GENES NECESSARY FOR EXPRESSION OF A VIRULENCE DETERMINANT AND FOR TRANSMISSION OF PLASMODIUM-FALCIPARUM ARE LOCATED ON A 0.3-MEGABASE REGION OF CHROMOSOME-9

Virulence of the buman malaria parasite Plasmodium falciparum is belie ved to relate to adhesion of parasitized erythrocytes to postcapillary venular endothelium (asexual cytoadherence). Transmission of malaria to the mosquito vector involves a switch from asexual to sexual develo pment (gametocytogenesis). Continuous in vitro culture of P. falciparu m frequently results in irreversible loss of asexual cytoadherence and gametocytogenesis. Field isolates and cloned lines differing in expre ssion of these phenotypes were karyotyped by pulse-field gel electroph oresis. This analysis showed that expression of both phenotypes mapped to a 0.3-Mb subtelomeric deletion of chromosome 9. This deletion freq uendy occurs during adaptation of parasite isolates to in vitro cultur e. Parasites with this deletion did not express the variant surface ag glutination phenotype and the putative asexual cytoadherence ligand de signated P. falciparum erythrocyte membrane protein 1, which has recen tly been shown to undergo antigenic variation. The syntenic relationsh ip between asexual cytoadherence and gametocytogenesis suggests that e xpression of these phenotypes is genetically linked. One explanation f or this linkage is that both developmental pathways share a common cyt oadherence mechanism. This proposed biological and genetic linkage bet ween a virulence factor (asexual cytoadherence) and transmissibffity ( gametocytogenesis) would help explain why a high degree of virulence h as evolved and been maintained in falciparum malaria.