Adaptive Evolution of the Spike Protein in Coronaviruses

Coronaviruses are single-stranded, positive-sense RNA viruses infecting many mammal and avian species. The Spike (S) protein binds host-cell receptors to promote viral entry. Receptor interactions are complex: different coronavirus genera can recognize the same receptor, while viruses within a genus can bind distinct receptors. During the COVID-19 pandemic, many changes in the S protein have been under positive selection by altering receptor-binding affinity, reducing antibody neutralization, or affecting T-cell responses. We asked whether selection pressure on S differs between SARS-CoV-2 and other coronaviruses due to the host shift to humans. We show that the S gene, particularly S1, has experienced positive selection in both SARS-CoV-2 and other coronaviruses. While pairwise comparisons across all four coronavirus genera reveal positive selection signals in the S1 N-terminal domain (NTD), ongoing SARS-CoV-2 evolution shows selection primarily in the S1 C-terminal domain (CTD; receptor-binding domain, RBD), likely owing to human host settings with widespread natural infection and vaccination.

Xiaolu Tang, Zhaohui Qian, Xuemei Lu, Jian Lu