Evolution on the Biophysical Fitness Landscape of an RNA Virus
| Autor: | Thomas J. Smith, Peter Thielen, Naiwen Cui, Adrian W.R. Serohijos, Nicholas S. Giacobbi, James M. Pipas, Jeffrey S. Lin, Susan Wu, Jeong-Mo Choi, Thomas Mehoke, Hua Zhang, David A. Weitz, Lloyd W. Ung, Ye Tao, Audrey Fischer, João V. Rodrigues, Joshua T. Wolfe, Andrew B. Feldman, Eugene I. Shakhnovich, Abimbola O. Kolawole, Connie B. Chang, Stephan A. Koehler, Plamen A. Demirev, Kellogg J. Schwab, Timothy R. Julian, Assaf Rotem, Christiane E. Wobus |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Folding fitness landscape Fitness landscape viruses Genetic Fitness Antibody Affinity microfluidics Biology 03 medical and health sciences Mice viral evolution Genetics Animals Selection Genetic Molecular Biology Ecology Evolution Behavior and Systematics Selection (genetic algorithm) Discoveries lab evolution Experimental evolution Models Genetic Protein Stability Fitness model Norovirus neutralizing antibody Epistasis Genetic folding stability Antibodies Neutralizing Biological Evolution Folding (chemistry) 030104 developmental biology Evolutionary biology Viral evolution Epistasis Capsid Proteins |
| Zdroj: | Molecular Biology and Evolution |
| ISSN: | 1537-1719 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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