Intra-host variation and evolutionary dynamics of SARS-CoV-2 populations in COVID-19 patients
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..
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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Enthalten in: |
Genome medicine - 13(2021), 1 vom: 22. Feb. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Wang, Yanqun [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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Anmerkungen: |
© The Author(s) 2021 |
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doi: |
10.1186/s13073-021-00847-5 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
OLC212389205X |
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520 | |a 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. | ||
650 | 4 | |a SARS-CoV-2 | |
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650 | 4 | |a Intra-host | |
650 | 4 | |a Variation | |
650 | 4 | |a Dynamics | |
700 | 1 | |a Wang, Daxi |4 aut | |
700 | 1 | |a Zhang, Lu |4 aut | |
700 | 1 | |a Sun, Wanying |4 aut | |
700 | 1 | |a Zhang, Zhaoyong |4 aut | |
700 | 1 | |a Chen, Weijun |4 aut | |
700 | 1 | |a Zhu, Airu |4 aut | |
700 | 1 | |a Huang, Yongbo |4 aut | |
700 | 1 | |a Xiao, Fei |4 aut | |
700 | 1 | |a Yao, Jinxiu |4 aut | |
700 | 1 | |a Gan, Mian |4 aut | |
700 | 1 | |a Li, Fang |4 aut | |
700 | 1 | |a Luo, Ling |4 aut | |
700 | 1 | |a Huang, Xiaofang |4 aut | |
700 | 1 | |a Zhang, Yanjun |4 aut | |
700 | 1 | |a Wong, Sook-san |4 aut | |
700 | 1 | |a Cheng, Xinyi |4 aut | |
700 | 1 | |a Ji, Jingkai |4 aut | |
700 | 1 | |a Ou, Zhihua |4 aut | |
700 | 1 | |a Xiao, Minfeng |4 aut | |
700 | 1 | |a Li, Min |4 aut | |
700 | 1 | |a Li, Jiandong |4 aut | |
700 | 1 | |a Ren, Peidi |4 aut | |
700 | 1 | |a Deng, Ziqing |4 aut | |
700 | 1 | |a Zhong, Huanzi |4 aut | |
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700 | 1 | |a Song, Tie |4 aut | |
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700 | 1 | |a Li, Yimin |4 aut | |
700 | 1 | |a Li, Junhua |4 aut | |
700 | 1 | |a Zhao, Jincun |4 aut | |
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