PMID- 24587387 OWN - NLM STAT- MEDLINE DCOM- 20150626 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 2 DP - 2014 TI - Diversifying selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum in Thailand. PG - e90522 LID - 10.1371/journal.pone.0090522 [doi] LID - e90522 AB - 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. FAU - Ohashi, Jun AU - Ohashi J AD - Molecular and Genetic Epidemiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. FAU - Suzuki, Yuji AU - Suzuki Y AD - Molecular and Genetic Epidemiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. FAU - Naka, Izumi AU - Naka I AD - Molecular and Genetic Epidemiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. FAU - Hananantachai, Hathairad AU - Hananantachai H AD - Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. FAU - Patarapotikul, Jintana AU - Patarapotikul J AD - Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140228 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Protozoan Proteins) RN - 120300-02-9 (thrombospondin-related adhesive protein, protozoan) SB - IM MH - Amino Acid Sequence MH - Erythrocytes/immunology/parasitology MH - Gene Frequency MH - Genetic Variation/immunology MH - Genotype MH - Hepatocytes/immunology/parasitology MH - Host-Parasite Interactions/immunology MH - Humans MH - Malaria, Falciparum/*immunology/parasitology MH - Molecular Sequence Data MH - Phylogeny MH - Plasmodium falciparum/genetics/*immunology/physiology MH - Polymerase Chain Reaction MH - Polymorphism, Single Nucleotide/genetics/*immunology MH - Protozoan Proteins/classification/genetics/*immunology MH - Selection, Genetic/immunology MH - Sequence Analysis, DNA MH - Sequence Homology, Amino Acid MH - Sporozoites/immunology/metabolism MH - Thailand PMC - PMC3938765 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/03/04 06:00 MHDA- 2015/06/27 06:00 PMCR- 2014/02/28 CRDT- 2014/03/04 06:00 PHST- 2013/08/30 00:00 [received] PHST- 2014/02/02 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2015/06/27 06:00 [medline] PHST- 2014/02/28 00:00 [pmc-release] AID - PONE-D-13-35800 [pii] AID - 10.1371/journal.pone.0090522 [doi] PST - epublish SO - PLoS One. 2014 Feb 28;9(2):e90522. doi: 10.1371/journal.pone.0090522. eCollection 2014.