Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions

Thomas Lavstsen,Thor G Theander,Anja Tr Jensen,Ali Salanti,David E Arnot

doi:10.1186/1475-2875-2-27

Thomas Lavstsen, Thor G Theander + Show 3 more

Open Access

https://doi.org/10.1186/1475-2875-2-27

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Abstract

BackgroundThe variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors. The sequence diversity and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence.MethodsUsing two tree-building methods we analysed the coding and non-coding sequences of 3D7 var and rif genes as well as var genes of other parasite strains.Resultsvar genes can be sub-grouped into three major groups (group A, B and C) and two intermediate groups B/A and B/C representing transitions between the three major groups. The best defined var group, group A, comprises telomeric genes transcribed towards the telomere encoding PfEMP1s with complex domain structures different from the 4-domain type dominant of groups B and C. Two sequences belonging to the var1 and var2 subfamilies formed independent groups. A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged. This organization appeared to be unique for the group A var genesConclusionThe grouping of var genes implies that var gene recombination preferentially occurs within var gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.

Highlights

The variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors
Malaria Journal 2003, 2 http://www.malariajournal.com/content/2/1/27 which has been associated with cerebral malaria and chondroitin sulfate A (CSA) associated with binding in the placenta and pregnancy-associated malaria (PAM) [8]
Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is a polymorphic family of high molecular weight adhesion antigens expressed on the surface of infected erythrocytes[9]

Summary

Introduction

The variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors. The particular virulence of P. falciparum is partly due to the ability of infected erythrocytes to adhere to a variety of host receptors and avoid splenic clearance[1,2]. Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is a polymorphic family of high molecular weight adhesion antigens expressed on the surface of infected erythrocytes[9]. The accumulation of antibodies against a broad repertoire of PfEMP1s is probably the functional basis for the natural acquisition of immunity to malaria [10,11,12,13]

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