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Nucleic Acids Research, 1985, Vol. 13, No. 13 4661-4676
© 1985

Articles

Characteristics of trypanosome variant antigen genes active in the tsetse fly

Albert W.C.A. Cornelissen, Guus A.M. Bakkeren, J.David Barry1, Paul A.M. Michels* and Piet Borst

Division of Molecular Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis) Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands 1Institute of Genetics, University of Glasgow Church Street, Glasgow G11 5JS, UK

Received May 10, 1985. Revised May 20, 1985. Accepted June 20, 1985.

Trypanosoma brucei contains a repertoire of more than 100 different genea for Variant Surface Glycoproteins (VSGs). A small and strain-specific fraction of these genes is expressed in the salivary glands of the tsetse fly (M-genes), giving rise to metscyclic Variable Antigen Types (M-VATs). Antibodies produced in a chronic trypanosome infection initiated by syringe inoculation of bloodstream forms into mammals (i.e. against B-VATs) , will react with most of the M-VATs suggesting that these B-VATs express VSG genes that are similar or identical to M-genes. We have cloned DNA complementary to the VSG mRNA of four of such B-VATs and used this to characterize the corresponding VSG genes. In three of the four VATs we find a single VSG gene hybridizing with the cDNA probe and we provide supporting evidence that this gene is expressed as an M-gene. In the bloodstream repertoire these genes appear to be activated by duplicative translocation to another telomere. In all four variants the putative M-genes are telomeric and in the three cases where the location of the genes on chromosome-sized DNA molecules could be determined, the genes were located in large DNA, whereas the majority of the telomeric VSG genes are in chromosomes < 1000 kb. Our results are best explained by models for M-gene activation involving telomeric expression sites for these genes which are separate from those used by bloodstream forms. The implications of these results for vaccination are discussed.

*Present address: International Institute of Cellular and Molecular Pathology, Avenue Hippocrate 74, B-1200 Brussels, Belgium


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