title: Plasmodium falciparum: genetic polymorphism in apical membrane antigen-1 gene from Indian isolates.
abstract: A number of stage-specific antigens have been characterized for vaccine development against Plasmodium falciparum malaria. This study presents a comprehensive analysis of the sequence polymorphism in Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) in population samples from the eastern and western parts of India. This is the first study of its kind for the nearly full length PfAMA-1 gene from these regions in India. Our observations confirmed that sequence diversity of PfAMA-1 confines only to point mutations and shows 4-8% variation as compared to the prototypes. As opposed to the previous studies on PfAMA-1, our study revealed a greater degree of polymorphism in the Domain II region of PfAMA-1 protein, though signature for diversifying selection is seen throughout the gene. Our present investigation also indicates a very high degree of variation in the reported T- and B-cell epitopes of PfAMA-1. Few noteworthy and unique observations made in this study are the substitution of Cysteine residues responsible for the disulfide bond structure of the protein and the presence of premature termination after 595 amino acids in 3 of the 13 isolates under consideration. These crucial findings add new perspectives to the future of AMA-1 research and could have major implications in establishing AMA-1 as a vaccine candidate.
authors.affiliation: Biological Sciences Group, Birla Institute of Technology and Science, Centre for Biotechnology, Pilani 333031, Rajasthan, India.
authors.forename: Vidya
authors.initials: V
authors.lastname: Rajesh
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Singamsetti
authors.forename: S
authors.initials: S
authors.lastname: Vidya
authors.forename: M
authors.initials: M
authors.lastname: Gowrishankar
authors.forename: M
authors.initials: M
authors.lastname: Elamaran
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Tripathi
authors.forename: N B
authors.initials: NB
authors.lastname: Radhika
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Kochar
authors.forename: Akash
authors.initials: A
authors.lastname: Ranjan
authors.forename: S K
authors.initials: SK
authors.lastname: Roy
authors.forename: Ashis
authors.initials: A
authors.lastname: Das
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D003545:Cysteine / Q000737:chemistry; D016054:DNA, Protozoan / Q000097:blood / Q000737:chemistry; D019353:Endemic Diseases; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007194:India / Q000453:epidemiology; D017780:Malaria Vaccines / Q000737:chemistry / Q000235:genetics; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D003545:Cysteine