THE VAR GENES OF PLASMODIUM-FALCIPARUM ARE LOCATED IN THE SUBTELOMERIC REGION OF MOST CHROMOSOMES

PfEMP1, a Plasmodium falciparum-encoded protein on the surface of infe cted erythrocytes is a ligand that mediates binding to receptors on en dothelial cells. The PfEMP1 protein, which is encoded by the large var gene family, shows antigenic variation and changes in binding phenoty pe associated with alterations in antigenicity. We have constructed a yeast artificial chromosome contig of chromosome 12 from P.falciparum and show that var genes are arranged in four clusters; two lie amongst repetitive subtelomeric sequences and two occur in the more conserved central region. Analysis of parasite chromosomes by pulsed field gel electrophoresis (PFGE) demonstrates that most contain var genes and tw o-dimensional PFGE has shown that var genes are located at chromosome ends interspersed amongst repetitive sequences present in the subtelom eric complex. Analysis of a var gene located in the subtelomeric regio n of chromosome 12 has shown that it has close homologues at the oppos ite end of the chromosome and in the subtelomeric region of two other chromosomes. This suggests that recombination between heterologous chr omosomes has occurred in the subtelomeric regions of these chromosomes . The subtelomeric location of var genes dispersed amongst repetitive sequences has important implications for generation of antigenic varia nts and novel cytoadherent specificities of this protein. Keywords: Pl asmodium genes