奥密克戎BA.1变异株在全球的流行和刺突蛋白的进化分析

Global Prevalence of the Omicron BA.1 Variant and Evolutionary Analysis of the Spike Protein

新型冠状病毒Omicron变异株出现之后,在全球暴发流行过程中不断进化出传播速度更快、免疫逃逸能力更强的进化分支,为了探究BA.1变异株在全球暴发流行的特征及刺突蛋白(Spike,S)基因的进化特征,本研究对其全基因序列的全球报告情况和S基因的进化特征进行了分析。本文通过全球共享流感数据倡议组织(Global Initiative of Sharing All Influenza Data,GISAID)获取Omicron BA.1系列变异株的全基因序列信息,分析BA.1系列变异株S基因氨基酸突变并构建系统进化树和进行贝叶斯系统进化分析。本研究提示全球约有1.2亿人被BA.1系列变异株感染,全球提交的BA.1系列变异株序列数在其出现2个月后达到高峰,5个月后占新型冠状病毒的比例下降到4.38%,累计提交BA.1全基因序列最多的区域是欧洲、美洲;截止2022年10月,BA.1系列变异株中序列提交数占绝对优势的是BA.1.1(42.07%),其次是BA.1(18.81%)。对S基因的氨基酸变异分析显示BA.1有56个进化分支,其中48个分支稳定遗传了Omicron原始株S蛋白中的18个氨基酸突变位点。对BA.1 S基因的进化分析显示其共同祖先形成时间(TMRCA)可追溯到2020年11月,S基因平均碱基替代速率为9.36×10^(-4)替换/位点/年,2021年3月BA.1流行过程中形成两个独立簇,推测G346K、G446S突变位点可能是提高病毒传播力的主要突变。本研究分析了BA.1系列变异株的流行及进化特征,其在短时间内迅速替代Delta毒株,成为全球绝对优势流行株,并有迅速被BA.2亚型代替的潜力。此外,BA.1在全球3~4个月的流行中,逐渐演变出56个进化分支,在全球流行时间短、出现部分稳定遗传的氨基酸突变、进化速率较快。因此,需密切关注Omicron系列变异株基因序列变异变迁、监测新增突变位点,及时研判新变异株的传播力、免疫逃逸能力和致病力。

SARS-CoV-2 Omicron variants have evolved into evolutionary branches with faster transmission and greater immune escape during global outbreak epidemic.To investigate the characteristics of the global outbreak epidemic of BA.1 variants and the evolutionary features of the spike protein(S)gene,the global report of the whole genome sequences and the evolutionary characteristics of the S gene were analyzed.The whole genome sequences information of BA.1 series variants were obtained from GISAID(Global Initiative of Sharing AIl Influenza Data)to analyze the amino acid mutations in S protein of Omicron BA.1 series variants,construct the Bayesian evolutionary tree and conduct the evolutionary analysis.This study suggests that approximately 120 million people worldwide were infected by the BA.1 series variants.Global submitting of BA.1 series variants sequences peaked 2 months after appearance,and decreased to 4.38%of SARS-CoV-2 after 5 months.Europe and the Americas have submitted the largest number of whole genome sequences of BA.1.As of October 2022,the overwhelmingly dominant BA.1 series variant was BA.1.1(42.07%),followed by BA.1(18.81%).Analysis of the S gene and amino acid variation showed that BA.1 had 56 evolutionary branches,48 of which stably inherited 18 amino acid mutation sites from S protein of the original Omicron strain.The evolutionary analysis of the BA.1 S gene showed that the time to most recent common ancestor(TmRca)dated back to November 2020 and the substitution rate of the S gene is approximately 9.36×10^(-4)substitutions/sites/year.Two independent clusters were formed during the BA.1 epidemic in March 2021,and we speculate that the G346K and G446S mutant sites may enhance virus transmission.This study analyzed the prevalence and evolutionary characteristics of the BA.1 series variants,which rapidly replaced the Delta variant and became the dominant epidemic variant worldwide,and is likely to was rapidly replaced by the BA.2 sublineage.In addition,BA.1 gradually evolved into 56 evolutionary branches during the global epidemic of 3-4 months.Furthermore,BA.1 has a short global epidemic time,some stable genetic amino acid mutations,and a fast evolutionary rate.Therefore,it is necessary to pay close attention to the genome sequence variation of Omicron series variants,monitor new mutation sites,and promptly judge the transmission power,immune escape ability and pathogenicity of the new variants.