Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Gene. 2010 May 15;456(1-2):24-35. doi: 10.1016/j.gene.2010.02.007. Epub 2010 Feb 21.
Plasmodium vivax merozoite surface protein-5 (PvMsp-5), a potential vaccine candidate, is encoded by a two-exon single copy gene. We have conducted a comprehensive analysis of PvMsp-5 by sequencing the entire gene of four parasite populations from northwestern Thailand (n=73), southern Thailand (n=53), Indonesia (n=25) and Brazil (n=24), and five isolates from other endemic areas. Results reveal that exon I exhibits a significantly higher level of nucleotide diversity at both synonymous and nonsynonymous sites than exon II (p<0.01). Neutrality tests based on both intraspecific and interspecific nucleotide polymorphism have detected a signature of positive selection in exon I of all populations while substitutions in exon II mainly followed neutral expectation except that three residues in exon II of northwestern Thailand population appear to be positively selected using the Bayes Empirical Bayes method. Short imperfect repeats were identified in exon I at an equivalent region to its orthologue in P. knowlesi, supporting their close genetic relatedness. Significant levels of population subdivision were detected among most populations including those between northwestern and southern Thailand (p<10(-5)), implying absent or minimal gene flow between these populations. Importantly, evidences for intragenic recombination in PvMsp-5 were found in most populations except that from southern Thailand in which haplotype diversity and nucleotide diversity were exceptionally low. Results from Fu and Li's D*, F* and D and F tests suggested that PvMsp-5 of most P. vivax populations have been maintained by balancing selection whereas southern Thailand population could have gone through recent bottleneck events. These findings are concordant with a substantial reduction in the number of P. vivax cases in southern Thailand during the past decade, followed by a very recent population expansion. Therefore, spatio-temporal monitoring of parasite population genetics provides important implications for disease control.
恶性疟原虫裂殖子表面蛋白-5（PvMsp-5）是一种潜在的疫苗候选抗原，由一个两外显子单拷贝基因编码。我们对来自泰国西北部（n=73）、泰国南部（n=53）、印度尼西亚（n=25）和巴西（n=24）的四个寄生虫群体以及来自其他流行地区的五个分离株的整个基因进行了测序，对 PvMsp-5 进行了全面分析。结果表明，外显子 I 在同义和非同义位点都显示出比外显子 II 更高水平的核苷酸多样性（p<0.01）。基于种内和种间核苷酸多态性的中性检验在所有群体的外显子 I 中都检测到了正选择的特征，而外显子 II 的取代主要遵循中性预期，除了泰国西北部群体的外显子 II 中的三个残基似乎是正选择的，使用贝叶斯经验贝叶斯方法。在外显子 I 中鉴定到与 P. knowlesi 同源物相同的区域存在短的不完全重复，支持它们的密切遗传关系。大多数群体都检测到显著的种群亚结构，包括泰国西北部和南部之间的群体（p<10(-5)），表明这些群体之间不存在或很少有基因流。重要的是，除了泰国南部群体之外，在大多数群体中都发现了 PvMsp-5 中的基因内重组证据，在该群体中，单倍型多样性和核苷酸多样性异常低。Fu 和 Li 的 D*、F*、D 和 F 检验结果表明，大多数 P. vivax 群体的 PvMsp-5 受到平衡选择的维持，而泰国南部群体可能经历了最近的瓶颈事件。这些发现与过去十年中泰国南部的间日疟病例数量显著减少一致，随后是最近的人口扩张。因此，寄生虫种群遗传学的时空监测为疾病控制提供了重要意义。
