Department of Pediatrics, Johns Hopkins University School of Medicine, MD, USA.
Network Reconstruction & Analysis (NetRA) Lab, Department of Computer Applications, Sikkim University, Gangtok, India.
Genomics. 2021 Jul;113(4):2177-2188. doi: 10.1016/j.ygeno.2021.05.008. Epub 2021 May 19.
The prevailing COVID-19 pandemic has drawn the attention of the scientific community to study the evolutionary origin of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). This study is a comprehensive quantitative analysis of the protein-coding sequences of seven human coronaviruses (HCoVs) to decipher the nucleotide sequence variability and codon usage patterns. It is essential to understand the survival ability of the viruses, their adaptation to hosts, and their evolution. The current analysis revealed a high abundance of the relative dinucleotide (odds ratio), GC and CT pairs in the first and last two codon positions, respectively, as well as a low abundance of the CG pair in the last two positions of the codon, which might be related to the evolution of the viruses. A remarkable level of variability of GC content in the third position of the codon among the seven coronaviruses was observed. Codons with high RSCU values are primarily from the aliphatic and hydroxyl amino acid groups, and codons with low RSCU values belong to the aliphatic, cyclic, positively charged, and sulfur-containing amino acid groups. In order to elucidate the evolutionary processes of the seven coronaviruses, a phylogenetic tree (dendrogram) was constructed based on the RSCU scores of the codons. The severe and mild categories CoVs were positioned in different clades. A comparative phylogenetic study with other coronaviruses depicted that SARS-CoV-2 is close to the CoV isolated from pangolins (Manis javanica, Pangolin-CoV) and cats (Felis catus, SARS(r)-CoV). Further analysis of the effective number of codon (ENC) usage bias showed a relatively higher bias for SARS-CoV and MERS-CoV compared to SARS-CoV-2. The ENC plot against GC3 suggested that the mutational bias might have a role in determining the codon usage variation among candidate viruses. A codon adaptability study on a few human host parasites (from different kingdoms), including CoVs, showed a diverse adaptability pattern. SARS-CoV-2 and SARS-CoV exhibit relatively lower but similar codon adaptability compared to MERS-CoV.
当前的 COVID-19 大流行引起了科学界的关注，促使他们研究严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）的进化起源。本研究对七种人类冠状病毒（HCoV）的蛋白质编码序列进行了全面的定量分析，旨在破译核苷酸序列变异性和密码子使用模式。了解病毒的生存能力、宿主适应性和进化至关重要。目前的分析表明，在第一和最后两个密码子位置，相对二核苷酸（优势比）GC 和 CT 对的丰度较高，而在密码子的最后两个位置 CG 对的丰度较低，这可能与病毒的进化有关。在七种冠状病毒中，观察到第三密码子位置的 GC 含量具有显著的可变性。具有高 RSCU 值的密码子主要来自脂肪族和羟基氨基酸组，而具有低 RSCU 值的密码子属于脂肪族、环状、正电荷和含硫氨基酸组。为了阐明七种冠状病毒的进化过程，根据密码子的 RSCU 值构建了系统发育树（树状图）。严重和轻度 CoV 被定位在不同的分支中。与其他冠状病毒的比较系统发育研究表明，SARS-CoV-2 与从穿山甲（Manis javanica，穿山甲 CoV）和猫（Felis catus，SARS(r)-CoV）中分离的 CoV 密切相关。对有效密码子数（ENC）使用偏性的进一步分析表明，与 SARS-CoV-2 相比，SARS-CoV 和 MERS-CoV 具有相对较高的偏性。ENC 图与 GC3 的对比表明，突变偏性可能在确定候选病毒之间的密码子使用变异中起作用。对少数人类宿主寄生虫（来自不同的界）（包括 CoV）的密码子适应性进行了研究，结果显示出多样化的适应性模式。与 MERS-CoV 相比，SARS-CoV-2 和 SARS-CoV 的密码子适应性相对较低但相似。
