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Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2

Jingsong Zhang, Yang Zhang, Junyan Kang, Shuiye Chen, View ORCID ProfileYongqun He, Benhao Han, Mofang Liu, Lina Lu, Li Li, Zhigang Yi, Luonan Chen
doi: https://doi.org/10.1101/2021.04.16.440141
Jingsong Zhang
1Key Laboratory of Systems Biology, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
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Yang Zhang
2Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
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Junyan Kang
3State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
4University of Chinese Academy of Sciences, Shanghai 200031, China
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Shuiye Chen
2Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
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Yongqun He
5Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
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  • ORCID record for Yongqun He
Benhao Han
1Key Laboratory of Systems Biology, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
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Mofang Liu
3State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
4University of Chinese Academy of Sciences, Shanghai 200031, China
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Lina Lu
1Key Laboratory of Systems Biology, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
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Li Li
6Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
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Zhigang Yi
2Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
7Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
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  • For correspondence: lnchen@sibs.ac.cn zgyi@fudan.edu.cn
Luonan Chen
1Key Laboratory of Systems Biology, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
8School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
9Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China
10Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
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  • For correspondence: lnchen@sibs.ac.cn zgyi@fudan.edu.cn
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Abstract

The presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole genome represents a large number of potential co-mutations with very strong statistical significances (p value<E–44). In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5’UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly enhanced the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.

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-NC-ND 4.0 International license.
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Posted April 16, 2021.
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Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2
Jingsong Zhang, Yang Zhang, Junyan Kang, Shuiye Chen, Yongqun He, Benhao Han, Mofang Liu, Lina Lu, Li Li, Zhigang Yi, Luonan Chen
bioRxiv 2021.04.16.440141; doi: https://doi.org/10.1101/2021.04.16.440141
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Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2
Jingsong Zhang, Yang Zhang, Junyan Kang, Shuiye Chen, Yongqun He, Benhao Han, Mofang Liu, Lina Lu, Li Li, Zhigang Yi, Luonan Chen
bioRxiv 2021.04.16.440141; doi: https://doi.org/10.1101/2021.04.16.440141

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