Abstract
BackgroundThe Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate antigen. The complete AMA1 protein is comprised of three domains where domain I exhibits high sequence polymorphism and is thus named as the hyper-variable region (HVR). The present study describes the extent of genetic polymorphism and natural selection at domain I of the ama1 gene among Indian P. falciparum isolates.MethodsThe part of the ama1 gene covering domain I was PCR amplified and sequenced from 157 P. falciparum isolates collected from five different geographical regions of India. Statistical and phylogenetic analyses of the sequences were done using DnaSP ver. 4. 10. 9 and MEGA version 3.0 packages.ResultsA total of 57 AMA1 haplotypes were observed among 157 isolates sequenced. Forty-six of these 57 haplotypes are being reported here for the first time. The parasites collected from the high malaria transmission areas (Assam, Orissa, and Andaman and Nicobar Islands) showed more haplotypes (H) and nucleotide diversity π as compared to low malaria transmission areas (Uttar Pradesh and Goa). The comparison of all five Indian P. falciparum subpopulations indicated moderate level of genetic differentiation and limited gene flow (Fixation index ranging from 0.048 to 0.13) between populations. The difference between rates of non-synonymous and synonymous mutations, Tajima's D and McDonald-Kreitman test statistics suggested that the diversity at domain I of the AMA1 antigen is due to positive natural selection. The minimum recombination events were also high indicating the possible role of recombination in generating AMA1 allelic diversity.ConclusionThe level of genetic diversity and diversifying selection were higher in Assam, Orissa, and Andaman and Nicobar Islands populations as compared to Uttar Pradesh and Goa. The amounts of gene flow among these populations were moderate. The data reported here will be valuable for the development of AMA1-based malaria vaccine.
Highlights
The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate antigen
Haplotype diversity and amino acid changes at domain I The nucleotide sequence encoding domain I of the AMA1 was determined from 157 clinical isolates collected from five different geographical regions (Assam, n = 28; Orissa, n = 35; A & N, n = 40; UP, n = 36; and Goa, n = 18) of India with different malaria transmission intensities
The present study shows that domain I of AMA1 among Indian P. falciparum isolates exhibits fairly high allelic diversity that differs from one region to another
Summary
The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate antigen. Several parasite molecules have been tested for their potential as a vaccine candidate antigens [1]. Majority of these antigens are expressed on the parasite's surface or the parasitized erythrocytes. The Plasmodium proteins expressed on the parasite's surface are more exposed to human immune system and have been found to exhibit high antigenic diversity [2]. Genetic polymorphisms in the parasite antigens help them to evade the host's protective immune response but at the same time it hampers the development of an effective vaccine which can contain this disease
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