Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes

Abstract

The expression of genes coding for variable surface glycoproteins (VSGs) in Trypanosoma equiperdum is linked to duplicative transpositions of silent, basic copy sequences into telomere-linked expression sites. Examination of three independently derived late-appearing trypanosome clones expressing VSG-78 revealed that the expressed gene in all cases is composed of sequences derived from three or four individual silent genes. The 182 base pairs at the 3' end of the coding sequence are derived from one silent gene, the 3' donor. The remaining 5' segment is a mosaic structure containing variable-length segments derived from two, or perhaps three, related silent genes. All of the silent genes that participate in the construction of the VSG-78 expression-linked copy (ELC) genes contain multiple stop codons and are unable to code for VSGs. Individual silent pseudogenes complement one another in the mosaic structure of the 5' portions of the ELC genes and create functional VSG genes. The joining of the 3' and 5' portions of the composite genes occurs in short regions of homology and suggests a mechanism by which the ordered expression of the VSG genes is generated.