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

View ORCID ProfileYoann Anciaux, View ORCID ProfileAmaury Lambert, Ophélie Ronce, View ORCID ProfileLionel Roques, View ORCID ProfileGuillaume Martin
doi: https://doi.org/10.1101/521203
Yoann Anciaux
1Bioinformatics Research Center (BiRC), Aarhus University, C.F. Møllers Allé 8, 8000 Aarhus Denmark
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Amaury Lambert
3Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France
4Laboratoire de Probabilités, Statistique et Modélisation (LPSM), Sorbonne Université, CNRS UMR 8001, Paris, France
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Ophélie Ronce
2Institut des Sciences de I’Evolution de Montpellier, Université de Montpellier, CNRS, IRD, EPHE, Montpellier, France
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Lionel Roques
5BioSP, INRA, 84914, Avignon, France
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Guillaume Martin
2Institut des Sciences de I’Evolution de Montpellier, Université de Montpellier, CNRS, IRD, EPHE, Montpellier, France
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Abstract

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 this model 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” anti-pathogen treatments that even highly mutable strains could not overcome.

Authors contributions

Y.A. O.R. and G.M. initiated the idea for the study. YA, A.L, L.R and G.M derived the mathematical results. Y.A. performed the simulations. Y.A. O.R. and G.M. drafted the paper. All authors critically revised the manuscript, and gave approval of the final version for submission.

Footnotes

  • Contact Information: yoann.anciaux{at}birc.au.dk

  • Conflict of Interest Statement: The authors declare no conflict of interests.

  • Data Accessibility Statement: The authors state that there is no data to be archived.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 17, 2019.
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Population persistence under high mutation rate: from evolutionary rescue to lethal mutagenesis
Yoann Anciaux, Amaury Lambert, Ophélie Ronce, Lionel Roques, Guillaume Martin
bioRxiv 521203; doi: https://doi.org/10.1101/521203
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Population persistence under high mutation rate: from evolutionary rescue to lethal mutagenesis
Yoann Anciaux, Amaury Lambert, Ophélie Ronce, Lionel Roques, Guillaume Martin
bioRxiv 521203; doi: https://doi.org/10.1101/521203

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