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A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus.

ABSTRACT: Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3DG64S, has a significant replication defect and that wild-type (WT) and 3DG64S populations have similar adaptability in 2 distinct cellular environments. Experimental evolution of 3DG64S under selection for replicative speed led to reversion and compensation of the fidelity phenotype. Mice infected with 3DG64S exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3DG64S growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity.

SUBMITTER: Fitzsimmons WJ

PROVIDER: S-EPMC6040757 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus.

Fitzsimmons William J WJ Woods Robert J RJ McCrone John T JT Woodman Andrew A Arnold Jamie J JJ Yennawar Madhumita M Evans Richard R Cameron Craig E CE Lauring Adam S AS

PLoS biology 20180628 6

Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has ...[more]

PMID: 29953453

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Project description:Many species are shifting their ranges in response to global climate change. Range expansions are known to have profound effects on the genetic composition of populations. The evolution of dispersal during range expansion increases invasion speed, provided that a species can adapt sufficiently fast to novel local conditions. Genetic diversity at the expanding range border is however depleted due to iterated founder effects. The surprising ability of colonizing species to adapt to novel conditions while being subjected to genetic bottlenecks is termed 'the genetic paradox of invasive species'. Mutational processes have been argued to provide an explanation for this paradox. Mutation rates can evolve, under conditions that favor an increased rate of adaptation, by hitchhiking on beneficial mutations through induced linkage disequilibrium. Here we argue that spatial sorting, iterated founder events, and population structure benefit the build-up and maintenance of such linkage disequilibrium. We investigate if the evolution of mutation rates could play a role in explaining the 'genetic paradox of invasive species' for a sexually reproducing species colonizing a landscape of gradually changing conditions.We use an individual-based model to show the evolutionary increase of mutation rates in sexual populations during range expansion, in coevolution with the dispersal probability. The observed evolution of mutation rate is adaptive and clearly advances invasion speed both through its effect on the evolution of dispersal probability, and the evolution of local adaptation. This also occurs under a variable temperature gradient, and under the assumption of 90% lethal mutations.In this study we show novel consequences of the particular genetic properties of populations under spatial disequilibrium, i.e. the coevolution of dispersal probability and mutation rate, even in a sexual species and under realistic spatial gradients, resulting in faster invasions. The evolution of mutation rates can therefore be added to the list of possible explanations for the 'genetic paradox of invasive species'. We conclude that range expansions and the evolution of mutation rates are in a positive feedback loop, with possibly far-reaching ecological consequences concerning invasiveness and the adaptability of species to novel environmental conditions.

Dataset Information

A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus.

Publications

A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus.

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