Recombination and Diversification of the Variant Antigen Encoding Genes in the Malaria Parasite Plasmodium falciparum.

Overview

The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. These parasites invade and replicate within the circulating red blood cells of infected individuals leading to numerous disease manifestations, including severe anemia, altered circulation, and tissue inflammation. Malaria parasites are also known for their ability to maintain a chronic infection through antigenic variation, the ability to systematically alter the antigens displayed on the surface of infected cells and thereby avoid clearance by the host's antibody response. The genome of P. falciparum includes several large, multicopy gene families that encode highly variable forms of the surface proteins that are the targets of host immunity. Alterations in expression of genes within these families are responsible for antigenic variation. This process requires the continuous generation of new antigenic variants within these gene families, and studies have shown that new variants arise through extensive recombination and gene conversion events between family members. Malaria parasites possess an unusual complement of DNA repair pathways, thus the study of recombination between variant antigen encoding genes provides a unique view into the evolution of mobile DNA in an organism distantly related to the more closely studied model eukaryotes.