Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16× coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species.
Giardia intestinalis is a major contributor to the enormous burden of diarrheal diseases with 250 million symptomatic infections per year, and it is part of the WHO neglected disease initiative. Nonetheless, there is poor insight into how Giardia causes disease; it is not invasive, secretes no known toxin and both the duration and symptoms of giardiasis are highly variable. Currently, there are seven defined variants (assemblages) of G. intestinalis, with only assemblages A and B being known to infect humans. Although assemblage B is the most prevalent worldwide, it is inconclusive whether the various genotypes are associated with different disease outcomes. We have used the 454 sequencing technology to sequence the first assemblage B isolate, and the genome was compared to the earlier sequenced assemblage A isolate. Large genetic differences were detected in genes involved in survival of the parasite during infections. The genomic differences between assemblage A and B can explain some of the observed biological and clinical differences between the two assemblages. Our data suggest that assemblage A and B Giardia can be two different species. The identification of genomic differences between assemblages is indeed very important for further studies of the disease and in the development of new methods for diagnosis and treatment of giardiasis.