Mutation analysis of 20 SARS virus genome sequences: evidence for negative selection in replicase ORF1b and spike gene  

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(英文)

作　　者：胡兰靛 郑广勇 江海松 夏煜 张艺 孔祥银 

机构地区：[1]中国科学院上海生命科学研究院上海第二医科大学健康科学中心,上海200025

出　　处：《Acta Pharmacologica Sinica》2003年第8期741-745,共5页中国药理学报（英文版）

基　　金：Project supported by National High Technology "863" Programs of China;National Natural Science Foundation of China;National Science Fund for Distinguished Young Scholars, State Key Technologies R&D programme (973).

摘　　要：AIM: Recently, more SARS-CoV virus genome sequences are released to the GenBank database. The aim of this study 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 of non-synonymous nucleotide substitution per non-synonymous site (K_a) and synonymous nucleotide substitution per synonymous site (K_s) for SARS-CoV virus genes. RESULTS: The K_a/K_s ratios for replicase polyprotein ORF1a, ORF1b, 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 ORF1b is undergoing negative selection; negative selection force is also probably operating on spike protein gene. These results provide basis for future developing a new drug and vaccine against SARS.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(K_a)和同义突变频率(K_s)之比。结果:复制酶ORE1a,ORF1b和spike蛋白基因的K_a/K_S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。

关 键 词：severe acute respiratory syndrome SARS-CoV virus negative selection replicase polyprotein spike protein 

分 类 号：R346[医药卫生—基础医学]