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Sequence divergence in a family of variant surface glycoprotein genes from trypanosomes: Coding region hypervariability and downstream recombinogenic repeats

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Abstract

The surface of the parasitic protozoanTrypanosoma brucei spp. is covered with a dense coat consisting of a single type of glycoprotein molecule, the variant surface glycoprotein (VSG). There may be as many as 1,000 genes for VSG within the genome ofT. brucei, and the switch of expression from one to another is the phenomenon of antigenic variation. As an approach to understanding the evolution of VSG genes we have determined the genomic DNA sequences of the eight genes encoding the variant surface glycoprotein 117 (VSG) family. From these data we have observed a number of features concerning the relationships between these genes: (1) there is a region of high variability confined to the N-terminus of the coding sequence, and comparison of the sequences with the available X-ray diffraction crystal structures suggests that two of the most variable stretches within the N-terminal domain are present on surface-exposed loops, indicating a role for epitope selection in evolution of these genes; (2) the 29 nucleotides surrounding the splice acceptor site are absolutely conserved in all eight 117 VSG genes; (3) numerous insertion/deletion mutations are located within or immediately downstream of the C-terminal protein-coding sequences: (4) within 500 by downstream of the insertion/deletion mutations are one or two copies of a repeat motif highly homologous to the recombinogenic 76-bp repeat sequences present upstream of many VSG basic copy genes and the expression-linked copy.

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Abbreviations

BC:

basic copy

ELC:

expression-linked copy

ES:

expression site

GPI:

glycosylphosphatidylinositol; indel, mutation where insertion or deletion cannot be discriminated; (k)bp, (kilo)base pairs

ORF:

open reading frame

URS:

upstream repeat sequence (also known as 76-bp repeats)

UTR:

untranslated region

VSG:

variant surface glycoprotein. The nucleotide sequences presented in this paper have been submitted to GeDBank with the following accession numbers; pSUB85, L31608; pSUB70C, L31607; pSUB70A, L31606; pSUB60, L31605; pSUB55, L31604; pSUB52, L31603; pSUB50, L31602 and the 117 basic copy (pGB 117), L34415

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Author notes

  1. Mark C. Field

    Present address: Laboratory of Cell Biology, Department of Biochemistry, Imperial College of Science, Technology and Medicine, SW7 2AY, London, UK

Authors and Affiliations

  1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, 94305, Stanford, CA, USA

    Mark C. Field & John C. Boothroyd

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  1. Mark C. Field
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  2. John C. Boothroyd
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Correspondence to: J.C. Boothroyd

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Field, M.C., Boothroyd, J.C. Sequence divergence in a family of variant surface glycoprotein genes from trypanosomes: Coding region hypervariability and downstream recombinogenic repeats. J Mol Evol 42, 500–511 (1996). https://doi.org/10.1007/BF02352280

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  • DOI: https://doi.org/10.1007/BF02352280

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