Large deletions result from breakage and healing of P. falciparum chromosomes

The human malaria parasite P. falciparum exhibits extensive strain-dependent chromosomal polymorphisms that have been implicated in the generation of antigenic variability in this organism. These polymorphisms can result in large deletions in chromosomes as determined by pulsed-field gradient gel electrophoresis. We have investigated the molecular basis for extensive deletions in chromosomes 2 and 8 in multiple geographic isolates of this parasite that result in the loss of expression of well-characterized parasite antigens. The structure of these polymorphic chromosomes reveal that a mechanism of chromosome breakage and healing by the addition of telomeric repeats most plausibly accounts for these karyotypes. Furthermore, the orientation of these gene fragments on their truncated chromosomes reveal that the healed chromosome originally associated with centromeric elements is mitotically stable and maintained. A model for the possible role of this mechanism in the complex parasite life-cycle is discussed.