Variant surface glycoprotein gene expression site switches in Trypanosoma brucei

In Trypanosoma brucei bloodstream forms, transcription of variant surface glycoprotein (VSG) genes occurs at only one of several possible expression sites at any given time. Activation and inactivation of some expression sites are correlated with recombinational events that alter their chromosomal position (Van der Ploeg, L. H. T., Cornelissen, A. W. C. A., Michels, P. A. M., and Borst, P. (1984) Cell 39, 213-221). We present evidence that a 430-kilobase pair (kb) chromosome, containing the 1.8 expression-linked copy, is taken up in a reciprocal recombination when the 1.8 gene is inactivated. As a result, the 430-kb chromosome is reduced in length either to 140 kb (in variant 118b') or to 350 kb (in variant MITat 1.2000) and the 1.8 expression-linked copy is moved to a larger chromosome in both cases. The subsequent activation of the telomeric 118 VSG gene in variant 118b', located on a 2000-kb chromosome, occurs without detectable recombinations while, for variant MITat 1.2000, still another expression site is activated. We discuss a model that explains the occurrence of these apparently random recombinational events at expression site switching and antigenic variation.