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.
Highlights
The 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
The present study investigated the extent of genetic polymorphism at hyper-variable region (HVR) domain I of the pfama1 among P. falciparum isolates collected from low malaria endemic Hazara division of Pakistan
Population genetic analyses of Pakistani Hazara (PKH) samples in context of global isolates The nucleotide diversity of HVR loci at pfama1 of PKH P. falciparum isolates were analysed in context of worldwide samples deposited in GenBank
Summary
The 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. In spite of advances in knowledge, the malaria disease continues to cause significant health care burden worldwide [5]. The genetic polymorphisms in these parasite proteins create hurdles in development of effective vaccines [7]. These polymorphisms change the critical epitopes expression and eventually reduce or cause complete loss of vaccine efficacy [8]. Extensive evaluation of genetic variants in these vaccine candidate antigenic proteins in P. falciparum populations from malaria endemic regions is primarily important for an effective and enduring vaccine development
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