Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations.
Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations.
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DOI：
10.1371/journal.pone.0240345
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Ibrahimi A
中科院分区：
文献类型：
--
作者：
Laamarti M;Alouane T;Kartti S;Chemao-Elfihri MW;Hakmi M;Essabbar A;Laamarti M;Hlali H;Bendani H;Boumajdi N;Benhrif O;Allam L;El Hafidi N;El Jaoudi R;Allali I;Marchoudi N;Fekkak J;Benrahma H;Nejjari C;Amzazi S;Belyamani L;Ibrahimi A
于二零一九年十二月下旬，中国武汉发现新型病毒感染COVID-19，并成为全球大流行。SARS-CoV-2基因变异的特征对于跟踪和评估其在各国的传播至关重要。在这项研究中，我们收集并分析了来自55个国家的3，067个SARS-CoV-2基因组，这些基因组是在该病毒发病后的前三个月内分离出来的。使用比较基因组学分析，我们追踪了全基因组突变的概况，并比较了研究人群中每种突变的频率。还监测了流行期间突变的累积及其地理位置。结果显示，782个变异位点，其中512个（65.47%）具有非同义效应。突变等位基因的频率揭示了68个复发突变的存在，包括10个热点非同义突变，其在该人群中的患病率高于0.10，分布在6个SARS-CoV-2基因中。这些重复突变在世界地图上的分布表明，某些基因型是特定于地理位置的。我们还鉴定了导致几种单倍型存在的共同发生的突变。此外，随着时间的推移，进化已经显示出突变共同积累的机制，这可能会影响SARS-CoV-2的严重性和传播。遗传学分析确定了两个主要的分支C1和C2分别携带突变L3606 F和G614 D，这两个突变都是首次在中国出现。另一方面，选择压力的分析揭示了负选择残基的存在，其可以被考虑作为治疗靶点。我们还创建了一个包容性的统一数据库（http：covid-19.medbiotech.ma），列出了本研究中发现的SARS-CoV-2基因组的所有遗传变异，并在世界各地进行了地理分析。
In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variants sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 68 recurrent mutations, including ten hotspot non-synonymous mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed that certain genotypes are specific to geographic locations. We also identified co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. The phylogentic analysis identified two major Clades C1 and C2 harboring mutations L3606F and G614D, respectively and both emerging for the first time in China. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets. We have also created an inclusive unified database (http://covid-19.medbiotech.ma) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.
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