Characterization of genes coding for two major metacyclic surface antigens in Trypanosoma brucei

In African trypanosomes, only a very small fraction of the total repertoire of variable antigen types (VATs) is expressed by the metacyclic form. In Trypanosoma brucei stock EATRO 1125, the VATs AnTat 1.30 and 1.45 are reproducibly present in about 15% and 4% of the metacyclic population, respectively. The genes encoding the corresponding antigens or variant surface glycoproteins (VSGs) are in telomeres of large chromosomes, as are some non-metacyclic VSG genes from the same stock. Their activation mechanism has been studied in seven independent clones, 3 of which, referred to as 'first wave' metacyclic VATs (M-VATs), have been cloned from the first wave of parasitemia after cyclic transmission. In all these clones, activation of the antigen gene was linked to the transposition of an expression linked copy (ELC) of the gene to a telomeric expression site. For first wave M-VATs, this site seems variable, although restricted to large chromosomes, and it can be re-used for VSG gene expression in the bloodstream form. In 'late bloodstream' M-VATs, isolated from established chronic infections, the active expression site, at the end of a 200 kb chromosome, is the one preferred for the expression of late antigen types. It can be concluded that no characteristic feature in the genomic location and expression mechanism can distinguish metacyclic antigen genes from those expressed in the bloodstream forms, although the control of their expression must clearly be different.