SARS-CoV-2与SARS病毒基因组中密码子使用的比较

Comparative analysis of codon usage in the genomes of SARS-CoV-2 and SARS virus

目的:分析冠状病毒基因中密码子的进化和变异。方法:运用生物信息学方法和生物统计学方法,对新型冠状病毒(SARS-CoV-2)和非典病毒(SARS)基因中密码子使用的偏好性和密码子的上下文关系进行比较分析。结果:两种病毒密码子的使用都存在显著的偏好性(RSCU值的变化为0.10~2.67),且偏好使用的密码子(偏爱密码子)和避免使用的密码子(稀有密码子)基本是一致的;通过相关性分析发现在两种病毒中密码子适应性指数(CAI)与密码子第三位点的GC含量(GC3)呈显著的负相关性,但SARS-CoV-2的负相关性更强(SARS-CoV-2:R^(2)=0.76,P<0.001;SARS:R^(2)=0.48,P<0.001),随着CAI的增大,GC3降低由于CAI是反映基因表达水平的参数,即高表达基因偏好低GC3的同义密码子。比较偏爱密码子和稀有密码子的上下文关系,发现偏爱密码子与稀有密码子各位点的核苷酸组分存在显著差异,这种差异性表现为在密码子不同位点GC和AT的显著区别,反映了GC含量对同义密码子使用偏爱性的约束。结论:SARSCoV-2和SARS病毒基因组GC含量、密码子的上下文关系、密码子各位点核苷酸的组分、基因的表达水平是影响密码子偏爱性的重要因素,研究结果对SARS-CoV-2和SARS病毒基因组的进化和变异的研究具有参考意义。

Objective To analyze the genetic evolution and variation of coronavirus.Methods The codon usage bias and the codon context in the genes of SARS-CoV-2 and SARS virus were compared and analyzed using bioinformatics methods and biometric methods.Results The codon usage bias was observed in the two kinds of virus,with RSCU value varying from 0.10 to 2.67,and the codons preferred(preferred codons)and avoided(rare codons)were basically the same.The correlation analysis showed that the codon adaption index(CAI)was negatively correlated with the GC content at the third site of the codon(GC3)in the two viruses,and that the negative correlation in SARS-CoV-2 was higher than that in SARS(SARS-CoV 2:R^(2)=0.76,P<0.001;SARS:R^(2)=0.48,P<0.001).GC3 decreased with the increase of CAI which reflected the level of gene expression,suggesting highly expressed genes preferred the synonymous codons with low GC3.Though the analysis on the codon context between preferred codons and rare codons,it was found that there were significant differences in the nucleotide composition between preferred codons and rare codons,which were manifested as differences in GC and AT in different codon sites,reflecting the constraints of GC content on the synonymous codon usage bias.Conclusion GC content,codon context,nucleotide composition and gene expression level of SARS-CoV-2 and SARS virus are important factors affecting codon usage bias.The study has reference significance for the study on the genetic evolution and variation of SARS CoV-2 and SARS virus.