Genetic diversity and effect of natural selection at apical membrane antigen-1 (AMA-1) among Iranian Plasmodium vivax isolates. 2014

Ahmad Reza Esmaeili Rastaghi, and Fatemeh Nedaei, and Hossein Nahrevanian, and Nazanin Hoseinkhan
Department of Parasitology, Pasteur Institute or Iran, Tehran, Iran. aresmar40@yahoo.com

Apical membrane antigen-1 (AMA-1) of Plasmodium vivax Grassi et Feletti, 1890 is a promising malaria vaccine candidate. However, antigenic variation is a major problem to design a universal malaria vaccine. Hence, detailed understanding of the pvama-1 gene polymorphism can provide conductive information on this potential vaccine component. Therefore, this study investigated the extent of genetic polymorphisms at domain I (DI), DII and partial DIII of AMA-1 among Iranian P. vivax isolates. Out of 107 blood samples, 92 were analysed based on the quality of the sequencing data. The sequences were classified into 53 haplotypes. Amino acid changes were observed at 31 positions that 17 were located at DI, 11 were at DII and the rest of them (3 positions) were at DIII. Thus, codon polymorphisms at DI were found to be higher than DII. Also, five of these polymorphic codons (D242E, T374P, S389R, Y391F, I395F) were novel and have not been reported yet. Neutrality analysis by using the dN-dS difference (the difference between the rate of non-synonymous and synonymous mutations) showed a negative diversifying selection at DI, DII and across the length of both domains. The potential B-cell epitopes were found in 5 regions of the PvAMA-1 with 10 mutation sites (E145A, K188N, E189N/K/D, K190Q/E, P210S, E227V, D242E, R249H, G253E, K352E), whereas only one mutation (G288E) has been detected in intrinsically unstructured/disordered regions. Fixation index (Fst) estimation between Iranian and Indian isolates (0.0131) indicated a significant low genetic differentiation. Distribution of the polymorphic sites and IURs mapped on a three dimensional structure of PvAMA-1 showed that these regions were located at two opposite faces of the molecule. In conclusion, the results have significant value in the design and development of a malaria vaccine based on this antigen.

UI MeSH Term Description Entries
D007492 Iran A country bordering the Gulf of Oman, the Persian Gulf, and the Caspian Sea, between Iraq and Pakistan. The capital is Tehran. Islamic Republic of Iran
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010802 Phylogeny The relationships of groups of organisms as reflected by their genetic makeup. Community Phylogenetics,Molecular Phylogenetics,Phylogenetic Analyses,Phylogenetic Analysis,Phylogenetic Clustering,Phylogenetic Comparative Analysis,Phylogenetic Comparative Methods,Phylogenetic Distance,Phylogenetic Generalized Least Squares,Phylogenetic Groups,Phylogenetic Incongruence,Phylogenetic Inference,Phylogenetic Networks,Phylogenetic Reconstruction,Phylogenetic Relatedness,Phylogenetic Relationships,Phylogenetic Signal,Phylogenetic Structure,Phylogenetic Tree,Phylogenetic Trees,Phylogenomics,Analyse, Phylogenetic,Analysis, Phylogenetic,Analysis, Phylogenetic Comparative,Clustering, Phylogenetic,Community Phylogenetic,Comparative Analysis, Phylogenetic,Comparative Method, Phylogenetic,Distance, Phylogenetic,Group, Phylogenetic,Incongruence, Phylogenetic,Inference, Phylogenetic,Method, Phylogenetic Comparative,Molecular Phylogenetic,Network, Phylogenetic,Phylogenetic Analyse,Phylogenetic Clusterings,Phylogenetic Comparative Analyses,Phylogenetic Comparative Method,Phylogenetic Distances,Phylogenetic Group,Phylogenetic Incongruences,Phylogenetic Inferences,Phylogenetic Network,Phylogenetic Reconstructions,Phylogenetic Relatednesses,Phylogenetic Relationship,Phylogenetic Signals,Phylogenetic Structures,Phylogenetic, Community,Phylogenetic, Molecular,Phylogenies,Phylogenomic,Reconstruction, Phylogenetic,Relatedness, Phylogenetic,Relationship, Phylogenetic,Signal, Phylogenetic,Structure, Phylogenetic,Tree, Phylogenetic
D010966 Plasmodium vivax A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium vivaxs,vivax, Plasmodium
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000953 Antigens, Protozoan Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered. Protozoan Antigens

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