Adaptive evolution of the Spike protein in coronaviruses

Coronaviruses are single-stranded, positive-sense RNA viruses that can infect many mammal and avian species. The Spike (S) protein of coronavirus binds to a receptor on the host cell surface to promote viral entry. The interactions between the S proteins of coronaviruses and receptors of host cells are extraordinarily complex, with coronaviruses from different genera could recognize the same receptor and coronaviruses from the same genus could bind distinct receptors. As the COVID-19 pandemic has developed, many changes in the S protein were under positive selection by altering the receptor binding affinity, reducing antibody neutralization activities, or affecting T-cell responses. It will be intriguing to determine whether the selection pressure on the S gene differs between SARS-CoV-2 and other coronaviruses due to the host shift from nonhuman animals to humans. Here, we show that the S gene, particularly the S1 region, has experienced positive selection in SARS-CoV-2 and other coronaviruses. Although the S1-NTD domain exhibits signals of positive selection in the pairwise comparisons in all four coronavirus genera, positive selection was primarily detected in the S1-CTD domain (the receptor-binding domain, RBD) in the ongoing evolution of SARS-CoV-2, possibly owing to the change in host settings and the widespread natural infection and SARS-CoV-2 vaccination in humans.

Here, we provided the sequence ID used in our manuscript, for reproducibility purpose.