Search

Plasmodium vivax merozoite surface protein 4 (PvMSP4) has been considered to be a promising malarial vaccine candidate. The antigenic diversity displayed by parasite populations is one of the main factors limiting the efficacy of asexual-stage anti-malarial vaccine candidates. The present study is the first characterising PvMSP4 polymorphism. P. vivax isolates were collected from endemic areas in Colombia and diversity and selection pattern studies were carried out. Overall conservation in this protein was remarkable. Changes were only found in exons I and II, the former only having single nucleotide polymorphisms (SNPs) whilst the latter showed variations in tandem repeat number caused by exon II slippage. The remaining regions (EGF-like domain, GPI anchor and intron) were completely conserved. Selection and neutrality tests carried out over variant exons indicated negative selective forces acting on them. No evidence of intragenic recombination was found. The strong conservation displayed in this molecule by isolates from geographically different regions (Colombia, Salvador and Thailand) stresses its potential importance as a candidate for a vaccine against P. vivax malaria.

The population of malaria-causing parasites is characterized by great genetic diversity. Knowledge of the polymorphism generation mechanism is a central issue for developing effective vaccines against malaria and understanding the parasite population structure. Plasmodium vivax genetic diversity has been explained in terms of two major factors: natural selection and intragenic recombination. A modular organization was found within P. vivax Duffy binding protein in the present work. Four Colombian isolates have identical sequences to Salvador-1 strain amongst dpb regions III-VI analysed, suggesting a high identity between Central and South American isolates. Geographically clustered sectors, corresponding to cysteine-rich regions (II and VI), show a high sequence diversity that could reflect a possible immune response evasion mechanism; both positive and negative selection were detected in these regions. In contrast, other dbp gene regions display a non-geographical clustering pattern, lower sequence diversity and predominant negative selective pressure. Recombination was homogeneously detected all along the molecule. These findings suggest that diversification vs. homogenizing forces, drive dbp gene evolution and determine its mosaic region organization.