Population genetic structure analysis of thrombospondin-related adhesive protein (TRAP) as a vaccine candidate antigen in worldwide Plasmodium falciparum isolates

摘要

Antigenic diversity is a major concern in malaria vaccine development that requires to be considered in developing a malaria vaccine. Plasmodium falciparum thrombospondin-related adhesive protein (PfTRAP) is a leading malaria vaccine candidate antigen. In the current study, we investigated the level of genetic diversity and natural selection of pftrap sequences in P. falciparum isolates from Iran (n = 47). The gene diversity of Iranian pftrap sequences was also compared to available global pftrap sequences deposited in the GenBank or PlasmoDB databases (n = 220). Comparison of Iranian PfTRAP sequences with T9/96 reference sequence showed the presence of 35 amino acid changes in 32 positions and a limited variation in repeat sequences, leading to 13 distinct haplotypes. The overall nucleotide diversity (pi) for the ectodomain of Iranian pftrap sequences was 0.00444 +/- 0.00043, with the highest diversity in Domain IV. Alignment comparison of global PfTRAP sequences with T9/96 reference sequence indicated 96 amino acid replacements as well as extensive variable repeat sequences (9-23 repeats), which led to 192 haplotypes. Among the global isolates, the lowest nucleotide diversity was detected in French Guianan (0.00428 +/- 0.00163) and Iranian (0.00444 +/- 0.00043) pftrap sequences, and the most variation was observed in domains II and IV in all populations. The dN-dS value displayed the evidence of positive selection due to recombination and immune system pressure. The Fst analysis revealed a gene flow between African populations; however, genetic differentiation observed between Iranian and other populations probably was due to gene flow barriers. Both conserved and variable epitopes were predicted in B- and T-cell epitopes of PfTRAP antigen. The obtained results from this study could be helpful for developing a PfTRAP-based malaria vaccine.