Dataset Information

Evolution on the Biophysical Fitness Landscape of an RNA Virus.

ABSTRACT: Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics that propagates millions of independent small viral subpopulations. We demonstrate that along the axis of binding affinity, selection for escape variants and drift due to random mutations have the same direction, an atypical case in evolution. However, along folding stability, selection and drift are opposing forces whose balance is tuned by viral population size. Our results demonstrate that predictable epistatic tradeoffs between molecular traits of viral proteins shape viral evolution.

SUBMITTER: Rotem A

PROVIDER: S-EPMC6188569 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Evolution on the Biophysical Fitness Landscape of an RNA Virus.

Rotem Assaf A Serohijos Adrian W R AWR Chang Connie B CB Wolfe Joshua T JT Fischer Audrey E AE Mehoke Thomas S TS Zhang Huidan H Tao Ye Y Lloyd Ung W W Choi Jeong-Mo JM Rodrigues João V JV Kolawole Abimbola O AO Koehler Stephan A SA Wu Susan S Thielen Peter M PM Cui Naiwen N Demirev Plamen A PA Giacobbi Nicholas S NS Julian Timothy R TR Schwab Kellogg K Lin Jeffrey S JS Smith Thomas J TJ Pipas James M JM Wobus Christiane E CE Feldman Andrew B AB Weitz David A DA Shakhnovich Eugene I EI

Molecular biology and evolution 20181001 10

Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics t ...[more]

PMID: 29955873

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Project description:Adaptive fitness landscapes are a fundamental concept in evolutionary biology that relate the genotypes of individuals to their fitness. In the end, the evolutionary fate of evolving populations depends on the topography of the landscape, that is, the numbers of accessible mutational pathways and possible fitness peaks (i.e., adaptive solutions). For a long time, fitness landscapes were only theoretical constructions due to a lack of precise information on the mapping between genotypes and phenotypes. In recent years, however, efforts have been devoted to characterizing the properties of empirical fitness landscapes for individual proteins or for microbes adapting to artificial environments. In a previous study, we characterized the properties of the empirical fitness landscape defined by the first five mutations fixed during adaptation of tobacco etch potyvirus (TEV) to a new experimental host, Arabidopsis thaliana Here we evaluate the topography of this landscape in the ancestral host Nicotiana tabacum By comparing the topographies of the landscapes for the two hosts, we found that some features remained similar, such as the existence of fitness holes and the prevalence of epistasis, including cases of sign and reciprocal sign epistasis that created rugged, uncorrelated, and highly random topographies. However, we also observed significant differences in the fine-grained details between the two landscapes due to changes in the fitness and epistatic interactions of some genotypes. Our results support the idea that not only fitness tradeoffs between hosts but also topographical incongruences among fitness landscapes in alternative hosts may contribute to virus specialization. IMPORTANCE Despite its importance for understanding virus evolutionary dynamics, very little is known about the topography of virus adaptive fitness landscapes, and even less is known about the effects that different host species and environmental conditions may have on this topography. To bridge this gap, we evaluated the topography of a small fitness landscape formed by all genotypes that result from every possible combination of the first five mutations fixed during adaptation of TEV to the novel host A. thaliana To assess the effect that host species may have on this topography, we evaluated the fitness of every genotype in both the ancestral and novel hosts. We found that both landscapes share some macroscopic properties, such as the existence of holes and being highly rugged and uncorrelated, yet they differ in microscopic details due to changes in the magnitude and sign of fitness and epistatic effects.

Dataset Information

Evolution on the Biophysical Fitness Landscape of an RNA Virus.

Publications

Evolution on the Biophysical Fitness Landscape of an RNA Virus.

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