checkable

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  • Under stress conditions, cells with high expression of Hsp12 survived better than those with normal expression, suggesting that Hsp12 is a possible molecular marker of persistence.

    “Under stress conditions, cells with high expression of heat-shock protein 12 (Hsp12) survived better than those with normal expression, suggesting that Hsp12 is a possible molecular marker of persistence [45].”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [45]

  • Spontaneous DNA damage triggers persistence in S. cerevisiae by activating the general stress response, withstanding a series of environmental stress and drug pressure.

    “It has been found that spontaneous DNA damage triggers persistence in S. cerevisiae by activating the general stress response, withstanding a series of environmental stress and drug pressure.”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [45]

  • Hsp12 marked persisters in budding yeast, because of its high expression in cells that survive under extreme environmental stresses.

    “Moreover, this study also found that Hsp12 marked persisters in budding yeast, because of its high expression in cells that survive under extreme environmental stresses [45].”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [45]

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Authors
Yaakov, G., Lerner, D., Bentele, K., Steinberger, J., & Barkai, N.
Affiliations
Weizmann Institute of Science (IL)
Corresponding author
  • Yaakov, Gilad
  • Barkai, Naama
ORCID
Venue
Nature Ecology & Evolution
Publisher
Springer Science and Business Media LLC
Published
2017-01-04
Volume
1
Issue
1
Pages
1-8
ISSN
2397-334X (ISSN-L)
DOI
10.1038/s41559-016-0016
OpenAlex
W2568840014
Cited by
45
References
44
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 4
FWCI
4.89
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Nature Ecology & Evolution (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
persister cells, DNA damage, mutation rate, genetic diversity, general stress response, Saccharomyces cerevisiae, structural variants, indels, severe stress, adaptive evolution, stress tolerance

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