Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Kuwait, Kuwait.
Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait, Kuwait.
PLoS One. 2021 May 25;16(5):e0251368. doi: 10.1371/journal.pone.0251368. eCollection 2021.
COVID-19 is challenging healthcare preparedness, world economies, and livelihoods. The infection and death rates associated with this pandemic are strikingly variable in different countries. To elucidate this discrepancy, we analyzed 2431 early spread SARS-CoV-2 sequences from GISAID. We estimated continental-wise admixture proportions, assessed haplotype block estimation, and tested for the presence or absence of strains' recombination. Herein, we identified 1010 unique missense mutations and seven different SARS-CoV-2 clusters. In samples from Asia, a small haplotype block was identified, whereas samples from Europe and North America harbored large and different haplotype blocks with nonsynonymous variants. Variant frequency and linkage disequilibrium varied among continents, especially in North America. Recombination between different strains was only observed in North American and European sequences. In addition, we structurally modelled the two most common mutations, Spike_D614G and Nsp12_P314L, which suggested that these linked mutations may enhance viral entry and replication, respectively. Overall, we propose that genomic recombination between different strains may contribute to SARS-CoV-2 virulence and COVID-19 severity and may present additional challenges for current treatment regimens and countermeasures. Furthermore, our study provides a possible explanation for the substantial second wave of COVID-19 presented with higher infection and death rates in many countries.
COVID-19 对医疗保健准备、世界经济和生计构成了挑战。这种大流行相关的感染率和死亡率在不同国家差异显著。为了阐明这种差异,我们分析了 GISAID 上的 2431 条早期 SARS-CoV-2 序列。我们估计了各大陆的混合比例,评估了单倍型块估计,并检测了菌株重组的存在或缺失。在此,我们确定了 1010 个独特的错义突变和 7 个不同的 SARS-CoV-2 簇。在亚洲样本中,发现了一个小的单倍型块,而来自欧洲和北美的样本则具有带有非同义变异的大而不同的单倍型块。变异频率和连锁不平衡在各大陆之间存在差异,尤其是在北美。仅在北美和欧洲序列中观察到不同菌株之间的重组。此外,我们对两种最常见的突变 Spike_D614G 和 Nsp12_P314L 进行了结构建模,这表明这些连锁突变可能分别增强病毒进入和复制。总的来说,我们提出不同菌株之间的基因组重组可能导致 SARS-CoV-2 的毒力和 COVID-19 的严重程度,并可能对当前的治疗方案和对策提出额外的挑战。此外,我们的研究为许多国家 COVID-19 感染率和死亡率较高的第二波大流行提供了一个可能的解释。