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Published on: January 9, 2019
Adaptive Evolution of the Spike Protein in Coronaviruses
Xiaolu Tang1, Zhaohui Qian2, Xuemei Lu3,4
1State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences, Peking University, Beijing, China.
Abstract:
Coronaviruses are single-stranded, positive-sense RNA viruses that can infect many mammal and avian species. The Spike (S) protein of coronaviruses 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 being able to recognize the same receptor and coronaviruses from the same genus able to bind distinct receptors. As the coronavirus disease 2019 pandemic has developed, many changes in the S protein have been under positive selection by altering the receptor-binding affinity, reducing antibody neutralization activities, or affecting T-cell responses. It is intriguing to determine whether the selection pressure on the S gene differs between severe acute respiratory syndrome coronavirus 2 (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 both SARS-CoV-2 and other coronaviruses. Although the S1 N-terminal domain exhibits signals of positive selection in the pairwise comparisons in all four coronavirus genera, positive selection is primarily detected in the S1 C-terminal domain (the receptor-binding domain) 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.
Insights
The Spike (S) gene in coronaviruses, including SARS-CoV-2, shows positive selection. This evolution, especially in the S1 receptor-binding domain, is driven by host shifts and human interventions like vaccination.
Area of Science:
- Virology
- Molecular Evolution
- Genomics
Background:
- Coronaviruses are RNA viruses infecting mammals and birds.
- The Spike (S) protein mediates host cell entry via receptor binding.
- S protein evolution is complex, with varying receptor interactions across genera.
Purpose of the Study:
- To investigate selection pressures on the coronavirus Spike (S) gene.
- To compare evolutionary patterns between SARS-CoV-2 and other coronaviruses.
- To understand the impact of host shifts on S gene evolution.
Main Methods:
- Phylogenetic analysis of coronavirus S genes.
- Identification of positively selected sites within the S gene.
- Comparative analysis across different coronavirus genera.
Main Results:
- The S gene, particularly the S1 region, is under positive selection in both SARS-CoV-2 and other coronaviruses.
- Positive selection signals are observed in the S1 N-terminal domain across all four genera.
- Ongoing SARS-CoV-2 evolution shows primary positive selection in the S1 C-terminal (receptor-binding) domain.
Conclusions:
- The S gene experiences significant positive selection, crucial for viral adaptation.
- SARS-CoV-2's evolution highlights selection pressure on the receptor-binding domain, influenced by human adaptation and interventions.
- Understanding these evolutionary dynamics is key to managing coronavirus outbreaks.
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