Résumé
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.