Point mutations during generation of expression-linked extra copy of trypanosome surface glycoprotein gene.
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abstract
Trypanosomes exhibit antigenic variation by the sequential expression of a series of antigenically distinct variable surface glycoproteins (VSGs). On the basis of cDNA sequencing and/or terminal amino acid analyses of 10 Trypanosoma brucei VSGs1-6, the approximately 500 amino acids of a nascent VSG can be divided into (N-terminus to C-terminus) a hydrophobic signal peptide (20 amino acids), a variable region (360 amino acids), a homology region (100 amino acids) which can be used to classify the VSGs into one of two homology subsets and a hydrophobic tail (20 amino acids) that is not present in the mature VSG4,5. Expression of some VSGs is accompanied by the production of an expression-linked extra copy (ELC) of a basic copy (BC) VSG gene7-9. We have now compared the sequence of a cDNA representing an ELC gene with its corresponding BC gene sequence. We find that the codons specifying the variable region contain nucleotide changes at 4% of the positions, while those specifying the homology region of the VSG are identical and the 17 codons specifying the C-terminal hydrophobic tail contain 11 nucleotide changes. The 3-nontranslated region between the termination codon and the poly(A) (in the cDNA) is quite different in the two sequences. As the trypanosome serodeme contains only one BC gene coding for this VSG, point mutations seem to be actively introduced into specific areas of the coding sequence during the generation of the ELC gene. These point changes potentially increase the repertoire of immunologically distinct VSGs available to the trypanosome, similar to the way in which somatic mutations contribute to the diversity of the variable regions of immunoglobulins10. An alternative interpretation that cannot be completely eliminated is that a second BC gene is lost during the generation of the ELC. 1982 Nature Publishing Group.
