Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation

In Trypanosoma brucei, DNA recombination is crucial in antigenic variation, a strategy for evading the mammalian host immune system found in a wide variety of pathogens. T. brucei has the capacity to encode > 1000 antigenically distinct variant surface glycoproteins (VSGs). By ensuring that only one VSG is expressed on the cell surface at one time, and by periodically switching the VSG gene that is expressed, T. brucei can evade immune killing for prolonged periods. Much of VSG switching appears to rely on a widely conserved DNA repair pathway called homologous recombination, driven by RAD51. Here, we demonstrate that T. brucei encodes a further five RAD51-related proteins, more than has been identified in other single-celled eukaryotes to date. We have investigated the roles of two of the RAD51-related proteins in T. brucei, and show that they contribute to DNA repair, homologous recombination and RAD51 function in the cell. Surprisingly, however, only one of the two proteins contributes to VSG switching, suggesting that the family of diverged RAD51 proteins present in T. brucei have assumed specialized functions in homologous recombination, analogous to related proteins in metazoan eukaryotes.