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- Title
Host heterogeneity and epistasis explain punctuated evolution of SARS-CoV-2.
- Authors
Nielsen, Bjarke Frost; Saad-Roy, Chadi M.; Li, Yimei; Sneppen, Kim; Simonsen, Lone; Viboud, Cécile; Levin, Simon A.; Grenfell, Bryan T.
- Abstract
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. Author summary: The coronavirus responsible for the COVID-19 pandemic, SARS-CoV-2, has shown a remarkable ability to evolve novel, increasingly transmissible variants. Using large amounts of viral sequences sampled during the pandemic, we map the genomic diversity over time. We find that the pathogen has followed a clear pattern of punctuated evolution, where periods of genetic drift are interrupted by sudden large increases in diversity followed by similarly abrupt collapses. This is in contrast to the pattern previously identified for influenza, which does not show similarly sudden increases in diversity. Using a mathematical model, we show that the observed pattern can result from rare evolutionary jumps (saltations) occurring within some hosts, in combination with epistasis. One possible explanation for such jumps is accelerated evolution within immunocompromised hosts, underscoring the importance of equitable vaccine distribution. Furthermore, a simple modification of the model to include incomplete cross immunity offers an explanation for recently observed patterns of variant co-circulation.
- Subjects
COVID-19; ENDEMIC diseases; SARS-CoV-2; CROSS reactions (Immunology); EMERGING infectious diseases; GENETIC drift
- Publication
PLoS Computational Biology, 2023, Vol 19, Issue 2, p1
- ISSN
1553-734X
- Publication type
Article
- DOI
10.1371/journal.pcbi.1010896