Recent studies on the chromosome structure of Plasmodium falciparum have led to two observations: chromosome breakage occurs frequently in subtelomeric regions and the genes coding for a number of immunodominant parasite proteins are located in these fragile chromosomal segments. Toward understanding the biological significance of these observations, we have been studying the variability of a number of these telomeric 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 positions on chromosomes 1, 2, 11 and 14 in clinical isolates from West African patients, giving rise to new parasite genotypes and gene linkage groups. Cloning and molecular analysis of the newly detected resa-related sequences reveal that two of the members of the family have diverged from the ancestral copy on chromosome 1, while the third member on chromosome 14 is very homologous to the ancestral copy indicating that it arose from a recent translocation event. In the second example, we show that the gbp genes form a dispersed gene family that maps to at least 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 environment. We present a model to explain the duplicative translocation of chromosome termini.