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Comparative Genomics in Diplomonads: Lifestyle Variations Revealed at Genetic Level
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

As sequencing technologies advance genome studies are becoming a basic tool for studying an organism, and with more genomes available comparative genomics is maturing into a powerful tool for biological research. This thesis demonstrates the strength of a comparative genomics approach on a group of understudied eukaryotes, the diplomonads.

Diplomonads are a group of single cell eukaryotic flagellates living in oxygen-poor environments. Most diplomonads are intestinal parasites, like the well-studied human parasite Giardia intestinalis. There are seven different G. intestinalis assemblages (genotypes) affecting different hosts, and it’s under debate whether these are one species. A genome-wide study of three G. intestinalis genomes from different assemblages reveals little inter-assemblage sexual recombination, supporting that the different G. intestinalis assemblages are genetically isolated and thus different species.

A genomic comparison between the fish parasite S. salmonicida and G. intestinalis reveals genetic differences reflecting differences in their parasitic lifestyles. There is a tighter transcriptional regulation and a larger metabolic reservoir in S. salmonicida, likely adaptations to the fluctuating environments it encounters during its systemic infection compared to G. intestinalis which is a strict intestinal parasite.

The S. salmonicida genome analysis also discovers genes involved in energy metabolism. Some of these are experimentally shown to localize to mitochondrion-related organelles in S. salmonicida, indicating that they possess energy-producing organelles that should be classified as hydrogenosomes, as opposed to the mitosomes in G. intestinalis.

A transcriptome analysis of the free-living Trepomonas is compared with genomic data from the two parasitic diplomonads. The majority of the genes associated with a free-living lifestyle, like phagocytosis and a larger metabolic capacity, are of prokaryotic origin. This suggests that the ancestor of the free-living diplomonad was likely host-associated and that the free-living lifestyle is a secondary adaptation acquired through horizontal gene transfers. 

In conclusion, this thesis uses different comparative genomics approaches to broaden the knowledge on diplomonad diversity and to provide more insight into how the lifestyle differences are reflected on the genetic level. The bioinformatics pipelines and expertise gained in these studies will be useful in other projects in diplomonads and other organismal groups.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. , 64 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1261
Keyword [en]
comparative genomics, Giardia intestinalis, Spironucleus salmonicida, Trepomonas, diplomonad, intestinal parasite, free-living, sexual recombination, hydrogenosome, horizontal gene transfer
National Category
Bioinformatics and Systems Biology Evolutionary Biology Microbiology
Research subject
Biology with specialization in Molecular Evolution
URN: urn:nbn:se:uu:diva-251650ISBN: 978-91-554-9262-5OAI: oai:DiVA.org:uu-251650DiVA: diva2:807221
Public defence
2015-06-12, BMC, B41, Husargatan 3, Uppsala, 13:00 (English)
Available from: 2015-05-22 Created: 2015-04-23 Last updated: 2015-07-07Bibliographically approved
List of papers
1. Genome-Wide Analyses of Recombination Suggest That Giardia intestinalis Assemblages Represent Different Species
Open this publication in new window or tab >>Genome-Wide Analyses of Recombination Suggest That Giardia intestinalis Assemblages Represent Different Species
2012 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 29, no 10, 2895-2898 p.Article in journal (Refereed) Published
Abstract [en]

Giardia intestinalis is a major cause of waterborne enteric disease in humans. The species is divided into eight assemblages suggested to represent separate Giardia species based on host specificities and the genetic divergence of marker genes. We have investigated whether genome-wide recombination occurs between assemblages using the three available G. intestinalis genomes. First, the relative nonsynonymous substitution rates of the homologs were compared for 4,009 positional homologs. The vast majority of these comparisons indicate genetic isolation without interassemblage recombinations. Only a region of 6 kbp suggests genetic exchange between assemblages A and E, followed by gene conversion events. Second, recombination-detecting software fails to identify within-gene recombination between the different assemblages for most of the homologs. Our results indicate very low frequency of recombination between the syntenic core genes, suggesting that G. intestinalis assemblages are genetically isolated lineages and thus should be viewed as separated Giardia species.

National Category
Natural Sciences Medical and Health Sciences
urn:nbn:se:uu:diva-175947 (URN)10.1093/molbev/mss107 (DOI)000309927900003 ()22474166 (PubMedID)
Available from: 2012-06-14 Created: 2012-06-14 Last updated: 2015-07-07Bibliographically approved
2. Hydrogenosomes in the diplomonad Spironucleus salmonicida
Open this publication in new window or tab >>Hydrogenosomes in the diplomonad Spironucleus salmonicida
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2013 (English)In: Nature Communications, ISSN 2041-1723, Vol. 4, 2493- p.Article in journal (Refereed) Published
Abstract [en]

Acquisition of the mitochondrion is a key event in the evolution of the eukaryotic cell, but diversification of the organelle has occurred during eukaryotic evolution. One example of such mitochondria-related organelles (MROs) are hydrogenosomes, which produce ATP by substrate- level phosphorylation with hydrogen as a byproduct. The diplomonad parasite Giardia intestinalis harbours mitosomes, another type of MRO. Here we identify MROs in the salmon parasite Spironucleus salmonicida with similar protein import and Fe-S cluster assembly machineries as in Giardia mitosomes. We find that hydrogen production is prevalent in the diplomonad genus Spironucleus, and that S. salmonicida MROs contain enzymes characteristic of hydrogenosomes. Evolutionary analyses of known hydrogenosomal components indicate their presence in the diplomonad ancestor, and subsequent loss in Giardia. Our results suggest that hydrogenosomes are metabolic adaptations predating the split between parabasalids and diplomonads, which is deeper than the split between animals and fungi in the eukaryotic tree.

National Category
Natural Sciences
urn:nbn:se:uu:diva-210741 (URN)10.1038/ncomms3493 (DOI)000325534300002 ()
Available from: 2013-11-14 Created: 2013-11-14 Last updated: 2015-11-13Bibliographically approved
3. The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments
Open this publication in new window or tab >>The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments
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2014 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 2, e1004053- p.Article in journal (Refereed) Published
Abstract [en]

Spironucleus salmonicida causes systemic infections in salmonid fish. It belongs to the group diplomonads, binucleated heterotrophic flagellates adapted to micro-aerobic environments. Recently we identified energy-producing hydrogenosomes in S. salmonicida. Here we present a genome analysis of the fish parasite with a focus on the comparison to the more studied diplomonad Giardia intestinalis. We annotated 8067 protein coding genes in the ∼12.9 Mbp S. salmonicida genome. Unlike G. intestinalis, promoter-like motifs were found upstream of genes which are correlated with gene expression, suggesting a more elaborate transcriptional regulation. S. salmonicida can utilise more carbohydrates as energy sources, has an extended amino acid and sulfur metabolism, and more enzymes involved in scavenging of reactive oxygen species compared to G. intestinalis. Both genomes have large families of cysteine-rich membrane proteins. A cluster analysis indicated large divergence of these families in the two diplomonads. Nevertheless, one of S. salmonicida cysteine-rich proteins was localised to the plasma membrane similar to G. intestinalis variant-surface proteins. We identified S. salmonicida homologs to cyst wall proteins and showed that one of these is functional when expressed in Giardia. This suggests that the fish parasite is transmitted as a cyst between hosts. The extended metabolic repertoire and more extensive gene regulation compared to G. intestinalis suggest that the fish parasite is more adapted to cope with environmental fluctuations. Our genome analyses indicate that S. salmonicida is a well-adapted pathogen that can colonize different sites in the host.

National Category
Microbiology Genetics
urn:nbn:se:uu:diva-224545 (URN)10.1371/journal.pgen.1004053 (DOI)000332021500041 ()24516394 (PubMedID)
Available from: 2014-05-14 Created: 2014-05-14 Last updated: 2015-07-07Bibliographically approved
4. On the reversibility of parasitism: adaptation to a free-living lifestyle via gene acquisitions in the diplomonad Trepomonas sp PC1
Open this publication in new window or tab >>On the reversibility of parasitism: adaptation to a free-living lifestyle via gene acquisitions in the diplomonad Trepomonas sp PC1
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2016 (English)In: BMC Biology, ISSN 1741-7007, E-ISSN 1741-7007, Vol. 14, 62Article in journal (Refereed) Published
Abstract [en]

Background: It is generally thought that the evolutionary transition to parasitism is irreversible because it is associated with the loss of functions needed for a free-living lifestyle. Nevertheless, free-living taxa are sometimes nested within parasite clades in phylogenetic trees, which could indicate that they are secondarily free-living. Herein, we test this hypothesis by studying the genomic basis for evolutionary transitions between lifestyles in diplomonads, a group of anaerobic eukaryotes. Most described diplomonads are intestinal parasites or commensals of various animals, but there are also free-living diplomonads found in oxygen-poor environments such as marine and freshwater sediments. All these nest well within groups of parasitic diplomonads in phylogenetic trees, suggesting that they could be secondarily free-living. Results: We present a transcriptome study of Trepomonas sp. PC1, a diplomonad isolated from marine sediment. Analysis of the metabolic genes revealed a number of proteins involved in degradation of the bacterial membrane and cell wall, as well as an extended set of enzymes involved in carbohydrate degradation and nucleotide metabolism. Phylogenetic analyses showed that most of the differences in metabolic capacity between free-living Trepomonas and the parasitic diplomonads are due to recent acquisitions of bacterial genes via gene transfer. Interestingly, one of the acquired genes encodes a ribonucleotide reductase, which frees Trepomonas from the need to scavenge deoxyribonucleosides. The transcriptome included a gene encoding squalene-tetrahymanol cyclase. This enzyme synthesizes the sterol substitute tetrahymanol in the absence of oxygen, potentially allowing Trepomonas to thrive under anaerobic conditions as a free-living bacterivore, without depending on sterols from other eukaryotes. Conclusions: Our findings are consistent with the phylogenetic evidence that the last common ancestor of diplomonads was dependent on a host and that Trepomonas has adapted secondarily to a free-living lifestyle. We believe that similar studies of other groups where free-living taxa are nested within parasites could reveal more examples of secondarily free-living eukaryotes.

Free-living; Parasite; Diplomonad; Dollo's law; Reversibility; Trepomonas; Horizontal gene transfer; Ribonucleotide reductase
National Category
Evolutionary Biology
urn:nbn:se:uu:diva-251638 (URN)10.1186/s12915-016-0284-z (DOI)000381184600002 ()27480115 (PubMedID)
Swedish Research Council Formas, 2010-899Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Research Council

Correction in: BMC Biology, vol. 14, article number 77

DOI: 10.1186/s12915-016-0302-1

Available from: 2015-04-23 Created: 2015-04-22 Last updated: 2016-10-07Bibliographically approved

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