ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2010
Lethal mutagenesis and evolutionary epidemiology.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Lethal mutagenesis and the transient within-host dynamics of viral adaptation.Virus evolution · 2025Article
- Mutators can drive the evolution of multi-resistance to antibiotics.PLoS genetics · 2023Article
- Evolution of Specialization in Heterogeneous Environments: Equilibrium Between Selection, Mutation and Migration.Genetics · 2020Article
- Mutational load causes stochastic evolutionary outcomes in acute RNA viral infection.Virus evolution · 2019Article
- Sixth European Seminar in Virology on Virus⁻Host Interaction at Single Cell and Organism Level.Viruses · 2018Article
- Two sides of the same coin: A population genetics perspective on lethal mutagenesis and mutational meltdown.Virus evolution · 2017Article
- The Nonstationary Dynamics of Fitness Distributions: Asexual Model with Epistasis and Standing Variation.Genetics · 2016Article
- New strategies against drug resistance to herpes simplex virus.International journal of oral science · 2016Review
- The Utility of Fisher's Geometric Model in Evolutionary Genetics.Annual review of ecology, evolution, and systematics · 2014Article
- What limits the evolutionary emergence of pathogens?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2013Article
- The probability of evolutionary rescue: towards a quantitative comparison between theory and evolution experiments.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2013Article
- Article
- A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918.Theoretical biology & medical modelling · 2012Article
- Interactions between evolutionary processes at high mutation rates.Evolution; international journal of organic evolution · 2012Article
- Mutation induced extinction in finite populations: lethal mutagenesis and lethal isolation.PLoS computational biology · 2012Article
- Article
- The effects of low-impact mutations in digital organisms.Theoretical biology & medical modelling · 2011Article
- New experimental and theoretical approaches towards the understanding of the emergence of viral infections. Introduction.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2010Article
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2 authors.
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Abstract
The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical underpinnings of this process are still not clearly established. A few recent models sought to describe lethal mutagenesis but they often relied on restrictive assumptions. We extend this earlier work in two novel directions. First, we derive the dynamics of the genetic load in a multivariate Gaussian fitness landscape akin to classical quantitative genetics models. This fitness landscape yields a continuous distribution of mutation effects on fitness, ranging from deleterious to beneficial (i.e. compensatory) mutations. We also include an additional class of lethal mutations. Second, we couple this evolutionary model with an epidemiological model accounting for the within-host dynamics of the pathogen. We derive the epidemiological and evolutionary equilibrium of the system. At this equilibrium, the density of the pathogen is expected to decrease linearly with the genomic mutation rate U. We also provide a simple expression for the critical mutation rate leading to extinction. Stochastic simulations show that these predictions are accurate for a broad range of parameter values. As they depend on a small set of measurable epidemiological and evolutionary parameters, we used available information on several viruses to make quantitative and testable predictions on critical mutation rates. In the light of this model, we discuss the feasibility of lethal mutagenesis as an efficient therapeutic strategy.
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