Evolution on the Biophysical Fitness Landscape of an RNA Virus

Assaf Rotem, Adrian W.R. Serohijos, Connie B. Chang, Joshua T. Wolfe, Audrey E. Fischer, Thomas S. Mehoke, Huidan Zhang, Ye Tao, W. Lloyd Ung, Jeong Mo Choi, João V. Rodrigues, Abimbola O. Kolawole, Stephan A. Koehler, Susan Wu, Peter M. Thielen, Naiwen Cui, Plamen A. Demirev, Nicholas S. Giacobbi, Timothy R. Julian, Kellogg Schwab & 7 others Jeffrey S. Lin, Thomas Smith, James M. Pipas, Christiane E. Wobus, Andrew B. Feldman, David A. Weitz, Eugene I. Shakhnovich

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2390-2400
Number of pages11
JournalMolecular Biology and Evolution
Volume35
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Norovirus
Antibody Affinity
Microfluidics
Capsid
RNA Viruses
Viral Proteins
Population Density
Neutralizing Antibodies
RNA
virus
fitness
Genotype
Mutation
antibody
folding
capsid
viral proteins
subpopulation
neutralizing antibodies
population size

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

Cite this

Rotem, A., Serohijos, A. W. R., Chang, C. B., Wolfe, J. T., Fischer, A. E., Mehoke, T. S., ... Shakhnovich, E. I. (2018). Evolution on the Biophysical Fitness Landscape of an RNA Virus. Molecular Biology and Evolution, 35(10), 2390-2400. https://doi.org/10.1093/molbev/msy131

Evolution on the Biophysical Fitness Landscape of an RNA Virus. / Rotem, Assaf; Serohijos, Adrian W.R.; Chang, Connie B.; Wolfe, Joshua T.; Fischer, Audrey E.; Mehoke, Thomas S.; Zhang, Huidan; Tao, Ye; Lloyd Ung, W.; Choi, Jeong Mo; Rodrigues, João V.; Kolawole, Abimbola O.; Koehler, Stephan A.; Wu, Susan; Thielen, Peter M.; Cui, Naiwen; Demirev, Plamen A.; Giacobbi, Nicholas S.; Julian, Timothy R.; Schwab, Kellogg; Lin, Jeffrey S.; Smith, Thomas; Pipas, James M.; Wobus, Christiane E.; Feldman, Andrew B.; Weitz, David A.; Shakhnovich, Eugene I.

In: Molecular Biology and Evolution, Vol. 35, No. 10, 01.10.2018, p. 2390-2400.

Research output: Contribution to journalArticle

Rotem, A, Serohijos, AWR, Chang, CB, Wolfe, JT, Fischer, AE, Mehoke, TS, Zhang, H, Tao, Y, Lloyd Ung, W, Choi, JM, Rodrigues, JV, Kolawole, AO, Koehler, SA, Wu, S, Thielen, PM, Cui, N, Demirev, PA, Giacobbi, NS, Julian, TR, Schwab, K, Lin, JS, Smith, T, Pipas, JM, Wobus, CE, Feldman, AB, Weitz, DA & Shakhnovich, EI 2018, 'Evolution on the Biophysical Fitness Landscape of an RNA Virus', Molecular Biology and Evolution, vol. 35, no. 10, pp. 2390-2400. https://doi.org/10.1093/molbev/msy131
Rotem A, Serohijos AWR, Chang CB, Wolfe JT, Fischer AE, Mehoke TS et al. Evolution on the Biophysical Fitness Landscape of an RNA Virus. Molecular Biology and Evolution. 2018 Oct 1;35(10):2390-2400. https://doi.org/10.1093/molbev/msy131
Rotem, Assaf ; Serohijos, Adrian W.R. ; Chang, Connie B. ; Wolfe, Joshua T. ; Fischer, Audrey E. ; Mehoke, Thomas S. ; Zhang, Huidan ; Tao, Ye ; Lloyd Ung, W. ; Choi, Jeong Mo ; Rodrigues, João V. ; Kolawole, Abimbola O. ; Koehler, Stephan A. ; Wu, Susan ; Thielen, Peter M. ; Cui, Naiwen ; Demirev, Plamen A. ; Giacobbi, Nicholas S. ; Julian, Timothy R. ; Schwab, Kellogg ; Lin, Jeffrey S. ; Smith, Thomas ; Pipas, James M. ; Wobus, Christiane E. ; Feldman, Andrew B. ; Weitz, David A. ; Shakhnovich, Eugene I. / Evolution on the Biophysical Fitness Landscape of an RNA Virus. In: Molecular Biology and Evolution. 2018 ; Vol. 35, No. 10. pp. 2390-2400.
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