COMPARTMENTALIZATION OF GENES-CODING FOR IMMUNODOMINANT ANTIGENS TO FRAGILE CHROMOSOME ENDS LEADS TO DISPERSED SUBTELOMERIC GENE FAMILIES AND RAPID GENE EVOLUTION IN PLASMODIUM-FALCIPARUM

Recent studies on the chromosome structure of Plasmodium falciparum ha ve led to two observations: chromosome breakage occurs frequently in s ubtelomeric regions and the genes coding for a number of immunodominan t parasite proteins are located in these fragile chromosomal segments. Toward understanding the biological significance of these observation s, we have been studying the variability of a number of these telomeri c genes in parasite lines isolated in different regions of the world. In this report, we present evidence that the telomeric location of the resa and the gbp genes of P. falciparum has allowed their dispersion to other chromosomes and eventual alteration. In the first example it is shown that the resa gene has been dispersed to subtelomeric positio ns on chromosomes 1, 2, 11 and 14 in clinical isolates from West Afric an patients, giving rise to new parasite genotypes and gene linkage gr oups. Cloning and molecular analysis of the newly detected resa-relate d sequences reveal that two of the members of the family have diverged from the ancestral copy on chromosome 1, while the third member on ch romosome 14 is very homologous to the ancestral copy indicating that i t arose from a recent translocation event. In the second example, we s how that the gbp genes form a dispersed gene family that maps to at le ast three different chromosome extremities. The data suggest that the compartmentalization of P. falciparum antigen genes to the chromosome ends lead to gene families scattered on several chromosome extremities . We propose that the generation of segmental aneuploidy is a specific mechanism of genome adaptation of P. falciparum to its host environme nt. We present a model to explain the duplicative translocation of chr omosome termini.