Mutations, Recombination and Insertion in the Evolution of 2019-nCoV

Wu, Aiping; Niu, Peihua; Wang, Lulan; Zhou, Hangyu; Zhao, Xiang; Wang, Wenling; Wang, Jingfeng; Ji, Chengyang; Ding, Xiao; Wang, Xianyue; Lu, Roujian; Gold, Sarah; Aliyari, Saba; Zhang, Shilei; Vikram, Ellee; Zou, Angela; Lenh, Emily; Chen, Janet; Ye, Fei; Han, Na; Peng, Yousong; Guo, Haitao; Wu, Guizhen; Jiang, Taijiao; Tan, Wenjie; Cheng, Genhong

Background The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. Methods We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Results Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Conclusions Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. One Sentence Summary Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.