Plasmodium falciparum: Chloroquine selection of a cloned line and DNA rearrangements

The chloroquine sensitive Plasmodium falciparum clone, HB3, was selected for growth in increasing amounts of chloroquine. Increases in the size of chromosome 3 were observed with increased chloroquine selection, with the less chloroquine-sensitive parasites possessing the larger forms of the chromosome. Removal of chloroquine selection resulted in a decrease in size of the larger form to the original size and reexposure of these parasites to chloroquine selected again for parasites with a larger chromosome 3. These results suggest that the increase in size of chromosome 3 was associated with the decreased drug sensitivity in the chloroquine selected parasites. A macrorestriction map of chromosome 3 was constructed using the parent HB3 and drug selected lines. The chromosomal size increase was found to have resulted from DNA amplification occurring in 100-kb amplicons. Other isolates of P. falciparum were screened for large size polymorphism in chromosome 3 to determine if chromosome amplification events in this area of the genome also occurred in field isolates. No size changes-that correlated with the amplified region in the chloroquine selected lines were observed. (C) 1996 Academic Press, Inc.