Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific

Abstract

Background: In a mammalian host, the cell surface of African trypanosomes is protected by a monolayer of a single variant surface glycoprotein (VSG). The VSG is central to antigenic variation; one VSG gene is expressed at any one time and there is a low frequency stochastic switch to expression of a different VSG gene. The genome of Trypanosoma brucei contains a repertoire of > 1000 VSG sequences. The degree of conservation of the genomic VSG repertoire in different strains has not been investigated in detail.

Results: Eighteen expressed VSGs from Ugandan isolates were compared with homologues (> 40 % sequence identity) in the two available T. brucei genome sequences. Fourteen homologues were present in the genome of Trypanosoma brucei brucei TREU927 from Kenya and fourteen in the genome of T. b. gambiense Dal972 from Cote d'Ivoire. The Ugandan VSGs averaged 71% and 73 % identity to homologues in T. b. brucei and T. b. gambiense respectively. The sequence divergence between homologous VSGs from the three different strains was not random but was more prevalent in the parts of the VSG believed to interact with the host immune system on the living trypanosome.

Conclusion: It is probable that the VSG repertoires in the different isolates contain many common VSG genes. The location of divergence between VSGs is consistent with selection for strain-specific VSG repertoires, possibly to allow superinfection of an animal by a second strain. A consequence of strain-specific VSG repertoires is that any vaccine based on large numbers of VSGs from a single strain will only provide partial protection against other strains.

Figure 1

Location of sequence divergence and solvent accessibility in the primary and tertiary structure of VSG type A N-terminal domains. (a) The tertiary structure of a VSG N-terminal domain dimer with the tertiary structure features coloured in one monomer. The N-terminus is in yellow, the descending alpha helix of the long coiled coil is purple and the ascending helix blue; the surface loops at the top of the VSG are in green. (b) The colours are then used to highlight the same regions in the primary structure in plots of sequence variation (top) between VSG Buteba 4 and homologues from T. b. brucei and T. b. gambiense and below is shown the calculated solvent accessibility for the structurally related VSG MITat1.2.

Figure 2

The location of sequence divergence five sets of three VSG type B in N-terminal domains. The descending alpha helix of the long coiled coil is purple and the ascending helix blue; the surface loops at the top of the VSG are in green. The colours are then used to highlight the same regions in the primary structure in plots of sequence variation. The average variation at each residue for the three different structural components of the VSG is shown below the primary structure representation.