Laboratory of Molecular Epigenetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
Genes (Basel). 2021 May 27;12(6):826. doi: 10.3390/genes12060826.
The genomic diversity of SARS-CoV-2 has been a focus during the ongoing COVID-19 pandemic. Here, we analyzed the distribution and character of emerging mutations in a data set comprising more than 95,000 virus genomes covering eight major SARS-CoV-2 lineages in the GISAID database, including genotypes arising during COVID-19 therapy. Globally, the C>U transitions and G>U transversions were the most represented mutations, accounting for the majority of single-nucleotide variations. Mutational spectra were not influenced by the time the virus had been circulating in its host or medical treatment. At the amino acid level, we observed about a 2-fold excess of substitutions in favor of hydrophobic amino acids over the reverse. However, most mutations constituting variants of interests of the S-protein (spike) lead to hydrophilic amino acids, counteracting the global trend. The C>U and G>U substitutions altered codons towards increased amino acid hydrophobicity values in more than 80% of cases. The bias is explained by the existing differences in the codon composition for amino acids bearing contrasting biochemical properties. Mutation asymmetries apparently influence the biochemical features of SARS CoV-2 proteins, which may impact protein-protein interactions, fusion of viral and cellular membranes, and virion assembly.
在持续的 COVID-19 大流行期间，SARS-CoV-2 的基因组多样性一直是关注的焦点。在这里，我们分析了超过 95000 个病毒基因组数据集的分布和新兴突变特征，这些基因组涵盖了 GISAID 数据库中的 8 个主要 SARS-CoV-2 谱系，包括在 COVID-19 治疗期间出现的基因型。在全球范围内，C>U 转换和 G>U 颠换是最常见的突变，占大多数单核苷酸变异。突变谱不受病毒在宿主中传播或治疗时间的影响。在氨基酸水平上，我们观察到有利于疏水性氨基酸的取代大约是相反情况的两倍。然而，构成 S 蛋白（刺突）变异感兴趣的大多数突变导致亲水性氨基酸，与全球趋势相反。C>U 和 G>U 取代导致超过 80%的情况下密码子朝着增加的氨基酸疏水性值变化。这种偏差是由具有相反生化特性的氨基酸的密码子组成差异造成的。突变不对称性显然影响 SARS CoV-2 蛋白的生化特性，这可能影响蛋白-蛋白相互作用、病毒和细胞膜融合以及病毒粒子组装。
