Preferential activation of telomeric variant surface glycoprotein genes in Trypanosoma brucei

Abstract

During an infection, Trypanosoma brucei expresses diverse variant surface glycoprotein (VSG) genes in a quasi-sequential order. Numerous VSG genes have intrachromosomal locations but many are located adjacent to telomeres. We have tested whether telomeric VSG genes are preferentially activated compared to intrachromosomal VSG genes during an antigenic switch. The frequency with which the IsTat II VSG gene is expressed in first relapse populations has been compared for variant antigenic types (VATs) A 3 and A 11. These VATs express the same A VSG gene from the same chromosome but VAT A 11 contains an inactive telomeric 11 VSG gene which is absent in VAT A 3. The 11 gene is activated at a much higher frequency in first relapse populations from VAT A 11 than from VAT A 3. A resultant VAT 11 clone was examined in detail and shown to have reactivated the telomeric 11 VSG gene. These results suggest that a telomeric location can result in a greater frequency of activation of a VSG gene. This preferential activation may explain, in part, the order of expression of VSG genes.