Abstract
BackgroundThe human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte. These antigens elicit a strain-specific antibody response that is associated with protection from disease. During clonal expansion of blood-stage parasites, the surface phenotype of the infected erythrocyte changes because of transcriptional switching among the 40 to 50 members of the highly polymorphic var multi-gene family which encode PfEMP1 variants. Studies to date have compared var repertoires of natural isolates from various geographical locations but have not addressed any within-population structure that may exist among repertoires.MethodsDistinct parasite genotypes from a single population co-circulating among a defined group of hosts were selected. PCR products encoding the DBL-α domain of PfEMP-1 were cloned and sequenced from each of three isolates. Repertoire similarity was statistically evaluated using combinatorial analysis. The chromosomal location of shared sequences was inferred from similarity to dbl-α of known location in the 3D7 genome.ResultsSympatric parasites were found to share few var gene sequences, even when alleles at other polymorphic loci were shared. A number of the sequences shared by at least two of the isolates studied were found to be related to 3D7 genomic sequences with non-telomeric chromosomal locations, or atypical domain structures, which may represent globally conserved loci.ConclusionThe parasite population studied is structured, with minimal overlap in PfEMP1 repertoires. The var gene family accumulates diversity more rapidly than other antigen genes examined. This may be facilitated by ectopic recombination among the sub-telomeric regions of P. falciparum chromosomes.
Highlights
The human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte
Human erythrocytes infected with certain life-cycle stages of the malaria parasite Plasmodium falciparum express on their surface a family of parasite-encoded adhesins known collectively as PfEMP1, encoded by 40 to 50 members of the var multi-gene family [1]
The amino-terminal Duffy-binding like" (DBL)-α is the most common extra-cellular domain, occurring in all but a handful of PfEMP1 polypeptide sequences predicted to date [2,3]. var sequence similarity does not necessarily indicate shared geographic origin, and substantial dbl-α sequence polymorphism is found at the genomic level among parasite isolates both within and among endemic areas [6,7]
Summary
The human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte. These antigens elicit a strain-specific antibody response that is associated with protection from disease. The parasite evades the host immune response against PfEMP1 by clonal switching of transcription among var genes encoding the variants on the erythrocyte surface This process of antigenic variation extends the duration of infection with any particular P. falciparum genotype, as a small proportion of each new generation of progeny expresses novel surface phenotypes not recognised by concurrent anti-PfEMP1 antibodies
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