Genetic Diversity in Plasmodium falciparum

Abstract

This chapter focuses on those forms of genetic diversity that are clearly understood at the deoxyribonucleic acid (DNA) level. The application of recombinant DNA technology to the study of Plasmodium falciparum and other species of Plasmodium has resulted in rapid advances in the understanding of genetic diversity in malaria. Variation in repeat sequences from one isolate to another forms a major component of genetic diversity in Plasmodium. The introduction of pulsed field gradient (PFG) electrophoresis has allowed one to study Plasmodium chromosomes, and there is considerable variation in chromosome size from one parasite clone to another. A major component of this variation appears to be recombinational expansion and contraction of repetitive subtelomeric sequences. As many of the repetitive antigens are also encoded by subtelomeric genes, there is a possible connection between antigenic diversity and chromosome size variation. The results of the first genetic cross between two defined clones of P. falciparum together with the determination of the chromosomal location of many of the genes demonstrate that during the transmission of mixed infections, novel genotypes are generated. The underlying molecular basis for another important form of genetic diversity––namely, resistance to an important antimalarial drug, pyrimethamine––has now been determined. A candidate gene that may underlie resistance to the other major antimalarial drug, chloroquine, can now been cloned. However, before studies at the DNA sequence level, studies using a wide variety of approaches had clearly identified a number of different types of genetic diversity in Plasmodium.