Ohashi Jun, Suzuki Yuji, Naka Izumi, Hananantachai Hathairad, Patarapotikul Jintana
Molecular and Genetic Epidemiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
PLoS One. 2014 Feb 28;9(2):e90522. doi: 10.1371/journal.pone.0090522. eCollection 2014.
Sporozoites of Plasmodium falciparum are transmitted to human hosts by Anopheles mosquitoes. Thrombospondin-related adhesive protein (TRAP) is expressed in sporozoites and plays a crucial role in sporozoite gliding and invasion of human hepatocytes. A previous study showed that the TRAP gene has been subjected to balancing selection in the Gambian P. falciparum population. To further study the molecular evolution of the TRAP gene in Plasmodium falciparum, we investigated TRAP polymorphisms in P. falciparum isolates from Suan Phueng District in Ratchaburi Province, Thailand. The analysis of the entire TRAP coding sequences in 32 isolates identified a total of 39 single nucleotide polymorphisms (SNPs), which comprised 37 nonsynonymous and two synonymous SNPs. McDonald-Kreitman test showed that the ratio of the number of nonsynonymous to synonymous polymorphic sites within P. falciparum was significantly higher than that of the number of nonsynonymous to synonymous fixed sites between P. falciparum and P. reichenowi. Furthermore, the rate of nonsynonymous substitution was significantly higher than that of synonymous substitution within Thai P. falciparum. These results indicate that the TRAP gene has been subject to diversifying selection in the Thai P. falciparum population as well as the Gambian P. falciparum population. Comparison of our P. falciparum isolates with those from another region of Thailand (Tak province, Thailand) revealed that TRAP was highly differentiated between geographically close regions. This rapid diversification seems to reflect strong recent positive selection on TRAP. Our results suggest that the TRAP molecule is a major target of the human immune response to pre-erythrocytic stages of P. falciparum.
恶性疟原虫的子孢子通过按蚊传播给人类宿主。血小板反应蛋白相关黏附蛋白（TRAP）在子孢子中表达，在子孢子滑行和侵入人类肝细胞过程中起关键作用。先前的一项研究表明，TRAP基因在冈比亚恶性疟原虫群体中经历了平衡选择。为了进一步研究恶性疟原虫中TRAP基因的分子进化，我们调查了泰国叻丕府三蓬区恶性疟原虫分离株中的TRAP多态性。对32个分离株的整个TRAP编码序列进行分析，共鉴定出39个单核苷酸多态性（SNP），其中包括37个非同义SNP和2个同义SNP。麦克唐纳-克里特曼检验表明，恶性疟原虫内非同义多态性位点与同义多态性位点的比例显著高于恶性疟原虫与雷氏疟原虫之间非同义固定位点与同义固定位点的比例。此外，泰国恶性疟原虫内非同义替换率显著高于同义替换率。这些结果表明，TRAP基因在泰国恶性疟原虫群体以及冈比亚恶性疟原虫群体中都经历了多样化选择。将我们的恶性疟原虫分离株与泰国另一个地区（泰国达府）的分离株进行比较发现，TRAP在地理上相近的区域之间高度分化。这种快速分化似乎反映了近期对TRAP的强烈正选择。我们的结果表明，TRAP分子是人类对恶性疟原虫红细胞前期免疫反应的主要靶点。
