Analysis of a Repeat-Containing Family of Giardia lamblia Variant-Specific Surface Protein Genes: Diversity Through Gene Duplication and Divergence

ABSTRACT. Giardia lamblia trophozoites express on their surfaces one of a set of cysteine-rich antigenically variant proteins, called variant-specific surface proteins, which comprise the majority of proteins detected by surface labeling. While these VSP proteins may be immunodominant proteins important in the host immune response to G. lamblia , the ability to switch expression from one VSP to another may provide a means for the trophozoites to avoid the host immune response. The first VSP characterized, VSPA6 (from the A6 clone of the WB isolate, originally termed CRP170), contains 18–23 copies of a 65 amino acid repeat. We have now used the repeat as a probe to isolate from a WBA6 genomic library two genes related to vspA6 (called vspA6-S1, vspA6-S2). Sequence analysis of the vspA6-S1 gene revealed nearly two complete copies of the 195 bp repeat and substantial nucleotide and translated amino acid similarity in the coding regions 5'and 3'to the repeats. The vspA6-S2 gene, while still related, showed greater divergence from vspA6 than vspA6-S1 in the nonrepeat coding region and contained nearly four copies of a 201 bp repeat that was 75% identical to the 195 bp vspA6 repeat. These results suggest that gene duplication followed by divergence has played a key role in the generation of the vsp gene repertoire.