RT Journal Article SR Electronic T1 SARS-CoV-2 Quasispecies provides insight into its genetic dynamics during infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.20.258376 DO 10.1101/2020.08.20.258376 A1 Fengming Sun A1 Xiuhua Wang A1 Shun Tan A1 Yunjie Dan A1 Yanqiu Lu A1 Juan Zhang A1 Junli Xu A1 Zhaoxia Tan A1 Xiaomei Xiang A1 Yi Zhou A1 Weiwei He A1 Xing Wan A1 Wei Zhang A1 Yaokai Chen A1 Wenting Tan A1 Guohong Deng YR 2020 UL http://biorxiv.org/content/early/2020/08/20/2020.08.20.258376.abstract AB A novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has been pandemic worldwide. The genetic dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. However, no quasispecies data of SARS-CoV-2 have been reported yet. To explore quasispecies haplotypes and its transmission characteristics, we carried out single-molecule real-time (SMRT) sequencing of the full-length of SARS-CoV-2 spike gene within 14 RNA samples from 2 infection clusters, covering first-to third-generation infected-patients. We observed a special quasispecies structure of SARS-CoV-2 (modeled as ‘One-King’): one dominant haplotype (mean abundance ~70.15%) followed by numerous minor haplotypes (mean abundance < 0.10%). We not only discovered a novel dominant haplotype of F1040 but also realized that minor quasispecies were also worthy of attention. Notably, some minor haplotypes (like F1040 and currently pandemic one G614) could potentially reveal adaptive and converse into the dominant one. However, minor haplotypes exhibited a high transmission bottleneck (~6% could be stably transmitted), and the new adaptive/dominant haplotypes were likely originated from genetic variations within a host rather than transmission. The evolutionary rate was estimated as 2.68-3.86 × 10−3 per site per year, which was larger than the estimation at consensus genome level. The ‘One-King’ model and conversion event expanded our understanding of the genetic dynamics of SARS-CoV-2, and explained the incomprehensible phenomenon at the consensus genome level, such as limited cumulative mutations and low evolutionary rate. Moreover, our findings suggested the epidemic strains may be multi-host origin and future traceability would face huge difficulties.Competing Interest StatementThe authors have declared no competing interest.