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SARS-CoV-2 Quasispecies provides insight into its genetic dynamics during infection

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
doi: https://doi.org/10.1101/2020.08.20.258376
Fengming Sun
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
4Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China
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Xiuhua Wang
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
4Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China
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Shun Tan
2Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing 400036, China
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Yunjie Dan
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
4Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China
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Yanqiu Lu
2Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing 400036, China
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Juan Zhang
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
4Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China
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Junli Xu
3Beijing Novogene Company Limited, Beijing 100015, China
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Zhaoxia Tan
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
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Xiaomei Xiang
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
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Yi Zhou
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
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Weiwei He
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
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Xing Wan
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
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Wei Zhang
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
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Yaokai Chen
2Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing 400036, China
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  • For correspondence: gh_deng@hotmail.com tan_wenting@126.com yaokaichen@hotmail.com
Wenting Tan
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
4Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China
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  • For correspondence: gh_deng@hotmail.com tan_wenting@126.com yaokaichen@hotmail.com
Guohong Deng
1Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing 400038, China
4Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China
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  • For correspondence: gh_deng@hotmail.com tan_wenting@126.com yaokaichen@hotmail.com
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Abstract

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 Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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SARS-CoV-2 Quasispecies provides insight into its genetic dynamics during infection
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
bioRxiv 2020.08.20.258376; doi: https://doi.org/10.1101/2020.08.20.258376
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SARS-CoV-2 Quasispecies provides insight into its genetic dynamics during infection
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
bioRxiv 2020.08.20.258376; doi: https://doi.org/10.1101/2020.08.20.258376

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