Diversity and natural selection in Plasmodium vivax Duffy binding protein gene

Abstract

The Plasmodium vivax Duffy binding protein (DBP) binds to the Duffy blood group antigen on the surface of erythrocytes and is essential for invasion. Natural immunity develops to this protein making it an important vaccine candidate. Genetic diversity within and between populations was compared in 100 dbp sequences from isolates obtained from Papua New Guinea, Colombia, and South Korea. The cysteine-rich region II, that contains the binding domain, has the highest diversity compared to the rest of the dbp gene and appears to be under strong selective pressure based on statistical tests comparing rates of non-synonymous (K(n)) to synonymous mutations (K(s)) among P. vivax isolates and to those of closely related species. By contrast, meiotic recombination was not found to be significant for maintaining genetic diversity. A comparison of the patterns of nucleotide diversity within dbpII to that of genes encoding homologous erythrocyte binding proteins of Plasmodium knowlesi predict critical binding residues juxtaposed to polymorphic B- and T-cell epitopes. Phylogenic analysis and measurement of nucleotide diversity between and within the different geographic populations support emergence of distinct allelic families suggestive of divergent selection of alleles between populations. Development of a P. vivax DBP-based vaccine must take into account regions of high diversity within the molecule and alleles that show distinct geographic differences.