@article {Rotem2018Jun, title = {Evolution on the biophysical fitness landscape of an RNA virus}, journal = {Mol. Biol. Evol.}, volume = {35}, number = {10}, year = {2018}, month = {Jun}, pages = {2390{\textendash}2400}, 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. }, issn = {0737-4038}, doi = {10.1093/molbev/msy131}, url = {https://academic.oup.com/mbe/advance-article/doi/10.1093/molbev/msy131/5046249}, author = {Rotem, Assaf and Serohijos, Adrian W. R. and Chang, Connie B. and Wolfe, Joshua T. and Fischer, Audrey E. and Mehoke, Thomas S. and Zhang, Huidan and Tao, Ye and Ung, W. Lloyd and Choi, Jeong-Mo and Rodrigues, Jo{\i}fmmode\tildea\else{\~a}\fi}o V. and Abimbola, O. Kolawole and Koehler, Stephan A. and Wu, Susan and Thielen, Peter M. and Cui, Naiwen and Demirev, Plamen A. and Giacobbi, Nicholas S. and Julian, Timothy R. and Schwab, Kellogg and Lin, Jeffrey S. and Smith, Thomas J. and Pipas, James M. and Wobus, Christiane E. and Feldman, Andrew B. and Weitz, DavidA. and Shakhnovich, Eugene I.} }