Two-step fitness selection for intra-host variations in SARS-CoV-2

Jiarui Li; Pengcheng Du; Lijiang Yang; Ju Zhang; Chuan Song; Danying Chen; Yangzi Song; Nan Ding; Mingxi Hua; Kai Han; Rui Song; Wen Xie; Zhihai Chen; Xianbo Wang; Jingyuan Liu; Yanli Xu; Guiju Gao; Qi Wang; Lin Pu; Lin Di; Jie Li; Jinglin Yue; Junyan Han; Xuesen Zhao; Yonghong Yan; Fengting Yu; Angela R Wu; Fujie Zhang; Yi Qin Gao; Yanyi Huang; Jianbin Wang; Hui Zeng; Chen Chen

doi:10.1016/j.celrep.2021.110205

Two-step fitness selection for intra-host variations in SARS-CoV-2

Cell Rep. 2022 Jan 11;38(2):110205. doi: 10.1016/j.celrep.2021.110205. Epub 2021 Dec 16.

Authors

Jiarui Li¹, Pengcheng Du¹, Lijiang Yang², Ju Zhang¹, Chuan Song¹, Danying Chen¹, Yangzi Song¹, Nan Ding¹, Mingxi Hua¹, Kai Han¹, Rui Song³, Wen Xie³, Zhihai Chen³, Xianbo Wang³, Jingyuan Liu³, Yanli Xu³, Guiju Gao³, Qi Wang³, Lin Pu³, Lin Di⁴, Jie Li⁵, Jinglin Yue⁶, Junyan Han¹, Xuesen Zhao¹, Yonghong Yan¹, Fengting Yu³, Angela R Wu⁷, Fujie Zhang⁸, Yi Qin Gao⁹, Yanyi Huang¹⁰, Jianbin Wang¹¹, Hui Zeng¹², Chen Chen¹³

Affiliations

¹ Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P. R. China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, P. R. China.
² Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.
³ Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P. R. China.
⁴ Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China; School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen 518055, China.
⁵ School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
⁶ Peking University Ditan Teaching Hospital, Beijing 100015, China.
⁷ Division of Life Science, Hong Kong University of Science and Technology, Hong Kong SAR, P.R. China; Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong SAR, P.R. China.
⁸ Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P. R. China. Electronic address: treatment@chinaaids.cn.
⁹ Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China; Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen 518055, China. Electronic address: gaoyq@pku.edu.cn.
¹⁰ Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China; School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen 518055, China; Chinese Institute for Brain Research, Beijing 102206, China. Electronic address: yanyi@pku.edu.cn.
¹¹ School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China; Chinese Institute for Brain Research, Beijing 102206, China. Electronic address: jianbinwang@tsinghua.edu.cn.
¹² Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. Electronic address: zenghui@ccmu.edu.cn.
¹³ Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. Electronic address: chenchen1@ccmu.edu.cn.

Abstract

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.

Keywords: SARS-CoV-2; dynamic genetic divergence; intra-host variation; positive selection.

Publication types

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

MeSH terms

Adolescent
Adult
Aged
COVID-19 / virology*
Child
Child, Preschool
Female
Genome, Viral / genetics
Host-Pathogen Interactions / genetics*
Humans
Infant
Infant, Newborn
Male
Middle Aged
Mutation / genetics
Phylogeny
Polymorphism, Single Nucleotide / genetics
SARS-CoV-2 / genetics*
Spike Glycoprotein, Coronavirus / genetics
Vaccine Development / methods
Young Adult

Substances

Spike Glycoprotein, Coronavirus