Figure 2. Mechanisms of VSG Switching during Antigenic Variation in T. brucei.

The VSG gene expressed prior to a switch (indicated by a blue box) is transcribed from an expression site (ES) that is found at the telomere (vertical black line) of a chromosome (horizontal black line); active transcription of the ES is indicated by a dotted arrow, ESAGs are depicted by black boxes, and 70-bp repeat sequence is shown as a hatched box. Gene conversion to generate a VSG switch can occur by copying a silent VSG (red box) from a subtelomeric array into the ES, replacing the resident VSG; the amount of sequence copied during gene conversion is illustrated, and normally encompasses the VSG ORF and extends upstream to the 70-bp repeats. The silent VSG donor can also be telomeric (either in a mini chromosome or in an inactive ES); here, the downstream limit of conversion can extend to the telomere repeats, while the upstream limit can either be in the 70-bp repeats or the ESAGs (if the donor is in an ES). Segmental VSG conversion involves the copying of sequence from multiple, normally nonfunctional VSGs (pink, red, or green boxes) to generate a novel mosaic VSG in the ES. In transcriptional VSG switching, recombination appears not to be involved; instead, limited transcription at a silent VSG ES (indicated by a small arrow) becomes activated to generate fully active transcription, while the previously active ES is silenced.