EXPRESSION OF VAR GENES LOCATED WITHIN POLYMORPHIC SUBTELOMERIC DOMAINS OF PLASMODIUM-FALCIPARUM CHROMOSOMES

Plasmodium falciparum var genes encode a diverse family of proteins, l ocated on the surfaces of infected erythrocytes, which are implicated in the pathology of human malaria through antigenic variation and adhe sion of infected erythrocytes to the microvasculature, We have constru cted a complete representative telomere-to telomere yeast artificial c hromosome (YAC) contig map of the P. falciparum chromosome 8 for studi es on the chromosomal organization, distribution, and expression of va r genes. Three var gene loci were identified on chromosome 8, two of w hich map close to the telomeres at either end of the chromosome. Analy sis of the previously described chromosome 2 contig map and random P, falciparum telomeric YAC clones revealed that most, if not all, 14 P. falciparum chromosomes contain var genes in a subtelomeric location, M apping the chromosomal location of vat genes expressed in a long-term culture of the P, falciparum isolate Dd2 revealed that four of the fiv e different expressed var genes identified map within subtelomeric loc ations. Expression of var genes from a chromosomal domain known for fr equent rearrangements has important implications for the mechanism of var gene switching and the generation of novel antigenic and adhesive phenotypes.