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Research Papers

Antigenic diversity by the recombination of pseudogenes.

Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.

Abstract

During the course of an infection, the hemoflagellate Trypanosoma equiperdum sequentially expresses an extensive repertoire of surface glycoproteins. There is evidence that combinations of silent genes are involved in the generation of this repertoire, but the combination rules are not known. To gain insight into these rules, we determined the fine structure of a composite gene. The gene coding for the variant surface glycoprotein 20 of T. equiperdum is a late gene generated by the partial duplication of three silent pseudogenes. Two closely related but not identical '5' donors' form a mosaic coding for the antigenic portion of the protein. A telomeric '3' donor' provides the last 200 nucleotides of the expressed gene. The sequences of the 5' and 3' donors are not related except for a short segment in which the hybrid junction is formed. These results demonstrate that recombinational processes generate diversity by reassorting sequences and also allow the expression of pseudogenes. Furthermore, the use of a short sequence similarity for the formation of the 5'-3' donor hybrid suggests a mechanism that may act in ordering the expression of the variant surface glycoproteins.

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