Point mutations are associated with a gene duplication leading to the bloodstream reexpression of a trypanosome metacyclic VSG

Abstract

African trypanosomes evade the immune response of their hosts by sequentially expressing different variant surface glycoproteins (VSGs). We isolated a bloodstream trypanosome clone of Trypanosoma brucei rhodesiense that expresses a VSG normally present during the metacyclic stage of the parasite in the insect vector. Associated with the bloodstream reexpression of this metacyclic VSG is a gene conversion in which the duplicated, expressed gene of 1650 nt contains 11 scattered point mutations when compared with its donor gene. Analysis of an uncloned population of bloodstream trypanosomes revealed another VSG reexpressor of the same donor gene in which the coding region had undergone 24 point mutations. The mutations are unique to the duplicated gene and appear to be nontemplated. The generation of these mutations provides a way for the trypanosome to increase further its antigenic diversity.