Expression of variant-specific antigen genes in African trypanosomes

Among the large collection of antigen genes present in the Trypanosoma brucei genome, only one is usually transcribed at a time when the parasites develop in the mammalian bloodstream. The antigen gene is transcribed in a telomeric expression site, together with other genes whose function is unknown. The nature of the RNA polymerase and transcription promoter, as well as the overall organization of the transcription unit, suggests that transcription of the antigen gene is of the ribosomal type. This transcription rapidly stops when the temperature of the parasite medium is lowered, probably accounting for the gene inactivation in the procyclic form of the insect midgut. Antigen gene expression resumes in 2 steps: first, induction of specific metacyclic variants occurs in the fly salivary glands, then injection into the blood reactivates the expression site silenced at the procyclic stage. Several telomeres can act as alternative expression sites, but the mechanism for expression-site switching is unknown. In a given expression site, the specificity of the antigen gene can change following gene conversion, telomeric reciprocal recombination, or point mutation. The alternate use of these mechanisms leads to the successive appearance of a very high number of antigenic variants, as well as to rapid evolution of the antigen gene repertoire. The relative extent of homology between nontelomeric antigen genes and the expression site may condition the programming of antigenic variation late in chronic infection, as well as the generation of chimaeric antigen genes.