Sympatric Plasmodium falciparum isolates from Venezuela have structured var gene repertoires.
BACKGROUND
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. 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.


METHODS
Distinct parasite genotypes from a single population co-circulating among a defined group of hosts were selected. PCR products encoding the DBL-alpha 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-alpha of known location in the 3D7 genome.


RESULTS
Sympatric 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.


CONCLUSIONS
The 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.
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London, WC1E 7HT, UK. adriana.tami@lshtm.ac.uk
Adriana
A
Tami
Rosalynn
R
Ord
Geoffrey A T
GA
Targett
Colin J
CJ
Sutherland
D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D017125:Genes, Protozoan; D014644:Genetic Variation; D005828:Genetics, Population / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification*; D017434:Protein Structure, Tertiary / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics; D014687:Venezuela / Q000453:epidemiology
D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C072492:glutamate-rich protein, Plasmodium