Molecular Genetics

Some parasites evade host immune responses by altering their surace antigens by DNA rearrangements.

Facts

Trypanosomes are tsetse fly-transmitted blood parasites. They are successful parasites because they dodge the host's immune response by changing the antigenic component of their surfaces. The surface antigenic properties are due to a single protein, the variant surface glycoprotein (VSG). The active VSG gene (ELC, expression-linked copy) is located near the end of a chromosome. The VSG message is the 5' most part of a 55 to 60 knt transcript. The transcript is processed by trans-splicing to yield mRNAs for several surface proteins.

There are, in addition, about 20 silent VSG genes near telomeres and about 1000 silent VSG genes at other locations. Several mechanisms of antigen shift are suggested by Southern analysis using the active gene to probe DNA before and after the shift. Silencing of an ELC locus is associated with a base modification, a glucosyl hydroxymethyl uracil.

Interpretations

• A telomeric storage locus may be activated to be an ELC, with inactivation of the old ELC.
• An active ELC may have its sequence converted to that of one of the storage loci.
• The replacement of information at an expression locus resembles the switching of information for yeast mating types.

• Trypanosomiasis is a serious disease in the tropics.
• Status of international research on VSG genes was summarized in 1996.
• Bacteria, such as Salmonella typhimurium, also switch surface antigens by DNA rearrangements.
• A variety of mechanisms result in variation of surface antigens of mycoplasma.
• The VSG rearrangement is but one example of programmed rearrangement.

This is page 3244 of Molecular Genetics by Ulrich Melcher, © 1997, 1998, 1999