EXPRESSED VAR GENES ARE FOUND IN PLASMODIUM-FALCIPARUM SUBTELOMERIC REGIONS

The antigenic variation and cytoadherence of Plasmodium falciparum-inf ected erythrocytes are modulated by a family of variant surface protei ns encoded by the var multigene family. The var genes occur on multipl e chromosomes, often in clusters, and 50 to 150 genes are estimated to be present in the haploid parasite genome. Transcripts from var genes have been previously mapped to internal chromosome positions, but the generality of such assignments and the expression sites and mechanism s that control switches of var gene expression are still in early stag es of investigation. Here we describe investigations of closely relate d var genes that occur in association with repetitive elements near th e telomeres of P. falciparum chromosomes. DNA sequence analysis of one of these genes (FCR3-varT11-1) shows the characteristic two-exon stru cture encoding expected var features, including three variable Duffy b inding-like (DBL) domains, a transmembrane sequence, and a carboxy-ter minal segment thought to anchor the protein product in knobs at the su rface of the parasitized erythrocyte. FCR3-varT11-1 cross-hybridizes w ith var genes located close to the telomeres of many other P. falcipar um chromosomes, including a transcribed gene (FCR3-varT3-1) in chromos ome 3 of the P. falciparum FCR3 line. The relatively high level transc ription from this gene shows that the polymorphic chromosome ends of P . falciparum, which have been proposed to be transcriptionally silent, can be active expression sites for var genes. The pattern of the FCR3 -varT11-1 and FCR3-varT3-1 genes are variable between different P. fal ciparum lines, presumably due to DNA rearrangements. Thus, recombinati on events in subtelomeric DNA may have a role in the expression of nov el var forms.