Limited global diversity of the Plasmodium vivax merozoite surface protein 4 gene

Abstract

Merozoite surface proteins (MSPs) of the malaria parasites are major candidates for vaccine development targeting asexual blood stages. However, the diverse antigenic repertoire of these antigens that induce strain-specific protective immunity in human is a major challenge for vaccine design and often determines the efficacy of a vaccine. Here we further assessed the genetic diversity of Plasmodium vivax MSP4 (PvMSP4) protein using 195 parasite samples collected mostly from Thailand, Indonesia and Brazil. Overall, PvMSP4 is highly conserved with only eight amino acid substitutions. The majority of the haplotype diversity was restricted to the two short tetrapeptide repeat arrays in exon 1 and 2, respectively. Selection and neutrality tests indicated that exon 1 and the entire coding region of PvMSP4 were under purifying selection. Despite the limited nucleotide polymorphism of PvMSP4, significant genetic differentiation among the three major parasite populations was detected. Moreover, microgeographical heterogeneity was also evident in the parasite populations from different endemic areas of Thailand.

Genetic Polymorphism of Plasmodium vivax msp1p, a Paralog of Merozoite Surface Protein 1, from Worldwide Isolates

“…These are involved in putative ligandreceptor interactions during erythrocyte invasion by merozoites. 20,21 Thus, the lack of variation in the C-terminus sequence of PvMSP1P, especially the high conservation of the double EGF-like domains, suggests that these regions play an important role in this process.…”

Genetic diversity of the Plasmodium vivax merozoite surface protein-5 locus from diverse geographic origins

“…Intragenic recombination has reportedly been implicated in sequence diversity in other P. vivax surface proteins such as genes encoding the merozoite surface protein-1, thrombospondin-related adhesive protein and apical membrane antigen-1 (Putaporntip et al, 2001; Putaporntip et al, 2002; Putaporntip et al, 2009). Analysis of linkage disequilibrium between parsimony informative sites and estimation of the minimum number of recombination events in the history of the PvMsp-5 gene have supported previous study that intragenic recombination enhances sequence diversity at this locus (Gomez et al, 2006).…”

“…π±S.D. for southern population = 0.00056±0.00013 and for northwestern population = 0.00214±0.00035 (Putaporntip et al, 2009). Consistently, the low nucleotide polymorphism and the negatively significant values of parameters Fu and Li’s D * and F * at the PvMsp-5 locus of population from southern Thailand would suggest the population bottleneck effect.…”

Bottleneck effects on vaccine-candidate antigen diversity of malaria parasites in Thailand

“…The complete nucleotide sequences of P. falciparum csp and msp-2 and of P. vivax msp-1, ama-1 and msp-4 were obtained by using respective forward and reverse primers for each gene as described previously [10, 12, 19, 23, 24]. Sequences of P. falciparum csp and msp-2 from the NW and of P. vivax ama-1, msp-4 and msp-5 from both NW and South were from our previous analyses [10, 12, 19, 24]. The complete 128 nucleotide sequences of Pvmsp-1 were obtained following the methods as previously described [23].…”

“…The excluded repeat regions of P. vivax msp1 corresponded to blocks 2, 6, 8 and 9 as defined by Putaporntip et al [23]. The excluded repeat regions of P. vivax msp4 were repeat array 1 (in exon 1) and repeat array 2 (in exon 2) identified by Putaporntip et al [24]. The excluded region of P. vivax msp5 was the single central charged amino acid residue-rich repeat region [26].…”