Genetic diversity and selection at the Plasmodium vivax apical membrane antigen-1 (PvAMA-1) locus in a Sri Lankan population
Genetic diversity and selection at the Plasmodium vivax apical membrane antigen-1 (PvAMA-1) locus in a Sri Lankan population
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DOI：
10.1093/molbev/msm013
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发表时间：
2007-04-01
影响因子：
10.7
通讯作者：
Wirth, Dyann F.
中科院分区：
文献类型：
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作者：
Gunasekera, Anusha M.;Wickramarachchi, Thilan;Wirth, Dyann F.
间日疟原虫顶膜抗原 1 (PvAMA-1) 是一种重要的疟疾候选疫苗。我们使用来自斯里兰卡的单个群体样本首次对整个 PvAMA-1 基因的核苷酸多样性进行了全面分析。与在恶性疟原虫 AMA-1 基因座上观察到的情况相反，多样化选择的特征在 PvAMA-1 的结构域 II 中最为强烈，表明每个物种的不同结构域可能受到不同的选择压力和功能限制。我们还发现重组在该基因座产生单倍型多样性方面发挥着重要作用，即使在斯里兰卡等低流行地区也是如此。将多样性和重组热点映射到蛋白质的 3 维结构模型上表明，分子的一个表面可能特别可能带有用于抗体识别的表位。该表面表现出有限变异性的区域可能被证明是有希望的疫苗目标。
Plasmodium vivax apical membrane antigen 1 (PvAMA-1) is an important malaria vaccine candidate. We present the first comprehensive analysis of nucleotide diversity across the entire PvAMA-1 gene using a single population sample from Sri Lanka. In contrast to what has been observed at the AMA-1 locus of Plasmodium falciparum, the signature of diversifying selection is seen most strongly in Domain II of PvAMA-1, indicating that the different domains in each species may be subject to varying selective pressures and functional constraints. We also find that recombination plays an important role in generating haplotype diversity at this locus, even in a region of low endemicity such as Sri Lanka. Mapping of diversity and recombination hotspots onto a 3-dimensional structural model of the protein indicates that one surface of the molecule may be particularly likely to bear epitopes for antibody recognition. Regions of this surface that show constrained variability may prove to be promising vaccine targets.