tetano
Editor, Senior Moderator
Cell Rep
. 2021 Dec 16;110205.
doi: 10.1016/j.celrep.2021.110205. Online ahead of print.
Two-step fitness selection for intra-host variations in SARS-CoV-2
Jiarui Li[SUP] 1 [/SUP], Pengcheng Du[SUP] 1 [/SUP], Lijiang Yang[SUP] 2 [/SUP], Ju Zhang[SUP] 1 [/SUP], Chuan Song[SUP] 1 [/SUP], Danying Chen[SUP] 1 [/SUP], Yangzi Song[SUP] 1 [/SUP], Nan Ding[SUP] 1 [/SUP], Mingxi Hua[SUP] 1 [/SUP], Kai Han[SUP] 1 [/SUP], Rui Song[SUP] 3 [/SUP], Wen Xie[SUP] 3 [/SUP], Zhihai Chen[SUP] 3 [/SUP], Xianbo Wang[SUP] 3 [/SUP], Jingyuan Liu[SUP] 3 [/SUP], Yanli Xu[SUP] 3 [/SUP], Guiju Gao[SUP] 3 [/SUP], Qi Wang[SUP] 3 [/SUP], Lin Pu[SUP] 3 [/SUP], Lin Di[SUP] 4 [/SUP], Jie Li[SUP] 5 [/SUP], Jinglin Yue[SUP] 6 [/SUP], Junyan Han[SUP] 1 [/SUP], Xuesen Zhao[SUP] 1 [/SUP], Yonghong Yan[SUP] 1 [/SUP], Fengting Yu[SUP] 3 [/SUP], Angela R Wu[SUP] 7 [/SUP], Fujie Zhang[SUP] 8 [/SUP], Yi Qin Gao[SUP] 9 [/SUP], Yanyi Huang[SUP] 10 [/SUP], Jianbin Wang[SUP] 11 [/SUP], Hui Zeng[SUP] 12 [/SUP], Chen Chen[SUP] 13 [/SUP]
Affiliations
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.
. 2021 Dec 16;110205.
doi: 10.1016/j.celrep.2021.110205. Online ahead of print.
Two-step fitness selection for intra-host variations in SARS-CoV-2
Jiarui Li[SUP] 1 [/SUP], Pengcheng Du[SUP] 1 [/SUP], Lijiang Yang[SUP] 2 [/SUP], Ju Zhang[SUP] 1 [/SUP], Chuan Song[SUP] 1 [/SUP], Danying Chen[SUP] 1 [/SUP], Yangzi Song[SUP] 1 [/SUP], Nan Ding[SUP] 1 [/SUP], Mingxi Hua[SUP] 1 [/SUP], Kai Han[SUP] 1 [/SUP], Rui Song[SUP] 3 [/SUP], Wen Xie[SUP] 3 [/SUP], Zhihai Chen[SUP] 3 [/SUP], Xianbo Wang[SUP] 3 [/SUP], Jingyuan Liu[SUP] 3 [/SUP], Yanli Xu[SUP] 3 [/SUP], Guiju Gao[SUP] 3 [/SUP], Qi Wang[SUP] 3 [/SUP], Lin Pu[SUP] 3 [/SUP], Lin Di[SUP] 4 [/SUP], Jie Li[SUP] 5 [/SUP], Jinglin Yue[SUP] 6 [/SUP], Junyan Han[SUP] 1 [/SUP], Xuesen Zhao[SUP] 1 [/SUP], Yonghong Yan[SUP] 1 [/SUP], Fengting Yu[SUP] 3 [/SUP], Angela R Wu[SUP] 7 [/SUP], Fujie Zhang[SUP] 8 [/SUP], Yi Qin Gao[SUP] 9 [/SUP], Yanyi Huang[SUP] 10 [/SUP], Jianbin Wang[SUP] 11 [/SUP], Hui Zeng[SUP] 12 [/SUP], Chen Chen[SUP] 13 [/SUP]
Affiliations
- PMID: 34982968
- DOI: 10.1016/j.celrep.2021.110205
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.