Population genetics, sequence diversity and selection in the gene encoding the Plasmodium falciparum apical membrane antigen 1 in clinical isolates from the south-east of Iran

Abstract

The Plasmodium falciparum apical membrane antigen1 (AMA1) is a leading malaria vaccine candidate antigen. In the present investigation, for the first time, the almost full length of the ama1 gene covering domain I (DI), DII and DIII was PCR amplified and sequenced in 21 P. falciparum isolates collected from the southeastern parts of Iran. The result showed the low genetic diversity of Iranian PfAMA1 with 11 PfAMA1 haplotypes in which nine out of 11 haplotypes are novel and have been reported for the first time. The Iranian P. falciparum population indicated a moderate level of genetic differentiation. The difference among the rates of non-synonymous and synonymous mutations, Tajima's D and McDonald-Kreitman tests suggested that the diversity at DI is due to positive natural selection. In addition, recombination contributes to the diversity of Iranian PfAMA1 and this is supported by the decline of the linkage disequilibrium index R(2) with increasing the nucleotide distance. The highly polymorphic residues (positions: 187, 197, 200, 230 and 243) were polymorphic; however, most of the SNPs in non-polymorphic residues were conserved except the residue at position 395. Nevertheless, no mutation was found in the DII loop of the Iranian PfAMA1, indicating that it is subjected to purifying selection. In conclusion, the low genetic diversity in PfAMA1 among Iranian isolates supports and provides valuable information for the development of a PfAMA1-based malaria vaccine.