Yanqun Wang1, Daxi Wang2,3, Lu Zhang4, Wanying Sun2,3,5, Zhaoyong Zhang1, Weijun Chen5,6, Airu Zhu1, Yongbo Huang1, Fei Xiao7, Jinxiu Yao8, Mian Gan1, Fang Li1, Ling Luo1, Xiaofang Huang1, Yanjun Zhang1, Sook-San Wong1, Xinyi Cheng2,9, Jingkai Ji2,3,10, Zhihua Ou2,3, Minfeng Xiao2,3, Min Li2,3,5, Jiandong Li2,3,5, Peidi Ren2,3, Ziqing Deng2,3, Huanzi Zhong2,3, Xun Xu2,11, Tie Song12, Chris Ka Pun Mok1,13, Malik Peiris1,13, Nanshan Zhong1, Jingxian Zhao14, Yimin Li15, Junhua Li16,17,18, Jincun Zhao19,20. 1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. 2. BGI-Shenzhen, Shenzhen, 518083, China. 3. Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China. 4. Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, 510060, Guangdong, China. 5. BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China. 6. BGI PathoGenesis Pharmaceutical Technology Co., Ltd, BGI-Shenzhen, Shenzhen, 518083, China. 7. Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, Guangdong, China. 8. Yangjiang People's Hospital, Yangjiang, Guangdong, China. 9. School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China. 10. School of Future Technology, University of Chinese Academy of Sciences, Beijing, 101408, China. 11. Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, 518120, China. 12. Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China. 13. The HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, 19406, China. 14. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. zhaojingxian@gird.cn. 15. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. dryiminli@vip.163.com. 16. BGI-Shenzhen, Shenzhen, 518083, China. lijunhua@genomics.cn. 17. Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China. lijunhua@genomics.cn. 18. School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China. lijunhua@genomics.cn. 19. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. zhaojincun@gird.cn. 20. Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, 510060, Guangdong, China. zhaojincun@gird.cn.
Abstract
BACKGROUND: Since early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. METHODS: Using high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19 patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT). RESULTS: The 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks. CONCLUSIONS: Our findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.
BACKGROUND: Since early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. METHODS: Using high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT). RESULTS: The 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks. CONCLUSIONS: Our findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.
Authors: Anton Bankevich; Sergey Nurk; Dmitry Antipov; Alexey A Gurevich; Mikhail Dvorkin; Alexander S Kulikov; Valery M Lesin; Sergey I Nikolenko; Son Pham; Andrey D Prjibelski; Alexey V Pyshkin; Alexander V Sirotkin; Nikolay Vyahhi; Glenn Tesler; Max A Alekseyev; Pavel A Pevzner Journal: J Comput Biol Date: 2012-04-16 Impact factor: 1.479
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Authors: Francisco Barona-Gómez; Luis Delaye; Erik Díaz-Valenzuela; Fabien Plisson; Arely Cruz-Pérez; Mauricio Díaz-Sánchez; Christian A García-Sepúlveda; Alejandro Sanchez-Flores; Rafael Pérez-Abreu; Francisco J Valencia-Valdespino; Natali Vega-Magaña; José Francisco Muñoz-Valle; Octavio Patricio García-González; Sofía Bernal-Silva; Andreu Comas-García; Angélica Cibrián-Jaramillo Journal: Microb Genom Date: 2021-11