Selective telomere activation and the control of antigen gene expression in trypanosomes.

African trypanosomes escape the immune defence of their mammalian host by changing their antigenic surface coat. Antigenic variation occurs through differential gene activation: only one antigen gene is transcribed at a time, among a large collection of specific sequences. This transcription always takes place in a telomere, but it seems that different telomeres can be used alternatively as the gene expression site. Since the trypanosome genome is made up of numerous chromosomes, it would appear that a highly selective process allows the activation of only one telomere at a time. This process seems linked to the differential inactivation of a peculiar telomeric DNA modification system. Two mechanisms allow antigen genes to be expressed. First, a gene copy can be inserted in the expression site by replacing the formerly expressed gene. This is due to gene conversion, whose extent can vary considerably, according to the degree of homology between the recombining partners. The second mechanism involves the activation of another telomere along with deactivation of the telomere containing the previously expressed gene. This form of activation can occur without apparent DNA rearrangement. The alternate use of these mechanisms leads to rapid changes in the antigen gene repertoire, due to gain and loss of different sequences, and to alteration of their activation rate.