Population genetic structure of domain I of apical membrane antigen-1 in Plasmodium falciparum isolates from Hazara division of Pakistan

Abstract

BackgroundThe Plasmodium falciparum apical membrane antigen-1 (PfAMA1) is considered as an ideal vaccine candidate for malaria control due to its high level of immunogenicity and essential role in parasite survival. Among the three domains of PfAMA1 protein, hyper-variable region (HVR) of domain I is the most immunogenic. The present study was conducted to evaluate the extent of genetic diversity across HVR domain I of the pfama1 gene in P. falciparum isolates from Hazara division of Pakistan.MethodsThe HVR domain I of the pfama1 was amplified and sequenced from 20 P. falciparum positive cases from Hazara division of Pakistan. The sequences were analysed in context of global population data of P. falciparum from nine malaria endemic countries. The DNA sequence reads quality assessment, reads assembling, sequences alignment/phylogenetic and population genetic analyses were performed using Staden, Lasergene v. 7.1, MEGA7 and DnaSP v.5 software packages respectively.ResultsTotal 14 mutations were found in Pakistani isolates with 12 parsimony informative sites. During comparison with global isolates, a novel non-synonymous mutation (Y240F) was found specifically in a single Pakistani sample with 5% frequency. The less number of mutations, haplotypes, recombination and low pairwise nucleotide differences revealed tightly linked uniform genetic structure with low genetic diversity at HVR domain I of pfama1 among P. falciparum isolates from Hazara region of Pakistan. This uniform genetic structure may be shaped across Pakistani P. falciparum isolates by bottleneck or natural selection events.ConclusionThe Pakistani P. falciparum isolates were found to maintain a distinct genetic pattern at HVR pfama1 with some extent of genetic relationship with geographically close Myanmar and Indian samples. However, the exact pattern of gene flow and demographic events may infer from whole genome sequence data with large sample size of P. falciparum collected from broad area of Pakistan.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2539-3) contains supplementary material, which is available to authorized users.

Genetic diversity of Plasmodium falciparum AMA-1 antigen from the Northeast Indian state of Tripura and comparison with global sequences: implications for vaccine development

“…In the current study, no unique amino-acid substitutions were observed; all amino-acid substitutions reported here have been observed previously in Tanzania, Ghana, Thailand, Bioko island, Pakistan and some other parts of the world [ 53 , 56 , 57 ]. Of these, the N228K mutation encountered in the current study has been found to be more common in African countries unlike Myanmar and Thailand [ 53 ].…”

Genetic Polymorphism and Natural Selection of Apical Membrane Antigen-1 in Plasmodium falciparum Isolates from Vietnam

“…However, the antibodies induced by AMA-1 recognize either conserved or allele-specific epitopes of AMA-1, resulting in limited protection against distinct alleles [ 15 , 16 , 17 ]. Despite the less variable genetic diversity of AMA-1 compared to other vaccine candidate antigens, such as circumsporozoite protein (CSP), Duffy-binding protein (DBP), and merozoite surface protein-1 (MSP-1), in the global population, it manifests irrefutable polymorphism [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Genetic polymorphism of AMA-1 in global Plasmodium field isolates, and the resulting variants in different geographic areas, are major hurdles in the development of a global malaria vaccine based on this antigen.…”