Diversifying Selection on the Thrombospondin-Related Adhesive Protein (TRAP) Gene of Plasmodium falciparum in Thailand

• Published in: PloS one Vol. 9; no. 2; p. e90522
• Main Authors: Ohashi, Jun, Suzuki, Yuji, Naka, Izumi, Hananantachai, Hathairad, Patarapotikul, Jintana
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.02.2014; Public Library of Science (PLoS)
• Subjects: Adhesives; Amino Acid Sequence; Amino acids; Analysis; Anopheles; Antigens; Aquatic insects; Biology; Control; Cytotoxicity; Deoxyribonucleic acid; DNA; Epidemiology; Erythrocytes; Erythrocytes - immunology; Erythrocytes - parasitology; Evolution; Gene Frequency; Genes; Genetic aspects; Genetic testing; Genetic Variation - immunology; Genotype; Gliding; Hepatocytes; Hepatocytes - immunology; Hepatocytes - parasitology; Host-Parasite Interactions - immunology; Human behavior; Humans; Immune response; Immune system; Immunology; Integrated software; Malaria; Malaria, Falciparum - immunology; Malaria, Falciparum - parasitology; Medicine; Molecular evolution; Molecular Sequence Data; Mosquitoes; Mutation; Phylogeny; Plasmodium; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - immunology; Plasmodium falciparum - physiology; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Polymorphism, Single Nucleotide - immunology; Population genetics; Population studies; Positive selection; Proteins; Protozoan Proteins - classification; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Selection, Genetic - immunology; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Sporozoites; Sporozoites - immunology; Sporozoites - metabolism; Substitutes; Thailand; Thrombospondin; Thrombospondin-related adhesive protein; Trap gene; Thailand; Bangkok Thailand
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090522

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.