人乙型肝炎病毒包膜蛋白多态性的生物信息学分析及其意义

Large-scale polymorphism analysis of hepatitis B virus envelope protein by bioinformatics

目的构建乙肝病毒生物数据库(Bio-HBV Database),针对HBV包膜蛋白序列进行多态性分析。方法构建Bio-HBV生物数据库获得国际基因序列库中所有完整的包膜蛋白并进行比对,采用信息熵评价序列位点的保守性,结合BLOSUM90评分系统和PAML(phylogenetic analyses by maxi mumlikelihood)软件包寻找选择压力下的异常氨基酸替换模式。结果包膜蛋白中ps35,ps132,s49和s127等氨基酸替换具有高度的统计学意义。此外包膜蛋白内有多个重要区段,直接影响HBV生物学功能。我们对这些区段逐一分析了功能与结构的关系。结论通过Bio-HBV生物数据库,用生物信息学方法不仅验证了已知生物学特性的功能域的保守性,更提出了潜在的可以作为研究切入点的新功能域。

Purpose By using the Bio-HBV database, the polymorphism of HBV envelope protein （HBsAg, Pre-S） was studied by bioinformatics. Methods To analyze the conservation of each amino acid in the sequence of this protein, Shannon entropy was used for evaluation. With the BLOSUM90 scoring matrix and PAML （phylogenetic analyses by maximum likelihood） software package, abnormal amino acid substitution patterns, which reflected specific selective pressure, were searched and identified. Results Within these substitution patterns, ps35, ps132, ps49 and s127 substitutions were found to have highly statistical significance. Multiple functional regions located within the envelope protein were also analyzed with bioinformatics methods. Conclusions Results revealed there was close association between the amino acid conservation and the described functional domains. Besides, based on structural analysis, several domains were predicted to have potential functions, which could be further pursued for their biological implications.