A TRYPANOSOME METACYCLIC VSG GENE PROMOTER WITH 2 FUNCTIONALLY DISTINCT, LIFE-CYCLE STAGE-SPECIFIC ACTIVITIES

In the mammalian bloodstream, African trypanosomes express the variant surface glycoprotein (VSG), continual switching of which allows evasi on of the host immune response. Bloodstream VSG genes are transcribed from polycistronic bloodstream expression sites with promoters which a re located 45-60 kb upstream. These promoters are not exclusively stag e-regulated, being active in the insect midgut stage where VSG is not expressed. However, the metacyclic VSG (M-VSG) genes, a small subset a ctivated when VSG synthesis begins in the metacyclic stage in the tset se fly salivary glands, are transcriptionally activated specifically i n that stage from promoters <3 kb upstream. Using deletion mapping and transient transfection, we show that the entire 1.22 M-VSC; gene prom oter region (171 bp) is required for full activity in metacyclic-deriv ed trypanosomes. However, a subsidiary, bloodstream stage-specific act ivity is present in its 5' half which directs transcription initiation very close to the initiation site used in metacyclic-derived trypanos omes. Our results imply that the M-VSG gene promoter is longer and mor e complex than other VSG gene promoters.