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Stairs, Courtney W.
Publications (9 of 9) Show all publications
Stairs, C. W., Kokla, A., Astvaldsson, A., Jerlström-Hultqvist, J., Svärd, S. & Ettema, T. J. G. (2019). Oxygen induces the expression of invasion and stress response genes in the anaerobic salmon parasite Spironucleus salmonicida. BMC Biology, 17(1), Article ID 19.
Open this publication in new window or tab >>Oxygen induces the expression of invasion and stress response genes in the anaerobic salmon parasite Spironucleus salmonicida
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2019 (English)In: BMC Biology, ISSN 1741-7007, E-ISSN 1741-7007, Vol. 17, no 1, article id 19Article in journal (Refereed) Published
Abstract [en]

Background: Spironucleus salmonicida is an anaerobic parasite that can cause systemic infections in Atlantic salmon. Unlike other diplomonad parasites, such as the human pathogen Giardia intestinalis, Spironucleus species can infiltrate the blood stream of their hosts eventually colonizing organs, skin and gills. How this presumed anaerobe can persist and invade oxygenated tissues, despite having a strictly anaerobic metabolism, remains elusive.

Results: To investigate how S. salmonicida response to oxygen stress, we performed RNAseq transcriptomic analyses of cells grown in the presence of oxygen or antioxidant-free medium. We found that over 20% of the transcriptome is differentially regulated in oxygen (1705 genes) and antioxidant-depleted (2280 genes) conditions. These differentially regulated transcripts encode proteins related to anaerobic metabolism, cysteine and Fe-S cluster biosynthesis, as well as a large number of proteins of unknown function. S. salmonicida does not encode genes involved in the classical elements of oxygen metabolism (e.g., catalases, superoxide dismutase, glutathione biosynthesis, oxidative phosphorylation). Instead, we found that genes encoding bacterial-like oxidoreductases were upregulated in response to oxygen stress. Phylogenetic analysis revealed some of these oxygen-responsive genes (e.g., nadh oxidase, rubrerythrin, superoxide reductase) are rare in eukaryotes and likely derived from lateral gene transfer (LGT) events into diplomonads from prokaryotes. Unexpectedly, we observed that many host evasion- and invasion-related genes were also upregulated under oxidative stress suggesting that oxygen might be an important signal for pathogenesis.

Conclusion: While oxygen is toxic for related organisms, such as G. intestinalis, we find that oxygen is likely a gene induction signal for host invasion- and evasion-related pathways in S. salmonicida. These data provide the first molecular evidence for how S. salmonicida could tolerate oxic host environments and demonstrate how LGT can have a profound impact on the biology of anaerobic parasites.

Keywords
Anaerobiosis, Diplomonads, Giardia, Lateral gene transfer, Oxygen stress, Parasitology, Protist, RNAseq, Spironucleosis, Spironucleus
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-378917 (URN)10.1186/s12915-019-0634-8 (DOI)000459961200001 ()
Funder
EU, European Research Council, 310039-PUZZLE_CELLSwedish Foundation for Strategic Research Swedish Research Council, 2015-04959Swedish Research Council Formas, 2016-00539
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-03-22Bibliographically approved
Spang, A., Stairs, C. W., Dombrowski, N., Eme, L., Lombard, J., Caceres, E. F., . . . Ettema, T. J. G. (2019). Proposal of the reverse flow model for the origin of the eukaryotic cell based on comparative analyses of Asgard archaeal metabolism. Nature Microbiology, 4(7), 1138-1148
Open this publication in new window or tab >>Proposal of the reverse flow model for the origin of the eukaryotic cell based on comparative analyses of Asgard archaeal metabolism
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2019 (English)In: Nature Microbiology, E-ISSN 2058-5276, Vol. 4, no 7, p. 1138-1148Article in journal (Refereed) Published
Abstract [en]

The origin of eukaryotes represents an unresolved puzzle in evolutionary biology. Current research suggests that eukaryotes evolved from a merger between a host of archaeal descent and an alphaproteobacterial endosymbiont. The discovery of the Asgard archaea, a proposed archaeal superphylum that includes Lokiarchaeota, Thorarchaeota, Odinarchaeota and Heimdallarchaeota suggested to comprise the closest archaeal relatives of eukaryotes, has helped to elucidate the identity of the putative archaeal host. Whereas Lokiarchaeota are assumed to employ a hydrogen-dependent metabolism, little is known about the metabolic potential of other members of the Asgard superphylum. We infer the central metabolic pathways of Asgard archaea using comparative genomics and phylogenetics to be able to refine current models for the origin of eukaryotes. Our analyses indicate that Thorarchaeota and Lokiarchaeota encode proteins necessary for carbon fixation via the Wood-Ljungdahl pathway and for obtaining reducing equivalents from organic substrates. By contrast, Heimdallarchaeum LC2 and LC3 genomes encode enzymes potentially enabling the oxidation of organic substrates using nitrate or oxygen as electron acceptors. The gene repertoire of Heimdallarchaeum AB125 and Odinarchaeum indicates that these organisms can ferment organic substrates and conserve energy by coupling ferredoxin reoxidation to respiratory proton reduction. Altogether, our genome analyses suggest that Asgard representatives are primarily organoheterotrophs with variable capacity for hydrogen consumption and production. On this basis, we propose the 'reverse flow model', an updated symbiogenetic model for the origin of eukaryotes that involves electron or hydrogen flow from an organoheterotrophic archaeal host to a bacterial symbiont.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-393531 (URN)10.1038/s41564-019-0406-9 (DOI)000480348200010 ()30936488 (PubMedID)
Funder
EU, European Research Council, 310039-PUZZLE_CELLSwedish Foundation for Strategic Research , SSF-FFL5Swedish Research Council, 2015-04959Swedish Research Council, 2016-03559Australian Research Council, DE170100310Australian Research Council, DP180101762
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Karnkowska, A., Treitli, S. C., Brzon, O., Novak, L., Vacek, V., Soukal, P., . . . Hampl, V. (2019). The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion. Molecular biology and evolution, 36(10), 2292-2312
Open this publication in new window or tab >>The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion
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2019 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 36, no 10, p. 2292-2312Article in journal (Refereed) Published
Abstract [en]

The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less "reduced" than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe-S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2019
Keywords
amitochondrial eukaryote, cell biology, Monocercomonoides, oxymonads, protist genomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-400822 (URN)10.1093/molbev/msz147 (DOI)000501734200017 ()31387118 (PubMedID)
Funder
EU, Horizon 2020, 771592
Available from: 2020-01-13 Created: 2020-01-13 Last updated: 2020-01-13Bibliographically approved
Narrowe, A. B., Spang, A., Stairs, C. W., Caceres, E. F., Baker, B. J., Miller, C. S. & Ettema, T. J. G. (2018). Complex Evolutionary History of Translation Elongation Factor 2 and Diphthamide Biosynthesis in Archaea and Parabasalids. Genome Biology and Evolution, 10(9), 2380-2393
Open this publication in new window or tab >>Complex Evolutionary History of Translation Elongation Factor 2 and Diphthamide Biosynthesis in Archaea and Parabasalids
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2018 (English)In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 10, no 9, p. 2380-2393Article in journal (Refereed) Published
Abstract [en]

Diphthamide is a modified histidine residue which is uniquely present in archaeal and eukaryotic elongation factor 2 (EF-2), an essential GTPase responsible for catalyzing the coordinated translocation of tRNA and mRNA through the ribosome. In part due to the role of diphthamide in maintaining translational fidelity, it was previously assumed that diphthamide biosynthesis genes (dph) are conserved across all eukaryotes and archaea. Here, comparative analysis of new and existing genomes reveals that some archaea (i.e., members of the Asgard superphylum, Geoarchaea, and Korarchaeota) and eukaryotes (i.e., parabasalids) lack dph. In addition, while EF-2 was thought to exist as a single copy in archaea, many of these dph-lacking archaeal genomes encode a second EF-2 paralog missing key residues required for diphthamide modification and for normal translocase function, perhaps suggesting functional divergence linked to loss of diphthamide biosynthesis. Interestingly, some Heimdallarchaeota previously suggested to be most closely related to the eukaryotic ancestor maintain dph genes and a single gene encoding canonical EF-2. Our findings reveal that the ability to produce diphthamide, once thought to be a universal feature in archaea and eukaryotes, has been lost multiple times during evolution, and suggest that anticipated compensatory mechanisms evolved independently.

Keywords
Asgard, Korarchaeota, Trichomonas, metagenomics, EF-2, diphthamide
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-368041 (URN)10.1093/gbe/evy154 (DOI)000446102700018 ()30060184 (PubMedID)
Funder
EU, European Research Council, 310039-PUZZLE_CELLSwedish Foundation for Strategic Research , SSF-FFL5Swedish Research Council, 2015-04959
Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2018-12-03Bibliographically approved
Leger, M. M., Eme, L., Stairs, C. W. & Roger, A. J. (2018). Demystifying Eukaryote Lateral Gene Transfer. Bioessays, 40(5), Article ID 1700242.
Open this publication in new window or tab >>Demystifying Eukaryote Lateral Gene Transfer
2018 (English)In: Bioessays, ISSN 0265-9247, E-ISSN 1521-1878, Vol. 40, no 5, article id 1700242Article in journal (Refereed) Published
Abstract [en]

In a recent BioEssays paper [W. F. Martin, BioEssays 2017, 39, 1700115], William Martin sharply criticizes evolutionary interpretations that involve lateral gene transfer (LGT) into eukaryotic genomes. Most published examples of LGTs in eukaryotes, he suggests, are in fact contaminants, ancestral genes that have been lost from other extant lineages, or the result of artefactual phylogenetic inferences. Martin argues that, except for transfers that occurred from endosymbiotic organelles, eukaryote LGT is insignificant. Here, in reviewing this field, we seek to correct some of the misconceptions presented therein with regard to the evidence for LGT in eukaryotes.

Keywords
eukaryote genomes, horizontal gene transfer, lateral gene transfer
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-353361 (URN)10.1002/bies.201700242 (DOI)000430463500006 ()29543982 (PubMedID)
Funder
EU, European Research Council, ERC-2012-Co-616960]EU, Horizon 2020, 704263]
Available from: 2018-06-12 Created: 2018-06-12 Last updated: 2018-08-21Bibliographically approved
Eme, L., Spang, A., Lombard, J., Stairs, C. W. & Ettema, T. J. G. (2017). Archaea and the origin of eukaryotes. Nature Reviews Microbiology, 15(12), 711-723
Open this publication in new window or tab >>Archaea and the origin of eukaryotes
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2017 (English)In: Nature Reviews Microbiology, ISSN 1740-1526, E-ISSN 1740-1534, Vol. 15, no 12, p. 711-723Article, review/survey (Refereed) Published
Abstract [en]

Woese and Fox's 1977 paper on the discovery of the Archaea triggered a revolution in the field of evolutionary biology by showing that life was divided into not only prokaryotes and eukaryotes. Rather, they revealed that prokaryotes comprise two distinct types of organisms, the Bacteria and the Archaea. In subsequent years, molecular phylogenetic analyses indicated that eukaryotes and the Archaea represent sister groups in the tree of life. During the genomic era, it became evident that eukaryotic cells possess a mixture of archaeal and bacterial features in addition to eukaryotic-specific features. Although it has been generally accepted for some time that mitochondria descend from endosymbiotic alphaproteobacteria, the precise evolutionary relationship between eukaryotes and archaea has continued to be a subject of debate. In this Review, we outline a brief history of the changing shape of the tree of life and examine how the recent discovery of a myriad of diverse archaeal lineages has changed our understanding of the evolutionary relationships between the three domains of life and the origin of eukaryotes. Furthermore, we revisit central questions regarding the process of eukaryogenesis and discuss what can currently be inferred about the evolutionary transition from the first to the last eukaryotic common ancestor.

National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-341027 (URN)10.1038/nrmicro.2017.133 (DOI)000414858500007 ()29123225 (PubMedID)
Note

Correction in: Nature Reviews Microbiology, Volume: 16, Issue: 2, Page: 121, DOI: 10.1038/nrmicro.2017.154

Available from: 2018-02-06 Created: 2018-02-06 Last updated: 2018-08-21Bibliographically approved
Gentekaki, E., Curtis, B. A., Stairs, C. W., Klimes, V., Elias, M., Salas-Leiva, D. E., . . . Roger, A. J. (2017). Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis. PLoS biology, 15(9), Article ID e2003769.
Open this publication in new window or tab >>Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis
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2017 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 15, no 9, article id e2003769Article in journal (Refereed) Published
Abstract [en]

Blastocystis is the most prevalent eukaryotic microbe colonizing the human gut, infecting approximately 1 billion individuals worldwide. Although Blastocystis has been linked to intestinal disorders, its pathogenicity remains controversial because most carriers are asymptomatic. Here, the genome sequence of Blastocystis subtype (ST) 1 is presented and compared to previously published sequences for ST4 and ST7. Despite a conserved core of genes, there is unexpected diversity between these STs in terms of their genome sizes, guanine-cytosine (GC) content, intron numbers, and gene content. ST1 has 6,544 protein-coding genes, which is several hundred more than reported for ST4 and ST7. The percentage of proteins unique to each ST ranges from 6.2% to 20.5%, greatly exceeding the differences observed within parasite genera. Orthologous proteins also display extreme divergence in amino acid sequence identity between STs (i.e., 59%-61% median identity), on par with observations of the most distantly related species pairs of parasite genera. The STs also display substantial variation in gene family distributions and sizes, especially for protein kinase and protease gene families, which could reflect differences in virulence. It remains to be seen to what extent these inter-ST differences persist at the intra-ST level. A full 26% of genes in ST1 have stop codons that are created on the mRNA level by a novel polyadenylation mechanism found only in Blastocystis. Reconstructions of pathways and organellar systems revealed that ST1 has a relatively complete membrane-trafficking system and a near-complete meiotic toolkit, possibly indicating a sexual cycle. Unlike some intestinal protistan parasites, Blastocystis ST1 has near-complete de novo pyrimidine, purine, and thiamine biosynthesis pathways and is unique amongst studied stramenopiles in being able to metabolize alpha-glucans rather than beta-glucans. It lacks all genes encoding heme-containing cytochrome P450 proteins. Predictions of the mitochondrion-related organelle (MRO) proteome reveal an expanded repertoire of functions, including lipid, cofactor, and vitamin biosynthesis, as well as proteins that may be involved in regulating mitochondrial morphology and MRO/endoplasmic reticulum (ER) interactions. In sharp contrast, genes for peroxisome-associated functions are absent, suggesting Blastocystis STs lack this organelle. Overall, this study provides an important window into the biology of Blastocystis, showcasing significant differences between STs that can guide future experimental investigations into differences in their virulence and clarifying the roles of these organisms in gut health and disease.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2017
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-336835 (URN)10.1371/journal.pbio.2003769 (DOI)000411978200015 ()28892507 (PubMedID)
Funder
Wellcome trust
Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2018-08-21Bibliographically approved
Leger, M. M., Kolisko, M., Kamikawa, R., Stairs, C. W., Kume, K., Cepicka, I., . . . Roger, A. J. (2017). Organelles that illuminate the origins of Trichomonas hydrogenosomes and Giardia mitosomes. NATURE ECOLOGY & EVOLUTION, 1(4), Article ID UNSP 0092.
Open this publication in new window or tab >>Organelles that illuminate the origins of Trichomonas hydrogenosomes and Giardia mitosomes
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2017 (English)In: NATURE ECOLOGY & EVOLUTION, ISSN 2397-334X, Vol. 1, no 4, article id UNSP 0092Article in journal (Refereed) Published
Abstract [en]

Many anaerobic microbial parasites possess highly modified mitochondria known as mitochondrion-related organelles (MROs). The best-studied of these are the hydrogenosomes of Trichomonas vaginalis and Spironucleus salmonicida, which produce ATP anaerobically through substrate-level phosphorylation with concomitant hydrogen production; and the mitosomes of Giardia intestinalis, which are functionally reduced and lack any role in ATP production. Howewer, to understand the metabolic specializations that these MROs underwent in adaptation to parasitism, data from their free-living relatives are needed. Here, we present a large-scale comparative transcriptomic study of MROs across a major eukaryotic group, Metamonada, examining lineage-specific gain and loss of metabolic functions in the MROs of Trichomonas, Giardia, Spironucleus and their free-living relatives. Our analyses uncover a complex history of ATP production machinery in diplomonads such as Giardia, and their closest relative, Dysnectes; and a correlation between the glycine cleavage machinery and lifestyles. Our data further suggest the existence of a previously undescribed biochemical class of MRO that generates hydrogen but is incapable of ATP synthesis.

National Category
Microbiology Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-344540 (URN)10.1038/s41559-017-0092 (DOI)000417171500014 ()28474007 (PubMedID)
Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-08-21Bibliographically approved
Astvaldsson, A., Stairs, C. W., Xu, F., Haag, L., Alfjorden, A., Jansson, E., . . . Svärd, S. Dual transcriptomic analysis of Spironucleus salmonicida-infected salmon cells identifies putative virulence factors and host responses.
Open this publication in new window or tab >>Dual transcriptomic analysis of Spironucleus salmonicida-infected salmon cells identifies putative virulence factors and host responses
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(English)Manuscript (preprint) (Other academic)
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-379666 (URN)
Available from: 2019-03-19 Created: 2019-03-19 Last updated: 2019-03-19
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