PDF(Pubmed)
Abstract：
SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus\'s macro- and microevolution. Understanding the molecular mechanisms of mutations in the mutational hotspots (positions, loci with recurrent mutations, and nucleotide context) is important for disentangling roles of mutagenesis and selection. In the SARS-CoV-2 genome, deletions and insertions are frequently associated with repetitive sequences, whereas C>U substitutions are often surrounded by nucleotides resembling the APOBEC mutable motifs. We describe various approaches to mutation spectra analyses, including the context features of RNAs that are likely to be involved in the generation of recurrent mutations. We also discuss the interplay between mutations and natural selection as a complex evolutionary trend. The substantial variability and complexity of pipelines for the reconstruction of mutations and the huge number of genomic sequences are major problems for the analyses of mutations in the SARS-CoV-2 genome. As a solution, we advocate for the development of a centralized database of predicted mutations, which needs to be updated on a regular basis.
摘要：
SARS-CoV-2自2019年底出现以来已经积累了许多突变。导致氨基酸置换的核苷酸置换构成了自然选择的主要材料。插入,删除,替代似乎对冠状病毒的宏观和微观进化至关重要。了解突变热点中突变的分子机制(位置，具有反复突变的基因座，和核苷酸上下文）对于解开诱变和选择的作用很重要。在SARS-CoV-2基因组中,缺失和插入经常与重复序列相关，而C>U取代通常被类似于APOBEC可突变基序的核苷酸包围。我们描述了突变光谱分析的各种方法，包括可能参与复发突变产生的RNA的背景特征。我们还讨论了突变与自然选择之间的相互作用，这是一种复杂的进化趋势。用于重建突变的管道的大量可变性和复杂性以及大量的基因组序列是SARS-CoV-2基因组中突变分析的主要问题。作为解决方案,我们主张开发一个预测突变的集中数据库，需要定期更新。
