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Draft genome sequencing of Giardia intestinalis assemblage B isolate GS: is human giardiasis caused by two different species?
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2009 (English)In: PLoS Pathogens, ISSN 1553-7366, Vol. 5, no 8, e1000560- p.Article in journal (Refereed) Published
Abstract [en]

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 x 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.

Place, publisher, year, edition, pages
2009. Vol. 5, no 8, e1000560- p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-127462DOI: 10.1371/journal.ppat.1000560ISI: 000270804500015PubMedID: 19696920OAI: oai:DiVA.org:uu-127462DiVA: diva2:330173
Available from: 2010-07-15 Created: 2010-07-13 Last updated: 2013-02-11Bibliographically approved
In thesis
1. Hidden Diversity Revealed: Genomic, Transcriptomic and Functional Studies of Diplomonads
Open this publication in new window or tab >>Hidden Diversity Revealed: Genomic, Transcriptomic and Functional Studies of Diplomonads
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The diplomonads are a diverse group of eukaryotic microbes found in oxygen limited environments such as the intestine of animals were they may cause severe disease. Among them, the prominent human parasite Giardia intestinalis non-invasively colonizes the small intestine of humans and animals where it induces the gastrointestinal disease giardiasis. Two of the eight genetic groups of G. intestinalis, assemblage A and B, are known to infect humans and have zoonotic potential. At the start of project, genome scale data from assemblage B-H was either sparse or entirely missing.

In this thesis, genome sequencing was performed on the assemblage B isolate GS (Paper I) and the P15 isolate (Paper III) of the hoofed-animals specific assemblage E to investigate the underlying components of phenotypic diversity in Giardia. Comparisons to assemblage A isolate WB revealed large genomic differences; entirely different repertoires of surface antigens, genome rearrangements and isolate specific coding sequences of potential bacterial origin. We established that genomic differences are also manifested at the transcriptome level (Paper VIII). In a follow up analysis (Paper IV) we concluded that the Giardia assemblages are largely reproductively isolated. The large genomic differences observed between Giardia isolates can explain the phenotypic diversity of giardiasis.

The adaptation of diplomonads was further studied in Spironucleus barkhanus (Paper II), a fish commensal of grayling, that is closely related to the fish pathogen Spironucleus salmonicida, causative agent of systemic spironucleosis in salmonid fish. We identified substantial genomic differences in the form of divergent genome size, primary sequence divergence and evidence of allelic sequence heterozygosity, a feature not seen in S. salmonicida.

We devised a transfection system for S. salmonicida (Paper VI) and applied it to the study of the mitochondrial remnant organelle (Paper VII). Our analyses showed that S. salmonicida harbor a hydrogenosome, an organelle with more metabolic capabilities than the mitosome of Giardia. Phylogenetic reconstructions of key hydrogenosomal enzymes showed an ancient origin, indicating a common origin to the hydrogenosome in parabasilids and diplomonads.

In conclusion, the thesis has provided important insights into the adaptation of diplomonads in the present and the distant past, revealing hidden diversity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 104 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 990
Giardia intestinalis, Spironucleus salmonicida, Spironucleus barkhanus, intestinal parasite, hydrogenosome, mitosome, lateral gene transfer, horizontal gene transfer, diplomonad, metamonad, sexual recombination, transfection, protein complex purification
National Category
Microbiology Evolutionary Biology Infectious Medicine
Research subject
Biology with specialization in Evolutionary Organismal Biology; Biology with specialization in Microbiology; Biology with specialization in Molecular Biology; Biology with specialization in Molecular Evolution
urn:nbn:se:uu:diva-182831 (URN)978-91-554-8520-7 (ISBN)
Public defence
2012-12-14, B22, Biomedicinskt centrum (BMC), Husargatan 3, Uppsala, 09:00 (English)
Available from: 2012-11-22 Created: 2012-10-16 Last updated: 2013-02-11Bibliographically approved

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Andersson, Jan O.
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