The Giardia lamblia vsp gene repertoire: characteristics, genomic organization, and evolution

Rodney D Adam,Craig A Martens,Hilary G Morrison,Anuranjini Nigam,Stephen F Porcella,Theodore E Nash,Vishwas Seshadri,Rima Patel,Gregory A Farneth

doi:10.1186/1471-2164-11-424

Abstract

BackgroundGiardia lamblia trophozoites colonize the intestines of susceptible mammals and cause diarrhea, which can be prolonged despite an intestinal immune response. The variable expression of the variant-specific surface protein (VSP) genes may contribute to this prolonged infection. Only one is expressed at a time, and switching expression from one gene to another occurs by an epigenetic mechanism.ResultsThe WB Giardia isolate has been sequenced at 10× coverage and assembled into 306 contigs as large as 870 kb in size. We have used this assembly to evaluate the genomic organization and evolution of the vsp repertoire. We have identified 228 complete and 75 partial vsp gene sequences for an estimated repertoire of 270 to 303, making up about 4% of the genome. The vsp gene diversity includes 30 genes containing tandem repeats, and 14 vsp pairs of identical genes present in either head to head or tail to tail configurations (designated as inverted pairs), where the two genes are separated by 2 to 4 kb of non-coding DNA. Interestingly, over half the total vsp repertoire is present in the form of linear gene arrays that can contain up to 10 vsp gene members. Lastly, evidence for recombination within and across minor clades of vsp genes is provided.ConclusionsThe data we present here is the first comprehensive analysis of the vsp gene family from the Genotype A1 WB isolate with an emphasis on vsp characterization, function, evolution and contributions to pathogenesis of this important pathogen.

Highlights

Giardia lamblia trophozoites colonize the intestines of susceptible mammals and cause diarrhea, which can be prolonged despite an intestinal immune response
The vsp genes differ from these other genes encoding cysteine-rich proteins by their possession of a highly conserved 3' end that concludes with the translated amino sequence, CRGKA
We identified a total of 303 vsp genes in the current WB assembly, of which 228 were complete and 75 were in partial or incomplete ORF format

Summary

Introduction

Giardia lamblia trophozoites colonize the intestines of susceptible mammals and cause diarrhea, which can be prolonged despite an intestinal immune response. The variable expression of the variant-specific surface protein (VSP) genes may contribute to this prolonged infection. Humans and other susceptible mammals become infected when cysts are ingested from contaminated water or food and excyst into trophozoites in the proximal small intestine. These trophozoites replicate and cause the symptoms of diarrhea. Infections with Giardia are frequently prolonged and malabsorption with weight loss may last for months in the absence of treatment, despite an immune response that would be expected to eradicate the infection.

Methods

Results

Conclusion