Trypanosome surface antigen (VSG) switching

Content
Regulation of Gene Expression 3. A Variety of Mechanisms in Eukaryotes
Regulation at Transcription Level
Activation of transcription
Britten-Davidson model for unit of transcription
Gene battery
Chromosomal proteins and gene expression
Repression of transcription 
Specific DNA sequences controlling transcription
Transgenic plants to study regulatory sequences
Modification of DNA sequences and their transcripts in gene expression
Alternative splicing of transcripts
Regulation at translation level
Activation and repression of translation
Masked mRNA in eggs of sea urchin and Xenopus
Regulation by gene re-arrangement
Expression of immunoglobulin genes
Yeast mating type switching
Trypanosome surface antigen (VSG) switching
Synthesis of mRNA in pieces in VSG genes in trypanosome
Regulation by reversible phosphorylation
Signal transduction and second messengers
Proteins and peptide hormones and gene expression
Steroid hormones and gene expression
Interferon stimulated gene expression (without a second messenger)
Cell surface receptors in cholesterol metabolism and drug production
Ubiquitin protein and regulation of heat shock genes


Trypanosome surface antigen (VSG) switching
Sleeping sickness in humans (and a related disease in cow) is caused by a unicellular parasite called trypanosome, which alternates between two hosts, tsetse fly and a mammal (Fig. 37.19). Trypanosome undergoes important biochemical changes involving diversity in the variable surface glycoprotein (VSG), a major component of surface coat, which provides antigenic reaction. Although, at any one time a trypanosome expresses only one VSG, its ability to change into any of the ~100 possible different VSGs is the secret of parasite's survival during fly-mammal cycle.

A tsetse fly, during a bite, gains the parasite, which loses its VSG but re-acquires a new VSG after three weeks when, it differentiates in 'metacyclic form'. This form enters mammalian bloodstream during a bite, where VSG keeps on changing every 1-2 weeks, so that the immune response always lags behind the change in VSG and the parasite evades the immune surveillance, perpetuating indefinitely, till it enters the central nervous system and often causes death.
 
Life cycle of a trypanosome alternating between two hosts (tsetse fly and a mammal) causing sleeping sickness.
Fig. 37.19. Life cycle of a trypanosome alternating between two hosts (tsetse fly and a mammal) causing sleeping sickness.

Genes (about 1000) for ~ 100 different VSGs are present scattered on different chromosomes in the genome of trypanosome. Diversity, therefore, depends on changing expression from one pre-existing gene to another. Each VSG is coded by a single basic copy gene, which may be telomeric or internal in location, and there may be several isogenes for same VSG or similar VSGs. The copy of the gene, which is active, is called expression linked copy (ELC) and is located on an expression site. Creation of an ELC may involve transfer of a basic copy gene to the expression site or vice versa. Almost all switches in VSG type involve replacement of the ELC by a pre-existing silent copy.