Stability of expression-linked surface antigen gene in Trypanosoma equiperdum

Abstract

African trypanosomes evade clearance in immune-competent hosts by periodically replacing their major surface glycoprotein with an antigenically different glycoprotein^1–4. Expression of many of these variant surface glycoproteins (VSGs) is associated with the duplication and transposition of silent basic copy genes (BCs) into unlinked genomic expression sites^5–10. The new expression-linked VSG gene copies (ELCs) are oriented with their 3′ ends proximal to chromosome telomeres^11–14. Other VSG genes are activated without the production of an ELC^10,15–18.The 3′ ends of these VSG genes are near chromosome telomeres both when they are active and when they are inactive. Recently, we have shown that activation of the VSG-1 gene in the BoTaR (Bordeaux trypanozoon antigen repertoire) serodeme of Trypanosoma equiperdum involves the duplication and transposition of a telomeric BC gene into one of at least three unlinked telomeric sites⁹. Here we show that the VSG-1 ELC is inactivated but not eliminated in some antigenic variants derived from a VSG-1 expressor. In addition, a subsequent variant that again expresses VSG-1 has not reactivated the residual VSG-1 ELC (R-ELC), but instead contains a new, active VSG-1 ELC in an unlinked telomeric site. These results show that the simple presence of an ELC in a potential expression site is not sufficient for its expression.