Global SNP analysis of 11,183 SARS-CoV-2 strains reveals high genetic diversity
Global SNP analysis of 11,183 SARS-CoV-2 strains reveals high genetic diversity
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DOI：
10.1111/tbed.13931
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发表时间：
2020-12-08
影响因子：
4.3
通讯作者：
Wang, Leyi
中科院分区：
文献类型：
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作者：
Yuan, Fangfeng;Wang, Liping;Wang, Leyi
自二零一九年十二月首次发现以来，COVID-19已于数月内迅速蔓延至全球，而COVID-19病例仍在全球大多数国家迅速激增。病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在自然界中迅速适应和进化。截至5月13日，GISAID中有16，092个SARS-CoV-2全基因组可用，我们删除了质量较差的基因组，并对剩余的11，183个病毒基因组进行了突变分析。所有序列的全球分析确定了整个基因组的所有单核苷酸多态性（SNP）和具有高突变频率的关键SNP，这些SNP有助于全球菌株的五进化枝分类。共发现119个SNP位点，其中74个非同义突变，43个同义突变和2个基因间区突变。对全基因组突变谱的地理模式的分析揭示了每个大陆之间的差异。从C到T的过渡突变代表了基因组中最多的突变类型，表明病毒在宿主中的快速进化和适应。在整个基因组中发现的氨基酸（AA）缺失和插入导致病毒蛋白长度的变化和潜在的功能改变。对每个基因的突变谱进行了分析，结果表明，核衣壳基因表现出最高的突变频率，其次是Nsp 2，Nsp 3和刺突基因。我们进一步关注四种关键病毒蛋白的非同义突变分布，具有75个突变的刺突，具有41个突变的RNA依赖性RNA聚合酶，具有22个突变的3C样蛋白酶和具有10个突变的木瓜蛋白酶样蛋白酶。结果表明，这四种蛋白关键位点的非同义突变对开发抗病毒药物和其他对抗措施构成了巨大挑战。总体而言，这项研究提供了更多的了解SARS-CoV-2的遗传多样性/变异性和抗病毒治疗药物的发展的见解。
Since first identified in December of 2019, COVID-19 has been quickly spreading to the world in few months and COVID-19 cases are still undergoing rapid surge in most countries worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adapts and evolves rapidly in nature. With the availability of 16,092 SARS-CoV-2 full genomes in GISAID as of 13 May, we removed the poor-quality genomes and performed mutational profiling analysis for the remaining 11,183 viral genomes. Global analysis of all sequences identified all single nucleotide polymorphisms (SNPs) across the whole genome and critical SNPs with high mutation frequency that contributes to five-clade classification of global strains. A total of 119 SNPs were found with 74 non-synonymous mutations, 43 synonymous mutations and two mutations in intergenic regions. Analysis of geographic pattern of mutational profiling for the whole genome reveals differences between each continent. A transition mutation from C to T represents the most mutation types across the genome, suggesting rapid evolution and adaptation of the virus in host. Amino acid (AA) deletions and insertions found across the genome results in changes in viral protein length and potential function alteration. Mutational profiling for each gene was analysed, and results show that nucleocapsid gene demonstrates the highest mutational frequency, followed by Nsp2, Nsp3 and Spike gene. We further focused on non-synonymous mutational distributions on four key viral proteins, spike with 75 mutations, RNA-dependent-RNA-polymerase with 41 mutations, 3C-like protease with 22 mutations and Papain-like protease with 10 mutations. Results show that non-synonymous mutations on critical sites of these four proteins pose great challenge for development of anti-viral drugs and other countering measures. Overall, this study provides more understanding of genetic diversity/variability of SARS-CoV-2 and insights for development of anti-viral therapeutics.