Population persistence under high mutation rate: From evolutionary rescue to lethal mutagenesis

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DOI

  • Yoann Anciaux
  • Amaury Lambert, Sorbonne Univ, Sorbonne Universite, LPSM, CNRS UMR 8001
  • ,
  • Ophelie Ronce, ISEM, Languedoc-Roussillon Universites (ComUE), Institut de Recherche pour le Developpement (IRD), Universite de Montpellier, Centre National de la Recherche Scientifique (CNRS), CNRS, France
  • Lionel Roques, BioSP, INRA
  • ,
  • Guillaume Martin, ISEM, Languedoc-Roussillon Universites (ComUE), Institut de Recherche pour le Developpement (IRD), Universite de Montpellier, Centre National de la Recherche Scientifique (CNRS), CNRS, France

Populations may genetically adapt to severe stress that would otherwise cause their extirpation. Recent theoretical work, combining stochastic demography with Fisher's geometric model of adaptation, has shown how evolutionary rescue becomes unlikely beyond some critical intensity of stress. Increasing mutation rates may however allow adaptation to more intense stress, raising concerns about the effectiveness of treatments against pathogens. This previous work assumes that populations are rescued by the rise of a single resistance mutation. However, even in asexual organisms, rescue can also stem from the accumulation of multiple mutations in a single genome. Here, we extend previous work to study the rescue process in an asexual population where the mutation rate is sufficiently high so that such events may be common. We predict both the ultimate extinction probability of the population and the distribution of extinction times. We compare the accuracy of different approximations covering a large range of mutation rates. Moderate increase in mutation rates favors evolutionary rescue. However, larger increase leads to extinction by the accumulation of a large mutation load, a process called lethal mutagenesis. We discuss how these results could help design "evolution-proof" antipathogen treatments that even highly mutable strains could not overcome.

Original languageEnglish
JournalEvolution
Volume73
Issue8
Pages (from-to)1517-1532
Number of pages16
ISSN0014-3820
DOIs
Publication statusPublished - 27 May 2019

    Research areas

  • Distribution of extinction times, evolutionary rescue, extinction dynamics, Fisher's geometric model, fitness landscape, lethal mutagenesis, NATURAL-SELECTION, DRUG-RESISTANCE, ADAPTATION, EXTINCTION, EPISTASIS, DISTRIBUTIONS, GENETICS, MODEL

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