2004年SARS-CoV毒株S基因分子进化特征

目的通过对2004年SARS-CoV毒株S基因序列的变异分析,揭示SARS-CoV毒株S基因进化与SARS流行的关系。方法对广东地区2004年2株SARS-CoV毒株S基因进行序列分析,其余15株毒株S基因序列从GenBank检索,采用DNAStar5.0软件,对检索的SARS-CoV的S基因核苷酸序列进行比对和分析;并结合临床资料对变异毒株进行进化速度分析。结果17株毒株中,S基因7个氨基酸位点全部置换,35个氨基酸位点在不同毒株中置换;所有SARS-CoV均通过氨基酸227位点的置换,增加一个糖基化位点。同义进化中,S基因置换速度为1.46×10-6个核苷酸,进化线性回归方程为Y=1.46×10-6X+0.000736,同时通过Ka计算显示S基因进化明显存在选择性压力。2004年17株SARS-CoV毒株可以分为两条进化途径,其中广东地区的人类的GZ0401毒株与果子狸的PC4-115毒株核苷酸同源性达到99.97%,氨基酸同源性为100%。结论冠状病毒S基因的1个糖蛋白位点增加,可能导致人类SARS-CoV毒株出现并SARS流行;2004年果子狸冠状病毒与人类SARS-CoV毒株分子结构类似,可能存在交叉宿主。S基因同义进化速度较流感HA1基因慢4.2倍,但基因进化明显存在选择性压力。

Evolutionary characteristics on S genes of SARS-CoVs in 2004

To reveal the relation between evolution of S genes in SARS-CoVs and epidemic of SARS by means of analyzing the genetic variation of SARS-CoVs in 2004,the S genes of SARS-CoVs(2 in human,10 in HPC) sequenced from Guangdong province were detected and others were collected from GenBank,which were analyzed with DNAstar5.0,and compared with the differences among S genes.The molecular evolution in speed was carried out by way of analyzing the clinical data.There were amino acid substitutions in S gene of all 17 strains in 2004,with 35 amino acid substitutions in different strains,and there was one more glycoprotein domain in No 227 amino acid in entire human SARS-CoVs.In the synonymous variation,the evolutionary rate in S gene was 1.46×10~(-6) and the evolutionay linear regression equation was Y=1.46×10~(-6)X+0.000736.The evolution on s gene remarkably resulted from the selective pressure as showing in Ka value.Seventeen strains in 2004 were evolutionally divided into two ways,in which the homology between human GZ0401 and HPC PC4-115 was 99.97% in nucleotide sequence and 100% in amino acid sequence.Increase of one glycoprotein domain in S gene in SARS-CoV might possibly result in emergence and outbreak of SARS.There exists cross-host in human and HPC between the human SARS-CoV and HPC coronavirus.S gene in the synonymous variation is 4.2 times slower than HA_(1) gene of in fluenza but the selective pressure on S gene significantly exists in biological evolution.