Giardia lamblia: identification and characterization of a variant-specific surface protein gene family

Giardia lamblia trophozoites undergo antigenic variation by modulating the expression of variant-specific surface proteins (VSP), which are encoded by a number of small multigene families. We characterized the genomic copy of the VSP gene expressed by the cloned trophozoite line H7, derived from the isolate GS/M, in addition to a related, but nonexpressed, family member. The coding regions of the two genes encode closely related polypeptides (86% identity). However, differences in the coding region of these genes reside solely in an 873 bp segment. Only four differences were found between the 5' flanking sequences (465 bp). The proximal 205 base pairs downstream from the coding regions were identical, but thereafter the sequences diverged (37% identity over the next 391 bp). Mapping studies indicated that no other VSP gene was located within 4 kb pairs of the expressed H7 VSP gene, and transcripts from the nonexpressed gene were detected in neither GS/H7 nor heterogeneous trophozoites populations derived from this cloned line. Any mechanisms responsible for the differential expression of VSP genes must reconcile the near identity of DNA sequences that flank the coding regions of expressed and nonexpressed VSP genes.