Gene synteny and chloroquine resistance in Plasmodium chabaudi

Chloroquine resistance in the rodent malaria parasite Plasmodium chabaudi has been shown to be caused by a gene on chromosome 11, and is not linked to orthologues of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) or Pgh-1 (pfmdr1) genes. In the current work, the progeny of crosses between chloroquine-resistant and sensitive clones' of R chabaudi have been analysed for the inheritance of 658 AFLP markers. Markers linked to the chloroquine responses of the progeny, including two which are completely linked, have been genetically mapped, sequenced and their homologues, or closely linked loci, identified in P. falciparum. The chromosome 11 markers most closely linked to chloroquine resistance in R chabaudi map to loci which are also closely linked in R falciparum, although in two linkage groups on chromosomes 6 and 13 of this species. The P. falciparum orthologue of the gene conferring chloroquine resistance in R chabaudi is predicted to lie within a 250 kb region of P. falciparum chromosome 6, containing approximately 50 genes. The genetic order of the markers in P. chabaudi is co-linear with the physical linkage represented in the P. falciparum genome database. The findings provide evidence for extensive conservation of synteny between the two species. (C) 2004 Elsevier B.V. All rights reserved.