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Size polymorphism and low sequence diversity in the locus encoding the Plasmodium vivax rhoptry neck protein 4 (PvRON4) in Colombian isolates

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Buitrago, Sindy P.
Garzón-Ospina, Diego
Patarroyo, Manuel A.

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2016

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BioMed Central Ltd.

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Abstract
Background: Designing a vaccine against Plasmodium vivax has focused on selecting antigens involved in invasion mechanisms that must have domains with low polymorphism for avoiding allele-specific immune responses. The rhoptry neck protein 4 (RON4) forms part of the tight junction, which is essential in the invasion of hepatocytes and/or erythrocytes; however, little is known about this locus’ genetic diversity. Methods: DNA sequences from 73 Colombian clinical isolates from pvron4 gene were analysed for characterizing their genetic diversity; pvron4 haplotype number and distribution, as well as the evolutionary forces determining diversity pattern, were assessed by population genetics and molecular evolutionary approaches. Results: ron4 has low genetic diversity in P. vivax at sequence level; however, a variable amount of tandem repeats at the N-terminal region leads to extensive size polymorphism. This region seems to be exposed to the immune system. The central region has a putative esterase/lipase domain which, like the protein’s C-terminal fragment, is highly conserved at intra- and inter-species level. Both regions are under purifying selection. Conclusions: pvron4 is the locus having the lowest genetic diversity described to date for P. vivax. The repeat regions in the N-terminal region could be associated with immune evasion mechanisms while the central region and the C-terminal region seem to be under functional or structural constraint. Bearing such results in mind, the PvRON4 central and/or C-terminal portions represent promising candidates when designing a subunit-based vaccine as they are aimed at avoiding an allele-specific immune response, which might limit vaccine efficacy. © 2016 The Author(s).
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Esterase , molecular , Tight junction protein , Triacylglycerol lipase , Unclassified drug , Protozoal dna , Protozoal protein , Amino terminal sequence , Article , Carboxy terminal sequence , Colombia , Controlled study , Dna sequence , Gene , Genetic conservation , Genetic polymorphism , Genetic variability , Immune system , Nonhuman , Plasmodium vivax , Purifying selection , Pvron4 gene , Tandem repeat , Adolescent , Adult , Chemistry , Cluster analysis , Female , Genetic variation , Genetics , Haplotype , Human , Isolation and purification , Male , Middle aged , Molecular evolution , Parasitology , Phylogeny , Plasmodium vivax , Plasmodium vivax malaria , Sequence homology , Young adult , Adolescent , Adult , Cluster analysis , Colombia , Dna , Evolution , Female , Genetic variation , Haplotypes , Humans , Malaria , Male , Middle aged , Phylogeny , Plasmodium vivax , Protozoan proteins , Sequence analysis , Sequence homology , Young adult , Functional restriction , Genetic diversity , Natural selection , Plasmodium vivax , Pvron4 , Rhoptry , Tandem repeat
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