Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection

TLDR

COVID‑19 is a global pandemic caused by SARS‑CoV‑2, and widespread purifying selection and recombination among coronaviruses across hosts suggest a common evolutionary mechanism for emerging human coronaviruses. The study aims to elucidate SARS‑CoV‑2’s origins to prevent future zoonoses and guide drug and vaccine development, emphasizing that extensive recombination and strong purifying selection among coronaviruses drive its emergence. Strong purifying selection around the spike protein’s receptor‑binding motif is shared across bat, pangolin, and human coronaviruses, and the entire RBM in SARS‑CoV‑2 was acquired by recombination with pangolin coronaviruses, likely enabling human infection.

Abstract

Abstract COVID-19 has become a global pandemic caused by a novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis and for drug discovery and vaccine development. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pangolin and human coronaviruses, indicating similar strong evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species and frequent recombination among coronaviruses suggest a common evolutionary mechanism that could lead to new emerging human coronaviruses. One Sentence Summary Extensive Recombination and Strong Purifying Selection among coronaviruses from different hosts facilitate the emergence of SARS-CoV-2