The extinction time under mutational meltdown driven by high mutation rates.

Lansch-Justen, Lucy; Cusseddu, Davide; Schmitz, Mark A; Bank, Claudia (2022). The extinction time under mutational meltdown driven by high mutation rates. Ecology and evolution, 12(7), e9046. John Wiley & Sons, Inc. 10.1002/ece3.9046

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Mutational meltdown describes an eco-evolutionary process in which the accumulation of deleterious mutations causes a fitness decline that eventually leads to the extinction of a population. Possible applications of this concept include medical treatment of RNA virus infections based on mutagenic drugs that increase the mutation rate of the pathogen. To determine the usefulness and expected success of such an antiviral treatment, estimates of the expected time to mutational meltdown are necessary. Here, we compute the extinction time of a population under high mutation rates, using both analytical approaches and stochastic simulations. Extinction is the result of three consecutive processes: (a) initial accumulation of deleterious mutations due to the increased mutation pressure; (b) consecutive loss of the fittest haplotype due to Muller's ratchet; (c) rapid population decline toward extinction. We find accurate analytical results for the mean extinction time, which show that the deleterious mutation rate has the strongest effect on the extinction time. We confirm that intermediate-sized deleterious selection coefficients minimize the extinction time. Finally, our simulations show that the variation in extinction time, given a set of parameters, is surprisingly small.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Ecology and Evolution (IEE)

UniBE Contributor:

Bank, Claudia

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

2045-7758

Publisher:

John Wiley & Sons, Inc.

Language:

English

Submitter:

Pubmed Import

Date Deposited:

12 Jul 2022 13:23

Last Modified:

05 Dec 2022 16:21

Publisher DOI:

10.1002/ece3.9046

PubMed ID:

35813923

Uncontrolled Keywords:

evolutionary theory extinction lethal mutagenesis mutagenic drugs mutational meltdown

BORIS DOI:

10.48350/171262

URI:

https://boris.unibe.ch/id/eprint/171262

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