Surface epitope variation via mosaic gene formation is potential key to long-term survival of Trypanosoma brucei.

Trypanosoma brucei evades the immune response of its mammalian host by antigenic variation in the major surface antigen (the variable surface glycoprotein or VSG). We examined the generation of diversity in 4 in vivo-derived antigenically related clones of T. brucei by sequencing VSG cDNA from each of the 4 clones and all 5 related genomic copies in the WaTat 1.1 progenitor organism. Each expressed VSG gene was a different mosaic of basic copy genes; 3 were complex mosaics consisting of multiple fragments from at least 3 basic copy genes. All 4 basic copy genes were involved in mosaic gene formation even though at least 2 were pseudogenes. Point mutations were a minor component to VSG variability. We conclude that, in vivo, expression of mosaic VSG genes amplifies the effective surface antigen repertoire of T brucei. We propose that this additional source of antigenic variation is crucial to long term survival of the parasite in its mammalian host, and may be the primary function of VSG multigene families in trypanosomes.