摘　要：微卫星（microsatellites）在新型冠状病毒（SARS-CoV-2）的基因组表达调控、种群遗传进化以及宿主免疫互作调节方面发挥重要作用。该研究利用NCBI数据库以及微卫星分析系统筛选并测试SARS-CoV-2原株及变体中不同微卫星数量与遗传特征的关联，探索影响SARS-CoV-2遗传多样性的微卫星特征。通过生物信息学分析，构建SARS-CoV-2的全基因组序列库，并收集关于序列库的遗传特征、微卫星数量以及微卫星相对位置分布特征信息；通过生物统计学分析，对不同微卫星数量进行相关性测试以及单样本Wilcoxon符号秩非参数检验。结果表明，SARS-CoV-2的原株与变体（除Lambda和Omicron）中不同微卫星数量、占比与相对位置分布特征相似。2核苷酸重复（77%～78%）、3次基序重复（22%～23%）以及全长6 bp（73%）的微卫星占比较高，而ORF3a（0.48/100 bp）、E（0.44/100 bp）与N（0.40/100 bp）3个编码区序列的微卫星密度也较高。总平均微卫星数量与碱基含量间存在显著的负相关性（r：–0.799 6；P：0.009 7），但与碱基替换量无显著相关性。本研究丰富了分子生物学领域对SARS-CoV-2的遗传多样性以及进化机制的研究，并为新型冠状病毒感染疫情的防治提供了新思路。
关键词：新型冠状病毒；微卫星；遗传多样性；碱基含量偏向性；种群遗传进化
中图分类号：R373                               文献标志码：A                              DOI：10.3969/j.issn.1007-7146.2023.03.003

Abstract: Microsatellites were crucial in the control of SARS-CoV-2 genomic expression, population genetic evolution and host immunity interaction. The NCBI database and microsatellite analysis systems were utilized in this study to screen and test the correlation between the number of different microsatellites and genetic characteristics in the original strain and variants of SARS-CoV-2, as well as to investigate the microsatellite features affecting the genetic diversity of SARS-CoV-2. By bioinformatics analysis, the whole-genome sequence database of SARS-CoV-2 was constructed, and information on the genetic characteristics, microsatellite numbers and relative position distribution characteristics of microsatellites in the sequence database were collected; correlation analysis between the number of various microsatellites and one-sample Wilcoxon signed-rank non-parametric tests were performed by biostatistical analysis. The findings revealed that the quantity, proportion, and relative distributing features of various microsatellites in the original strain and SARS-CoV-2 variants (except Lambda and Omicron) were comparable. The proportion of microsatellites with 2 nucleotide repeats (77%～78%), 3 motif repeats (22%～23%), and 6 bp full-length (73%) were relatively high, and the microsatellite density of ORF3a (0.48/100 bp), E (0.44/100 bp), and N (0.40/100 bp) coding regions were also high. The total average number of microsatellites was negatively correlated with the base content (r: –0.799 6, P: 0.009 7), whereas no significant correlation with the number of base substitutions. This study enriched the research on the genetic diversity as well as the evolutionary mechanism of SARS-CoV-2 in the field of molecular biology and provided new ideas for the prevention and control of the corona virus disease 2019 pandemic.
Key words: SARS-CoV-2; microsatellites; genetic diversity; base content bias; population genetic evolution
（Acta Laser Biology Sinica, 2023, 32(3): 208-216）