RT Journal Article
SR Electronic
T1 Population persistence under high mutation rate: from evolutionary rescue to lethal mutagenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 521203
DO 10.1101/521203
A1 Yoann Anciaux
A1 Amaury Lambert
A1 Ophélie Ronce
A1 Lionel Roques
A1 Guillaume Martin
YR 2019
UL http://biorxiv.org/content/early/2019/01/17/521203.abstract
AB 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 contributionsY.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.