Haydon D, Lea S, Fry L, Knowles N, Samuel A R, Stuart D, Woolhouse M E
Pirbright Laboratory, Institute for Animal Health, Woking, United Kingdom.
J Mol Evol. 1998 Apr;46(4):465-75. doi: 10.1007/pl00006327.
The VP1 capsid protein of foot and mouth disease virus (FMDV) is highly polymorphic and contains several of the major immunogenic sites important to effective antibody neutralization and subsequent viral clearance by the immune system. Whether this high level of polymorphism is of adaptive value to the virus remains unknown. In this study we examined sequence data from a set of 55 isolates in order to establish the nature of selective pressures acting on this gene. Using the known molecular structure of VP1, the rates and ratios of different types of nonsynonymous and synonymous changes were compared between different parts of the protein. All parts of the protein are subject to purifying selection, but this is greatest amongst those amino acid residues within beta-strands and is significantly reduced at residues exposed on the capsid surface, which include those residues demonstrated by previous mutational analyses to permit the virus to escape from monoclonal antibody binding. The ratios of nonsynonymous substitution resulting in various forms of physicochemically radical and conserved amino acid change were shown to be largely equal throughout these different parts of the protein. There was a consistently higher level of nonsynonymous and charge radical sites in those regions of the gene coding for residues exposed on the outer surface of the capsid and a marked difference in the use of amino acids between surface and nonsurface regions of the protein. However, the analysis is consistent with the hypothesis that the observed sequence variation arises where it is least likely to be disruptive to the higher-order structure of the protein and is not necessarily due to positive Darwinian selection.
口蹄疫病毒（FMDV）的VP1衣壳蛋白具有高度多态性，包含几个对有效抗体中和及随后免疫系统清除病毒至关重要的主要免疫原性位点。这种高度多态性对病毒是否具有适应性价值仍不清楚。在本研究中，我们检查了一组55个分离株的序列数据，以确定作用于该基因的选择压力的性质。利用VP1已知的分子结构，比较了蛋白质不同部分不同类型非同义突变和同义突变的发生率及比率。蛋白质的所有部分都受到纯化选择，但在β链内的氨基酸残基中这种选择最为强烈，而在衣壳表面暴露的残基处则显著降低，其中包括先前突变分析表明能使病毒逃避单克隆抗体结合的那些残基。在蛋白质的这些不同部分，导致各种形式的物理化学性质激进和保守氨基酸变化的非同义替换比率在很大程度上是相等的。在编码衣壳外表面暴露残基的基因区域中，非同义突变和电荷激进位点的水平始终较高，并且蛋白质的表面和非表面区域在氨基酸使用上存在显著差异。然而，该分析与以下假设一致：观察到的序列变异出现在对蛋白质高阶结构破坏可能性最小的地方，不一定是由于正达尔文选择。
