CONTROL OF GENE-EXPRESSION IN TRYPANOSOMES

Trypanosomes are protozoan agents of major parasitic diseases such as Chagas' disease in South America and sleeping sickness of humans and n agana disease of cattle in Africa. They ale transmitted to mammalian h osts by specific insect vectors. Their life cycle consists of a succes sion of differentiation and growth phases requiring regulated gene exp ression to adapt to the changing extracellular environment. Typical of such stage-specific expression is that of the major surface antigens of Trypanosoma brucei, procyclin in the procyclic (insect) form and th e variant surface glycoprotein (VSG) in the bloodstream (mammalian) fo rm. In trypanosomes, the regulation of gene expression is effected mai nly at posttranscriptional levels, since primary transcription of most of the genes occurs in long polycistronic units and is constitutive. The transcripts ale processed by transsplicing and polyadenylation und er the influence of intergenic polypyrimidine tracts. These events sho w some developmental regulation. Untranslated sequences of the mRNAs s eem to play a pi-eminent role in the stage-specific control of individ ual gene expression, through a modulation of mRNA abundance. The VSG a nd procyclin transcription units exhibit particular features that are probably related to the need for a high level of expression. The promo ters and RNA polymerase driving the expression of these units resemble those of the ribosomal genes. Their mutually exclusive expression is ensured by controls operating at several levels, including RNA elongat ion. Antigenic variation in the bloodstream is achieved through DNA re arrangements ol alter-native activation of the telomeric VSG gene expr ession sites. Recent discoveries, such as the existence of a novel nuc leotide in telomeric DNA and the generation of point mutations in VSG genes, have shed new light on the mechanisms and consequences of antig enic variation.