Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome

One goal in sequencing the Plasmodium falciparum genome, the agent of the most lethal form of malaria, is to discover vaccine and drug targets(1). However, identifying those targets in a genome in which similar to 60% of genes have unknown functions is an enormous challenge. Because the majority of known malaria antigens and drug-resistant genes are highly polymorphic and under various selective pressures(2-6), genome-wide analysis for signatures of selection may lead to discovery of new vaccine and drug candidates. Here we surveyed 3,539 P. falciparum genes (similar to 65% of the predicted genes) for polymorphisms and identified various highly polymorphic loci and genes, some of which encode new antigens that we confirmed using human immune sera. Our collections of genome-wide SNPs (similar to 65% nonsynonymous) and polymorphic microsatellites and indels provide a high-resolution map (one marker per similar to 4 kb) for mapping parasite traits and studying parasite populations. In addition, we report new antigens, providing urgently needed vaccine candidates for disease control.