Department of Biology, Faculty of Science, Chualongkorn University, 254 Phayathai Road, Bangkok, 10330, Thailand.
Veterinary Parasitology Research Group, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
Parasit Vectors. 2018 Jan 22;11(1):49. doi: 10.1186/s13071-018-2630-1.
The glutamate-rich protein (GLURP) of the malaria parasite Plasmodium falciparum is a key surface antigen that serves as a component of a clinical vaccine. Moreover, the GLURP gene is also employed routinely as a genetic marker for malarial genotyping in epidemiological studies. While extensive size polymorphisms in GLURP are well recorded, the extent of the sequence diversity of this gene is rarely investigated. The present study aimed to explore the genetic diversity of GLURP in natural populations of P. falciparum.
The polymorphic C-terminal repetitive R2 region of GLURP sequences from 65 P. falciparum isolates in Thailand were generated and combined with the data from 103 worldwide isolates to generate a GLURP database. The collection was comprised of 168 alleles, encoding 105 unique GLURP subtypes, characterized by 18 types of amino acid repeat units (AAU). Of these, 28 GLURP subtypes, formed by 10 AAU types, were detected in P. falciparum in Thailand. Among them, 19 GLURP subtypes and 2 AAU types are described for the first time in the Thai parasite population. The AAU sequences were highly conserved, which is likely due to negative selection. Standard Fst analysis revealed the shared distributions of GLURP types among the P. falciparum populations, providing evidence of gene flow among the different demographic populations.
Sequence diversity causing size variations in GLURP in Thai P. falciparum populations were detected, and caused by non-synonymous substitutions in repeat units and some insertion/deletion of aspartic acid or glutamic acid codons between repeat units. The P. falciparum population structure based on GLURP showed promising implications for the development of GLURP-based vaccines and for monitoring vaccine efficacy.
疟原虫恶性疟原虫的谷氨酸丰富蛋白（GLURP）是一种关键的表面抗原，作为临床疫苗的组成部分。此外，GLURP 基因也常被用作流行病学研究中疟原虫基因分型的遗传标记。虽然 GLURP 存在广泛的大小多态性，但该基因的序列多样性程度很少被研究。本研究旨在探索恶性疟原虫自然种群中 GLURP 的遗传多样性。
从泰国的 65 株恶性疟原虫分离株中产生了 GLURP 序列的多态性 C 端重复 R2 区，并与来自全球的 103 株分离株的数据相结合，生成了 GLURP 数据库。该集合包括 168 个等位基因，编码 105 个独特的 GLURP 亚型，由 18 种氨基酸重复单元（AAU）组成。其中，在泰国恶性疟原虫中检测到 28 种由 10 种 AAU 类型组成的 GLURP 亚型。其中，有 19 种 GLURP 亚型和 2 种 AAU 类型首次在泰国寄生虫种群中发现。AAU 序列高度保守，这可能是由于负选择。标准 Fst 分析显示 GLURP 类型在恶性疟原虫种群中的共享分布，这为不同人群之间的基因流动提供了证据。
在泰国恶性疟原虫种群中检测到 GLURP 序列多样性引起的大小变异，这是由重复单元中的非同义取代和重复单元之间天冬氨酸或谷氨酸密码子的插入/缺失引起的。基于 GLURP 的恶性疟原虫种群结构对 GLURP 疫苗的开发和监测疫苗效果具有重要意义。
