Ongoing Positive Selection Drives the Evolution of SARS-CoV-2 Genomes
- Author:
Hou YALI
1
,
2
;
Zhao SHILEI
;
Liu QI
;
Zhang XIAOLONG
;
Sha TONG
;
Su YANKAI
;
Zhao WENMING
;
Bao YIMING
;
Xue YONGBIAO
;
Chen HUA
Author Information
1. Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China
2. University of Chinese Academy of Sciences,Beijing 100049,China
- Keywords:
COVID-19;
SARS-CoV-2;
Viral evolution;
Natural selection;
Darwinian selection
- From:
Genomics, Proteomics & Bioinformatics
2022;(6):1214-1223
- CountryChina
- Language:Chinese
-
Abstract:
SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December,2019.Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving,and driven by adaptation to the new host and environments is still under debate.Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend,and providing guidance for disease control and treatments.Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30,2021,we demonstrate with popula-tion genetic evidence that during the course of SARS-CoV-2 pandemic in humans,1)SARS-CoV-2 genomes are overall conserved under purifying selection,especially for the 14 genes related to viral RNA replication,transcription,and assembly;2)ongoing positive selection is actively driving the evolution of 6 genes(e.g.,S,ORF3a,and N)that play critical roles in molecular processes involving pathogen-host interactions,including viral invasion into and egress from host cells,and viral inhi-bition and evasion of host immune response,possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution.According to an established haplotype phylogenetic relation-ship of 138 viral clusters,a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters,of which multiple mutations potentially conferring alterations in viral transmis-sibility,pathogenicity,and virulence of SARS-CoV-2 are highlighted,warranting attention.