title: The var genes of Plasmodium falciparum are located in the subtelomeric region of most chromosomes.
abstract: PfEMP1, a Plasmodium falciparum-encoded protein on the surface of infected erythrocytes is a ligand that mediates binding to receptors on endothelial cells. The PfEMP1 protein, which is encoded by the large var gene family, shows antigenic variation and changes in binding phenotype 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 two-dimensional PFGE has shown that var genes are located at chromosome ends interspersed amongst repetitive sequences present in the subtelomeric complex. Analysis of a var gene located in the subtelomeric region of chromosome 12 has shown that it has close homologues at the opposite end of the chromosome and in the subtelomeric region of two other chromosomes. This suggests that recombination between heterologous chromosomes 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 variants and novel cytoadherent specificities of this protein.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Melbourne, Victoria, Australia 3050.
authors.forename: J P
authors.initials: JP
authors.lastname: Rubio
authors.forename: J K
authors.initials: JK
authors.lastname: Thompson
authors.forename: A F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast; D015180:Electrophoresis, Gel, Two-Dimensional; D004921:Erythropoietin / Q000235:genetics*; D017125:Genes, Protozoan; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D016615:Telomere
chemical_list: C099963:EPO mimetic peptide 1; D010456:Peptides, Cyclic; D015800:Protozoan Proteins; D004921:Erythropoietin