Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
J Med Virol. 2021 Mar;93(3):1722-1731. doi: 10.1002/jmv.26545. Epub 2020 Oct 8.
During the first few months of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution in a new host, contrasting hypotheses have been proposed about the way the virus has evolved and diversified worldwide. The aim of this study was to perform a comprehensive evolutionary analysis to describe the human outbreak and the evolutionary rate of different genomic regions of SARS-CoV-2. The molecular evolution in nine genomic regions of SARS-CoV-2 was analyzed using three different approaches: phylogenetic signal assessment, emergence of amino acid substitutions, and Bayesian evolutionary rate estimation in eight successive fortnights since the virus emergence. All observed phylogenetic signals were very low and tree topologies were in agreement with those signals. However, after 4 months of evolution, it was possible to identify regions revealing an incipient viral lineage formation, despite the low phylogenetic signal since fortnight 3. Finally, the SARS-CoV-2 evolutionary rate for regions nsp3 and S, the ones presenting greater variability, was estimated as 1.37 × 10 and 2.19 × 10 substitution/site/year, respectively. In conclusion, results from this study about the variable diversity of crucial viral regions and determination of the evolutionary rate are consequently decisive to understand essential features of viral emergence. In turn, findings may allow the first-time characterization of the evolutionary rate of S protein, crucial for vaccine development.
在严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)在新宿主中进化的最初几个月中,关于病毒在全球范围内进化和多样化的方式提出了相互矛盾的假设。本研究的目的是进行全面的进化分析,以描述 SARS-CoV-2 的人类爆发和不同基因组区域的进化率。使用三种不同方法分析了 SARS-CoV-2 的九个基因组区域的分子进化:系统发育信号评估、氨基酸取代的出现以及自病毒出现以来连续八个双周的贝叶斯进化率估计。所有观察到的系统发育信号都非常低,并且树拓扑结构与这些信号一致。然而,在进化 4 个月后,尽管自第 3 个双周以来系统发育信号很低,但仍有可能识别出显示病毒谱系形成初期的区域。最后,对 nsp3 和 S 区域的 SARS-CoV-2 进化率进行了估计,这两个区域的变异性较大,分别为 1.37×10 和 2.19×10 个替换/位点/年。总之,本研究关于关键病毒区域的可变多样性和进化率的确定的结果对于理解病毒出现的基本特征是至关重要的。反过来,这些发现可能首次对 S 蛋白的进化率进行了特征描述,这对疫苗开发至关重要。