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Beneficial mutation-selection dynamics in finite asexual populations: a free boundary approach.

ABSTRACT: Using a free boundary approach based on an analogy with ice melting models, we propose a deterministic PDE framework to describe the dynamics of fitness distributions in the presence of beneficial mutations with non-epistatic effects on fitness. Contrarily to most approaches based on deterministic models, our framework does not rely on an infinite population size assumption, and successfully captures the transient as well as the long time dynamics of fitness distributions. In particular, consistently with stochastic individual-based approaches or stochastic PDE approaches, it leads to a constant asymptotic rate of adaptation at large times, that most deterministic approaches failed to describe. We derive analytic formulas for the asymptotic rate of adaptation and the full asymptotic distribution of fitness. These formulas depend explicitly on the population size, and are shown to be accurate for a wide range of population sizes and mutation rates, compared to individual-based simulations. Although we were not able to derive an analytic description for the transient dynamics, numerical computations lead to accurate predictions and are computationally efficient compared to stochastic simulations. These computations show that the fitness distribution converges towards a travelling wave with constant speed, and whose profile can be computed analytically.

SUBMITTER: Roques L

PROVIDER: S-EPMC5736637 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Beneficial mutation-selection dynamics in finite asexual populations: a free boundary approach.

Roques Lionel L Garnier Jimmy J Martin Guillaume G

Scientific reports 20171219 1

Using a free boundary approach based on an analogy with ice melting models, we propose a deterministic PDE framework to describe the dynamics of fitness distributions in the presence of beneficial mutations with non-epistatic effects on fitness. Contrarily to most approaches based on deterministic models, our framework does not rely on an infinite population size assumption, and successfully captures the transient as well as the long time dynamics of fitness distributions. In particular, consist ...[more]

PMID: 29259180

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Project description:Reproduction is inherently risky, in part because genomic replication can introduce new mutations that are usually deleterious toward fitness. This risk is especially severe for organisms whose genomes replicate "semi-conservatively," e.g. viruses and bacteria, where no master copy of the genome is preserved. Lethal mutagenesis refers to extinction of populations due to an unbearably high mutation rate (U), and is important both theoretically and clinically, where drugs can extinguish pathogens by increasing their mutation rate. Previous theoretical models of lethal mutagenesis assume infinite population size (N). However, in addition to high U, small N can accelerate extinction by strengthening genetic drift and relaxing selection. Here, we examine how the time until extinction depends jointly on N and U. We first analytically compute the mean time until extinction (τ) in a simplistic model where all mutations are either lethal or neutral. The solution motivates the definition of two distinct regimes: a survival phase and an extinction phase, which differ dramatically in both how τ scales with N and in the coefficient of variation in time until extinction. Next, we perform stochastic population-genetics simulations on a realistic fitness landscape that both (i) features an epistatic distribution of fitness effects that agrees with experimental data on viruses and (ii) is based on the biophysics of protein folding. More specifically, we assume that mutations inflict fitness penalties proportional to the extent that they unfold proteins. We find that decreasing N can cause phase transition-like behavior from survival to extinction, which motivates the concept of "lethal isolation." Furthermore, we find that lethal mutagenesis and lethal isolation interact synergistically, which may have clinical implications for treating infections. Broadly, we conclude that stably folded proteins are only possible in ecological settings that support sufficiently large populations.

Dataset Information

Beneficial mutation-selection dynamics in finite asexual populations: a free boundary approach.

Publications

Beneficial mutation-selection dynamics in finite asexual populations: a free boundary approach.

Similar Datasets

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