SARS-CoV及其他冠状病毒基因组比较分析

The Genome Comparison of SARS-CoV and Other Coronaviruses

对病毒种内和种间基因组的比较分析能获得很多关于病毒起源与演化的信息。对17株SARS-CoV的种内基因组变异分析发现共有137个变异位点,估算出SARS-CoV的突变率为8.04×10^(-3)核苷酸替换/位点/年。变异位点在基因组上的分布不均匀,变异位点最多的是基因组中编码S1蛋白的区域,而在编码依赖于RNA的RNA聚合酶区域中几乎没有变异位点。核苷酸和氨基酸替换的偏性预示变异可能不仅仅是由随机漂变产生。对冠状病毒种间基因组结构比较分析发现,SARS-CoV的基因组结构与IBV很相似;而保守基因系统发育分析表明,SARS-CoV属于冠状病毒的一个新分支,并且与血清型第二组冠状病毒进化关系较近。对其他某些分子特征的分析发现,在不同的方面SARS-CoV和不同组冠状病毒有不同的相似点。进一步对基因组非保守开放阅读框(ORF)的基序(motif)和跨膜区分析发现,各组冠状病毒基因组中位于基因S-E间的非保守ORF可能是同源的,但不是绝对必要的;而IBV和SARS-CoV的基因组中位于基因M-N间ORF可能不是同源的。综合分析SARS-CoV与3组血清型冠状病毒进化关系、宿主分布,以及SARS-CoV和IBV的s2m的进化关系,可以推测SARS-CoV有可能来自禽类。

The genome comparison of inter-species and intra-species can give us much information about the origin and evolution of viruses. There are 137 mutation sites in the 17 genomes of SARS-CoV,and the mutation rate is about 8. 04×10-3 substitution/site/year. The distribution of the segregating sites is not steady, the most variable region appears in S1 protein,and the nucleotide sequence of RNA-dependent RNA polymerase has very few mutation sites. The substitution bias of nucleotide acids and amino acids indicates the non-random drift products. The comparison of genome structures of SARS-CoV and other coronaviruses shows that SARS-CoV and IBV share the same genome structure. Phylogenetic analyses of conserved genes of coronaviruses indicate that SARS-CoV is a new branch of coronaviruses and appears more close to the group Ⅱ coronaviruses. Interestingly,SARS-CoV shares some different features with different groups of coronaviruses. Additional analyses show that the first ORFs between S and E genes of some coronaviruses are transmembrane proteins and share the common motif, indicating the possible common ancestor. From the host distribution of different groups of coronaviruses and the phylogeny of s2m,we can deduce that avian is the probable natural host of SARS-CoV.