20条SARS病毒全基因组序列的突变分析:负选择作用于复制酶ORF1b和spike基因的证据

摘要

目的:最近,有越来越多的SARS-CoV病毒基因组序列释放到GenBank数据库中.我们这项研究的目的是通过分析病毒基因组的变异揭示病毒的进化规律.方法:我们从GenBank数据库中获得20条SARS-CoV病毒基因组序列,计算病毒基因非同义突变频率(Ka)和同义突变频率(Ks)之比.结果:复制酶ORF1a,ORF1b和Spike蛋白基因的Ka/Ks之比分别是0.94(p=0.4606),0.38(p=0.0074),0.48(p=0.0685).结论:SARS-CoV复制酶ORF1b在宿主体内正在经历负选择;这种负选择的力量可能也作用于Spike基因.这一发现为治疗SARS药物和抗SARS疫苗研制提供了新的基础.%AIM: Recently, more SARS-CoV virus genome sequences are released to the GenBank database. The aim of thisstudy is to reveal the evolution forces of SARS-CoV virus by analyzing the nucleotide mutations in these sequences.METHODS: We obtained 20 SARS-CoV virus genome sequences from NCBI database, and calculated the ratio ofnon-synonymous nucleotide substitution per non-synonymous site (Ka) and synonymous nucleotide substitutionper synonymous site (Ks) for SARS-CoV virus genes. RESULTS: The Ka/Ks ratios for replicase polyprotein ORF 1 a,ORFlb, and spike protein gene are 1.09 (P=0.6501), 0.38 (P=0.0074), 0.65 (P=0.0685) respectively.CONCLUSION: SARS-CoV virus replicase polyprotein ORFlb is undergoing negative selection; negative selectionforce is also probably operating on spike protein gene. These results provide basis for future developing a new drugand vaccine against SARS.