Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis

Rongsui Gao; Wenhong Zu; Yang Liu; Junhua Li; Zeyao Li; Yanling Wen; Haiyan Wang; Jing Yuan; Lin Cheng; Shengyuan Zhang; Yu Zhang; Shuye Zhang; Weilong Liu; Xun Lan; Lei Liu; Feng Li; Zheng Zhang

doi:10.1080/21505594.2021.1911477

Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis

Virulence. 2021 Dec;12(1):1209-1226. doi: 10.1080/21505594.2021.1911477.

Authors

Rongsui Gao¹, Wenhong Zu¹, Yang Liu¹, Junhua Li², Zeyao Li³, Yanling Wen¹, Haiyan Wang¹, Jing Yuan⁴, Lin Cheng¹, Shengyuan Zhang¹, Yu Zhang⁵, Shuye Zhang⁶, Weilong Liu¹, Xun Lan⁷, Lei Liu¹, Feng Li⁸, Zheng Zhang^{1

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Affiliations

¹ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
² Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, China.
³ School of Life Sciences, Tsinghua University, Beijing, China.
⁴ Department of Infectious Diseases, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease, Shenzhen, Guangdong Province, China.
⁵ National Supercomputing Center in Shenzhen (Shenzhen Cloud Computing Center), Shenzhen, China.
⁶ Shanghai Public Health Clinical Center, Institute of Biomedical Sciences, Fudan University, Shanghai, China.
⁷ Department of Basic Medical Sciences at School of Medicine, Tsinghua University, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
⁸ Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
⁹ Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science, Shenzhen, Guangdong Province, China.
¹⁰ Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province, China.

Abstract

New SARS-CoV-2 mutants have been continuously indentified with enhanced transmission ever since its outbreak in early 2020. As an RNA virus, SARS-CoV-2 has a high mutation rate due to the low fidelity of RNA polymerase. To study the single nucleotide polymorphisms (SNPs) dynamics of SARS-CoV-2, 158 SNPs with high confidence were identified by deep meta-transcriptomic sequencing, and the most common SNP type was C > T. Analyses of intra-host population diversity revealed that intra-host quasispecies' composition varies with time during the early onset of symptoms, which implicates viral evolution during infection. Network analysis of co-occurring SNPs revealed the most abundant non-synonymous SNP 22,638 in the S glycoprotein RBD region and 28,144 in the ORF8 region. Furthermore, SARS-CoV-2 variations differ in an individual's respiratory tissue (nose, throat, BALF, or sputum), suggesting independent compartmentalization of SARS-CoV-2 populations in patients. The positive selection analysis of the SARS-CoV-2 genome uncovered the positive selected amino acid G251V on ORF3a. Alternative allele frequency spectrum (AAFS) of all variants revealed that ORF8 could bear alternate alleles with high frequency. Overall, the results show the quasispecies' profile of SARS-CoV-2 in the respiratory tract in the first two months after the outbreak.

Keywords: SARS-CoV-2; Single nucleotide polymorphism (SNP); epitopes; host adaptation; intra-host single nucleotide variation (iSNV); quasispecies; selective pressure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Alleles
COVID-19 / virology
Computational Biology
Coronavirus Envelope Proteins / chemistry
Coronavirus Envelope Proteins / genetics
Female
Gene Frequency
Genome, Viral
HEK293 Cells
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Phylogeny*
Polymorphism, Single Nucleotide*
Quasispecies*
SARS-CoV-2 / classification*
SARS-CoV-2 / genetics*
Severity of Illness Index
Young Adult

Substances

Coronavirus Envelope Proteins

Grants and funding

This work was supported by the Central Charity Fund of Chinese Academy of Medical Science [2020-PT310-009];Guangdong Basic and Applied Basic Research Foundation [2019A1515110643]; National Science Fund for Distinguished Young Scholars [82025022]; Shenzhen Science and Technology Innovation Committee [2020A1111350032, JCYJ20190809112205541]; the emergency grants for prevention and control of SARS-CoV-2 of Guangdong province [2020B111108001, 2020B1111340036, 2020B1111340029]; the China Postdoctoral Science Foundation [2019M660837].