Molecular players of homologous recombination in protozoan parasites: implications for generating antigenic variation

A major impediment to vaccine development against infections caused by protozoan parasites such as Plasmodium falciparum and Trypanosoma is the extraordinary ability of these parasites to rapidly change their surface molecules, a phenomenon known as antigenic variation. A prominent determinant of antigenic variation in these organisms is associated with rearrangements of genes, especially those known as var in P. falciparum and vsg in Trypanosoma. However, mechanisms underlying generation of anitgenic diversities among these protozoan parasites are poorly understood. The hypothesis that links all the different sections in this review is that antigenic variations in the protozoan parasites is coupled with genetic rearrangements, which occur during the course of DNA break repair. Here, we provide comprehensive and up-to-date information on Rad51 in these organisms, an eukaryotic homologue of bacterial RecA, and homologous recombination mechanisms. In trypanosomes both Rad51- dependent and -independent mechanisms have been suggested to play roles in antigenic variation. Finally, we speculate on how might similar DNA repair mechanisms contribute to genetic rearrangement associated with antigenic variation in the apicomplexan Plasmodium parasites, an immune evasion strategy. (C) 2004 Elsevier B.V. All rights reserved.