The Contribution of Chromosomal Translocations to Antigenic Variation in Trypanosoma Brucei

Genomic rearrangements influencing gene expression occur throughout nature. Several of these rearrangements disrupt normal gene expression, as exemplified by the genetic alterations caused by the mobile genetic elements of maize or Drosophila (see Shapiro 1983). Other rearrangements are part of the normal developmental programme of an organism. An understanding of the control of genomic rearrangements and their effects on gene expression should contribute to our insight into the mechanism of genetic programming and cellular development. The protozoan parasite Trypanosoma brucei exhibits a variety of genomic rearrangements that influence the expression of genes that code for versions of the variant surface glycoprotein (v.s.g.), which makes up the cell surface coat. V.s.g. genes are expressed in a mutually exclusive manner. Several v.s.g. genes are activated by duplicative transposition of the gene to a telomeric expression site where they are transcribed, while others can be activated without detectable genomic rearrangements. Recently we have been able to fractionate the chromosomes of T. brucei in agarose gels (Van der Ploeg et al. 1984a). This led to the observations that duplicative transpositions occur inter-chromosomally and that the chromosomes of T. brucei are subject to frequent recombinations that displace hundreds of kilobase pairs. At least two and possibly more telomeric expression sites can be used for v.s.g. gene transcription. How these sites are activated and inactivated is still unsolved, but this does not depend on recombinations in the vicinity of the gene. Gross genomic rearrangements occur sometimes in correlation with antigenic switching and this suggests that such rearrangements have a function in regulating the mutually exclusive transcription of the different expression sites. V.s.g. genes consist of two exons. No physical linkage of the 35 nucleotide (n.t.) mini-exon to the v.s.g. gene main exon occurred within 15 kilobase pairs in variant 118a and possibly 150 kilobase pairs in variant 1.8b. These mapping data give additional support for the hypothesis that both exons might represent separate transcription units. Transcription initiation of v.s.g. genes would thus be from a promotor other than the mini-exon repeat unit. We propose that transcription of the v.s.g. gene in the expression site can be regulated by a position effect on the gene.