A comparative study of erythrocyte binding like 1 gene sequences among plasmodium falciparum isolates from two malaria endemic sites in Kenya.
Gichemi, Grace Njoki
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Members of the Duffy binding like erythrocyte binding-protein (DBL-EBP) family represent some of the merozoite proteins involved in invasion of the erythrocyte; they bind with high affinity to glycophorins on the surface of erythrocytes. At present, five members of the DBL- EBP family have been identified in the P. falciparum genome, based on gene structure and amino acid sequence homology. Several studies, on both field isolates and laboratory strains have examined the level of polymorphism in several members of the EBP family: EBA-175, EBA-140 and EBA-165 in region II and Duffy binding protein region II in P. falciparum and P. vivax respectively. EBA are prime malaria vaccine candidates and antigenic diversity within populations is one of the main factors limiting efficacy of any asexual -stage vaccine including one based on ebl-l. In this study DNA coding for ebl-l antigen was isolated in 53 isolates from Tiwi and Mbita which are malaria endemic regions in Kenya. Nested peR using published primer sequences (Genebank) was used to amplify the region one of ebl-l gene. The amplicons were purified and nucleotide sequences obtained. Neutrality test was applied to these sequences (Mbita D=0.06353, Tiwi D=0.00355 and Ka/Ks ratio of 0.14494 in Mbita, 0.18634 in Tiwi) which provided evidence of significant difference in selective pressure operating on the sequences of ebl-l domain from the two regions. This is consistent with ebl-l being a target of protective immunity. Similarly a peculiar pattern of regional diversity (mean nucleotide diversity, 0.258 Tiwi and 0.287 Mbita) and particular substitutions (substitution of amino acid glutamine with stop codon in coding region) found were suggestive of strong constraints acting on evolution of ebl-l at the population level. The information yielded by this study has implication for the design and assessment of EBP based vaccines.