Natural variation within the principal adhesion domain of the Plasmodium vivax duffy binding protein.
The blood-stage development of malaria parasites is initiated by the invasion of merozoites into susceptible erythrocytes. Specific receptor-ligand interactions must occur for the merozoites to first attach to and then invade erythrocytes. Because the invasion process is essential for the parasite's survival and the merozoite adhesion molecules are exposed on the merozoite surface during invasion, these adhesion molecules are candidates for antibody-dependent malaria vaccines. The Duffy binding protein of Plasmodium vivax belongs to a family of erythrocyte-binding proteins that contain functionally conserved cysteine-rich regions. The amino cysteine-rich regions of these homologous erythrocyte-binding proteins were recently identified for P. vivax, Plasmodium knowlesi, and Plasmodium falciparum as the principal erythrocyte-binding domains (C. Chitnis and L. H. Miller, J. Exp. Med. 180:497-506, 1994, and B. K. L. Sim, C. E. Chitnis, K. Wasniowska, T. J. Hadley, and L. H. Miller, Science 264:1941-1944, 1994). We report that amino acids in this critical ligand domain of the P. vivax Duffy binding protein are hypervariable, but this variability is limited. Hypervariability of the erythrocyte-binding domain suggests that this domain is the target of an effective immune response, but conservation of amino acid substitutions indicates that functional constraints limit this variation. In addition, the amino cysteine-rich region and part of the hydrophilic region immediately following it were the site of repeated homologous recombinations as represented by tandem repeat sequence polymorphisms. Similar polymorphisms have been identified in the same region of the homologous genes of P. falciparum and P. knowlesi, suggesting that there is a common mechanism of recombination or gene conversion that occurs in these Plasmodium genes.
Department of Biological Sciences, University of Notre Dame, Indiana.
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Tsuboi
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Kappe
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al-Yaman
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Prickett
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Alpers
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Adams
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002648:Child; D004375:Duffy Blood-Group System; D017125:Genes, Protozoan / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D010966:Plasmodium vivax / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000235:genetics*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000953:Antigens, Protozoan; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface