Host heterogeneity and epistasis explain punctuated evolution of SARS-CoV-2

Bjarke Frost Nielsen, Chadi M. Saad-Roy, Yimei Li, Kim Sneppen, Lone Simonsen, Cécile Viboud, Simon A. Levin, Bryan T. Grenfell

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Identifying drivers of viral diversity is key to understanding the evolutionary as well as epidemiological dynamics of the COVID-19 pandemic. Using rich viral genomic data sets, we show that periods of steadily rising diversity have been punctuated by sudden, enormous increases followed by similarly abrupt collapses of diversity. We introduce a mechanistic model of saltational evolution with epistasis and demonstrate that these features parsimoniously account for the observed temporal dynamics of inter-genomic diversity. Our results provide support for recent proposals that saltational evolution may be a signature feature of SARS-CoV-2, allowing the pathogen to more readily evolve highly transmissible variants. These findings lend theoretical support to a heightened awareness of biological contexts where increased diversification may occur. They also underline the power of pathogen genomics and other surveillance streams in clarifying the phylodynamics of emerging and endemic infections. In public health terms, our results further underline the importance of equitable distribution of up-to-date vaccines.

Original languageEnglish (US)
Article numbere1010896
JournalPLoS computational biology
Issue number2
StatePublished - Feb 2023

All Science Journal Classification (ASJC) codes

  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Cellular and Molecular Neuroscience
  • Molecular Biology
  • Ecology
  • Computational Theory and Mathematics
  • Modeling and Simulation


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