Intra-host variation and evolutionary dynamics of SARS-CoV-2 populations in COVID-19 patients
Open Access
- 22 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genome Medicine
- Vol. 13 (1), 1-13
- https://doi.org/10.1186/s13073-021-00847-5
Abstract
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. 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). 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. 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.Keywords
Funding Information
- the national key Research and Development Program of China (2018YFC1200100, 2018ZX10301403, 2018YFC1311900)
- the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology (2020YFC0841400)
- the emergency grants for prevention and control of SARS-CoV-2 of Guangdong province (2020B1111320003, 2020B111108001, 2018B020207013, 2020B111112003)
- the Guangdong Province Basic and Applied Basic Research Fund (2020A1515010911)
- Guangdong Science and Technology Foundation (2019B030316028)
- Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011)
- Guangzhou Medical University High-level University Innovation Team Training Program ([2017] No.159)
- National Natural Science Foundation of China (81702047, 81772191, 91842106 and 8181101118)
- State Key Laboratory of Respiratory Disease (SKLRD-QN-201715, SKLRD-QN-201912 and SKLRD-Z-202007)
This publication has 63 references indexed in Scilit:
- Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic studyThe Lancet, 2013
- Viral Quasispecies EvolutionMicrobiology and Molecular Biology Reviews, 2012
- SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell SequencingJournal of Computational Biology, 2012
- A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEffFly, 2012
- Contribution of Intra- and Interhost Dynamics to Norovirus EvolutionJournal of Virology, 2012
- Dynamic Coinfection with Multiple Viral Subtypes in Acute Hepatitis CThe Journal of Infectious Diseases, 2010
- Fast and accurate long-read alignment with Burrows–Wheeler transformBioinformatics, 2010
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- MAFFT version 5: improvement in accuracy of multiple sequence alignmentNucleic Acids Research, 2005
- RNA VIRUS MUTATIONS AND FITNESS FOR SURVIVALAnnual Review of Microbiology, 1997