SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants
Fengming Sun, Xiuhua Wang, Shun Tan, Yunjie Dan, Yanqiu Lu, Juan Zhang, Junli Xu, Zhaoxia Tan, Xiaomei Xiang, Yi Zhou, Weiwei He, Xing Wan, Wei Zhang, Yaokai Chen, Wenting Tan, Guohong Deng
Abstract
RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution. The process is likely achieved by changing the genetic characteristics of key functional genes, such as the spike glycoprotein. Previous studies have applied the next-generation sequencing (NGS) technology to evaluate the quasispecies of SARS-CoV-2, and results indicated a low genetic diversity of the spike gene. However, the NGS platform cannot directly obtain the full haplotypes without assembling, and it is also difficult to predict the extremely low-frequency variations. Therefore, we introduced a single-molecule real-time technology to directly obtain the haplotypes of the RNA population and further study the quasispecies features and intrahost evolution of the spike gene.