Limits...
Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates.

Kosaisavee V, Lek-Uthai U, Suwanarusk R, Grüner AC, Russell B, Nosten F, Rénia L, Snounou G - PLoS ONE (2012)

Bottom Line: It had been previously found that Pvrbp2c is substantially more polymorphic than Pvrbp1.Although the degree of polymorphism exhibited by these two genes was higher than that of Pvrbp1, it did not reach the exceptional diversity noted for Pvrbp2c.Our data also shows that there are highly conserved regions in rbp2a and rbp2b, which might provide suitable targets for future vaccine development against the blood stage of P. vivax.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.

ABSTRACT

Background: Plasmodium vivax merozoites specifically invade reticulocytes. Until recently, two reticulocyte-binding proteins (Pvrbp1 and Pvrbp2) expressed at the apical pole of the P. vivax merozoite were considered to be involved in reticulocyte recognition. The genome sequence recently obtained for the Salvador I (Sal-I) strain of P. vivax revealed additional genes in this family, and in particular Pvrbp2a, Pvrbp2b (Pvrbp2 has been renamed as Pvrbp2c) and two pseudogenes Pvrbp2d and Pvrbp3. It had been previously found that Pvrbp2c is substantially more polymorphic than Pvrbp1. The primary goal of this study was to ascertain the level of polymorphism of these new genes.

Methodology/principal findings: The sequence of the Pvrbp2a, Pvrbp2b, Pvrbp2d and Pvrbp3 genes were obtained by amplification/cloning using DNA purified from four isolates collected from patients that acquired the infection in the four cardinal regions of Thailand (west, north, south and east). An additional seven isolates from western Thailand were analyzed for gene copy number variation. There were significant polymorphisms exhibited by these genes (compared to the reference Sal-I strain) with the ratio of mutations leading to a non-synonymous or synonymous amino acid change close to 3∶1 for Pvrbp2a and Pvrbp2b. Although the degree of polymorphism exhibited by these two genes was higher than that of Pvrbp1, it did not reach the exceptional diversity noted for Pvrbp2c. It was interesting to note that variations in the copy number of Pvrbp2a and Pvrbp2b occurred in some isolates.

Conclusions/significance: The evolution of different members of the Pvrbp2 family and their relatively high degree of polymorphism suggests that the proteins encoded by these genes are important for parasite survival and are under immune selection. Our data also shows that there are highly conserved regions in rbp2a and rbp2b, which might provide suitable targets for future vaccine development against the blood stage of P. vivax.

Show MeSH

Related in: MedlinePlus

The copy number of Pvrbp2a, Pvrbp2b genes in seven P. vivax isolates (Numbered TK1 to TK7) collected in western Thailand (Tak province).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3293883&req=5

pone-0032105-g003: The copy number of Pvrbp2a, Pvrbp2b genes in seven P. vivax isolates (Numbered TK1 to TK7) collected in western Thailand (Tak province).

Mentions: It had been previously noted that some P. falciparum lines harbour multiple copies of one of the Pvrbp homologues, Pfrh1[25]. Variation in the copy number of Pvrbp2a and Pvrbp2b were sought in seven isolates collected from west Thailand (Tak province), and this was found in two of these P. vivax isolates: there were two copies of Pvrbp2b in one, and there were two copies of both Pvrbp2a and Pvrbp2b in the other (Fig. 3). The functional significance, if any, of these copy number variations is not known at present. This would also require a survey of a larger number of P. vivax isolates, and ultimately a means to ascertain if there is a link between the number of Pvrbp copy number and a particular parasite phenotype. Nonetheless, one could speculate that the pseudogenes (Pvrbp2d and Pvrbp3) might have been derived from genes present as multiple copies. It should be confirmed that Pvrbp2d and Pvrbp3 are indeed true pseudogenes. For example, evidence for the protein encoded by one of the homologues of the Pvrbp genes in P. falciparum (Pfrh3) that was considered to be a pseudogene, was detected by proteomic analysis in sporozoites extracts [26].


Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates.

Kosaisavee V, Lek-Uthai U, Suwanarusk R, Grüner AC, Russell B, Nosten F, Rénia L, Snounou G - PLoS ONE (2012)

The copy number of Pvrbp2a, Pvrbp2b genes in seven P. vivax isolates (Numbered TK1 to TK7) collected in western Thailand (Tak province).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293883&req=5

pone-0032105-g003: The copy number of Pvrbp2a, Pvrbp2b genes in seven P. vivax isolates (Numbered TK1 to TK7) collected in western Thailand (Tak province).
Mentions: It had been previously noted that some P. falciparum lines harbour multiple copies of one of the Pvrbp homologues, Pfrh1[25]. Variation in the copy number of Pvrbp2a and Pvrbp2b were sought in seven isolates collected from west Thailand (Tak province), and this was found in two of these P. vivax isolates: there were two copies of Pvrbp2b in one, and there were two copies of both Pvrbp2a and Pvrbp2b in the other (Fig. 3). The functional significance, if any, of these copy number variations is not known at present. This would also require a survey of a larger number of P. vivax isolates, and ultimately a means to ascertain if there is a link between the number of Pvrbp copy number and a particular parasite phenotype. Nonetheless, one could speculate that the pseudogenes (Pvrbp2d and Pvrbp3) might have been derived from genes present as multiple copies. It should be confirmed that Pvrbp2d and Pvrbp3 are indeed true pseudogenes. For example, evidence for the protein encoded by one of the homologues of the Pvrbp genes in P. falciparum (Pfrh3) that was considered to be a pseudogene, was detected by proteomic analysis in sporozoites extracts [26].

Bottom Line: It had been previously found that Pvrbp2c is substantially more polymorphic than Pvrbp1.Although the degree of polymorphism exhibited by these two genes was higher than that of Pvrbp1, it did not reach the exceptional diversity noted for Pvrbp2c.Our data also shows that there are highly conserved regions in rbp2a and rbp2b, which might provide suitable targets for future vaccine development against the blood stage of P. vivax.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.

ABSTRACT

Background: Plasmodium vivax merozoites specifically invade reticulocytes. Until recently, two reticulocyte-binding proteins (Pvrbp1 and Pvrbp2) expressed at the apical pole of the P. vivax merozoite were considered to be involved in reticulocyte recognition. The genome sequence recently obtained for the Salvador I (Sal-I) strain of P. vivax revealed additional genes in this family, and in particular Pvrbp2a, Pvrbp2b (Pvrbp2 has been renamed as Pvrbp2c) and two pseudogenes Pvrbp2d and Pvrbp3. It had been previously found that Pvrbp2c is substantially more polymorphic than Pvrbp1. The primary goal of this study was to ascertain the level of polymorphism of these new genes.

Methodology/principal findings: The sequence of the Pvrbp2a, Pvrbp2b, Pvrbp2d and Pvrbp3 genes were obtained by amplification/cloning using DNA purified from four isolates collected from patients that acquired the infection in the four cardinal regions of Thailand (west, north, south and east). An additional seven isolates from western Thailand were analyzed for gene copy number variation. There were significant polymorphisms exhibited by these genes (compared to the reference Sal-I strain) with the ratio of mutations leading to a non-synonymous or synonymous amino acid change close to 3∶1 for Pvrbp2a and Pvrbp2b. Although the degree of polymorphism exhibited by these two genes was higher than that of Pvrbp1, it did not reach the exceptional diversity noted for Pvrbp2c. It was interesting to note that variations in the copy number of Pvrbp2a and Pvrbp2b occurred in some isolates.

Conclusions/significance: The evolution of different members of the Pvrbp2 family and their relatively high degree of polymorphism suggests that the proteins encoded by these genes are important for parasite survival and are under immune selection. Our data also shows that there are highly conserved regions in rbp2a and rbp2b, which might provide suitable targets for future vaccine development against the blood stage of P. vivax.

Show MeSH
Related in: MedlinePlus