Trypanosoma brucei evades the host
immune response by sequential expression of a large family of variant
surface glycoproteins (VSG) from one of ~20 subtelomeric expression
sites (ES). VSG transcription is monoallelic, and little is
known about the regulation of antigenic switching. To explore whether
telomere length could affect antigenic switching, we created a
telomerase-deficient cell line, in which telomeres shortened at a
rate of 3-6 bp at each cell division. Upon reaching a critical
length, short silent ES telomeres were stabilized by a
telomerase-independent mechanism. The active ES telomere
progressively shortened and frequently broke. Upon reaching a
critical length, the short active ES telomere stabilized, but the
transcribed VSG was gradually lost from the population and
replaced by a new VSG through duplicative gene conversion. We
propose a model in which subtelomeric break induced replication
mediated repair at a short ES telomere leads to duplicative gene
conversion and expression of a new VSG.