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Jerlstrom-Hultqvist, Joel
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Publications (10 of 14) Show all publications
Jerlström-Hultqvist, J., Warsi, O., Söderholm, A., Knopp, M., Eckhard, U., Vorontsov, E., . . . Andersson, D. I. (2018). A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function. Nature Ecology & Evolution, 2(8), 1321-1330
Open this publication in new window or tab >>A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function
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2018 (English)In: Nature Ecology & Evolution, E-ISSN 2397-334X, Vol. 2, no 8, p. 1321-1330Article in journal (Refereed) Published
Abstract [en]

One key concept in the evolution of new functions is the ability of enzymes to perform promiscuous side-reactions that serve as a source of novelty that may become beneficial under certain conditions. Here, we identify a mechanism where a bacteriophage-encoded enzyme introduces novelty by inducing expression of a promiscuous bacterial enzyme. By screening for bacteriophage DNA that rescued an auxotrophic Escherichia coli mutant carrying a deletion of the ilvA gene, we show that bacteriophage-encoded S-adenosylmethionine (SAM) hydrolases reduce SAM levels. Through this perturbation of bacterial metabolism, expression of the promiscuous bacterial enzyme MetB is increased, which in turn complements the absence of IlvA. These results demonstrate how foreign DNA can increase the metabolic capacity of bacteria, not only by transfer of bona fide new genes, but also by bringing cryptic bacterial functions to light via perturbations of cellular physiology.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Evolutionary Biology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-355286 (URN)10.1038/s41559-018-0568-5 (DOI)000439505600024 ()
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2018-06-27 Created: 2018-06-27 Last updated: 2018-11-22Bibliographically approved
Einarsson, E., Ástvaldsson, Á., Hultenby, K., Andersson, J. O., Svärd, S. G. & Jerlstrom-Hultqvist, J. (2016). Comparative cell biology and evolution of Annexins in Diplomonads. MSphere, 1(2), Article ID e00032-15.
Open this publication in new window or tab >>Comparative cell biology and evolution of Annexins in Diplomonads
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2016 (English)In: MSphere, ISSN 2379-5042, Vol. 1, no 2, article id e00032-15Article in journal (Refereed) Published
Abstract [en]

Annexins are multifunctional, calcium-binding proteins found in organisms across all kingdoms. Most studies of annexins from single-celled eukaryotes have focused on the alpha-giardins, proteins assigned to the group E annexins, expressed by the diplomonad Giardia intestinalis. We have characterized the annexin gene family in another diplomonad parasite, Spironucleus salmonicida, by phylogenetic and experimental approaches. We constructed a comprehensive phylogeny of the diplomonad group E annexins and found that they are abundant across the group with frequent gene duplications and losses. The annexins of S. salmonicida were found to be related to alpha-giardins but with better-preserved type II Ca2+ coordination sites. Two annexins were confirmed to bind phospholipids in a Ca2+-dependent fashion but with different specificities. Superresolution and confocal microscopy of epitope-tagged S. salmonicida annexins revealed localization to distinct parts of the cytoskeleton and membrane. The ultrastructural details of the localization of several annexins were determined by proximity labeling and transmission electron microscopy. Two annexins localize to a novel cytoskeletal structure in the anterior of the cell. Our results show that the annexin gene family is expanded in diplomonads and that these group E annexins are associated mostly with cytoskeletal and membrane structures. IMPORTANCE Annexins are proteins that associate with phospholipids in a Ca2+-dependent fashion. These proteins have been intensely studied in animals and plants because of their importance in diverse cellular processes, yet very little is known about annexins in single-celled eukaryotes, which represent the largest diversity of organisms. The human intestinal parasite Giardia intestinalis is known to have more annexins than humans, and they contribute to its pathogenic potential. In this study, we investigated the annexin complement in the salmon pathogen Spironucleus salmonicida, a relative of G. intestinalis. We found that S. salmonicida has a large repertoire of annexins and that the gene family has expanded separately across diplomonads, with members showing sequence diversity similar to that seen across kingdom-level groups such as plants and animals. S. salmonicida annexins are prominent components of the cytoskeleton and membrane. Two annexins are associated with a previously unrecognized structure in the anterior of the cell.

Place, publisher, year, edition, pages
Uppsala: , 2016
Keywords
intestinal parasite, annexins, diplomonad, Spironucleus salmonicida, Giardia, proximity labeling, APEX
National Category
Cell Biology Microbiology Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-264537 (URN)10.1128/mSphere.00032-15 (DOI)000392584700008 ()
Funder
Swedish Research Council, 2012-3364Swedish Research Council Formas, 2013-910
Available from: 2015-10-14 Created: 2015-10-14 Last updated: 2019-03-19Bibliographically approved
Ankarklev, J., Franzen, O., Peirasmaki, D., Jerlstrom-Hultqvist, J., Lebbad, M., Andersson, J., . . . Svärd, S. G. (2015). Comparative genomic analyses of freshly isolated Giardia intestinalis assemblage A isolates. BMC Genomics, 16, Article ID 697.
Open this publication in new window or tab >>Comparative genomic analyses of freshly isolated Giardia intestinalis assemblage A isolates
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2015 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, article id 697Article in journal (Refereed) Published
Abstract [en]

Background: The diarrhea-causing protozoan Giardia intestinalis makes up a species complex of eight different assemblages (A-H), where assemblage A and B infect humans. Comparative whole-genome analyses of three of these assemblages have shown that there is significant divergence at the inter-assemblage level, however little is currently known regarding variation at the intra-assemblage level. We have performed whole genome sequencing of two sub-assemblage AII isolates, recently axenized from symptomatic human patients, to study the biological and genetic diversity within assemblage A isolates. Results: Several biological differences between the new and earlier characterized assemblage A isolates were identified, including a difference in growth medium preference. The two AII isolates were of different sub-assemblage types (AII-1 [AS175] and AII-2 [AS98]) and showed size differences in the smallest chromosomes. The amount of genetic diversity was characterized in relation to the genome of the Giardia reference isolate WB, an assemblage AI isolate. Our analyses indicate that the divergence between AI and AII is approximately 1 %, represented by similar to 100,000 single nucleotide polymorphisms (SNP) distributed over the chromosomes with enrichment in variable genomic regions containing surface antigens. The level of allelic sequence heterozygosity (ASH) in the two AII isolates was found to be 0.25-0.35 %, which is 25-30 fold higher than in the WB isolate and 10 fold higher than the assemblage AII isolate DH (0.037 %). 35 protein-encoding genes, not found in the WB genome, were identified in the two AII genomes. The large gene families of variant-specific surface proteins (VSPs) and high cysteine membrane proteins (HCMPs) showed isolate-specific divergences of the gene repertoires. Certain genes, often in small gene families with 2 to 8 members, localize to the variable regions of the genomes and show high sequence diversity between the assemblage A isolates. One of the families, Bactericidal/ Permeability Increasing-like protein (BPIL), with eight members was characterized further and the proteins were shown to localize to the ER in trophozoites. Conclusions: Giardia genomes are modular with highly conserved core regions mixed up by variable regions containing high levels of ASH, SNPs and variable surface antigens. There are significant genomic variations in assemblage A isolates, in terms of chromosome size, gene content, surface protein repertoire and gene polymorphisms and these differences mainly localize to the variable regions of the genomes. The large genetic differences within one assemblage of G. intestinalis strengthen the argument that the assemblages represent different Giardia species.

National Category
Genetics Microbiology
Identifiers
urn:nbn:se:uu:diva-264039 (URN)10.1186/s12864-015-1893-6 (DOI)000361093400009 ()26370391 (PubMedID)
Funder
Swedish Research Council FormasSwedish Research Council
Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2019-04-19Bibliographically approved
Andersson, D. I., Jerlström-Hultqvist, J. & Näsvall, J. (2015). Evolution of New Functions De Novo and from Preexisting Genes. Cold Spring Harbor Perspectives in Biology, 7(6), Article ID a017996.
Open this publication in new window or tab >>Evolution of New Functions De Novo and from Preexisting Genes
2015 (English)In: Cold Spring Harbor Perspectives in Biology, ISSN 1943-0264, E-ISSN 1943-0264, Vol. 7, no 6, article id a017996Article, review/survey (Refereed) Published
Abstract [en]

How the enormous structural and functional diversity of new genes and proteins was generated (estimated to be 10^10-€“10^12 different proteins in all organisms on earth [Choi I-G, Kim S-H. 2006. Evolution of protein structural classes and protein sequence families. Proc Natl Acad Sci 103: 14056–14061] is a central biological question that has a long and rich history. Extensive work during the last 80 years have shown that new genes that play important roles in lineage-specific phenotypes and adaptation can originate through a multitude of different mechanisms, including duplication, lateral gene transfer, gene fusion/fission, and de novo origination. In this review, we focus on two main processes as generators of new functions: evolution of new genes by duplication and divergence of pre-existing genes and de novo gene origination in which a whole protein-coding gene evolves from a noncoding sequence.

National Category
Evolutionary Biology
Research subject
Biology with specialization in Molecular Evolution
Identifiers
urn:nbn:se:uu:diva-253740 (URN)10.1101/cshperspect.a017996 (DOI)000358241300006 ()
Funder
Swedish Research Council
Available from: 2015-06-02 Created: 2015-06-02 Last updated: 2017-12-04Bibliographically approved
Xu, F., Jerlström-Hultqvist, J., Einarsson, E., Astvaldsson, A., Svärd, S. G. & Andersson, J. O. (2014). The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments. PLoS Genetics, 10(2), e1004053
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, p. e1004053-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
Identifiers
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: 2019-03-19Bibliographically approved
Jerlström-Hultqvist, J., Einarsson, E., Xu, F., Hjort, K., Ek, B., Steinhauf, D., . . . Svärd, S. G. (2013). Hydrogenosomes in the diplomonad Spironucleus salmonicida. Nature Communications, 4, 2493
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, E-ISSN 2041-1723, Vol. 4, p. 2493-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
Identifiers
urn:nbn:se:uu:diva-210741 (URN)10.1038/ncomms3493 (DOI)000325534300002 ()
Available from: 2013-11-14 Created: 2013-11-14 Last updated: 2017-12-06Bibliographically approved
Franzén, O., Jerlström-Hultqvist, J., Einarsson, E., Ankarklev, J., Ferella, M., Andersson, B. & Svärd, S. (2013). Transcriptome Profiling of Giardia intestinalis Using Strand-specific RNAseq. PloS Computational Biology, 9(3), Article ID e1003000.
Open this publication in new window or tab >>Transcriptome Profiling of Giardia intestinalis Using Strand-specific RNAseq
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2013 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 9, no 3, article id e1003000Article in journal (Refereed) Published
Abstract [en]

Giardia intestinalis is a common cause of diarrheal disease and it consists of eight genetically distinct genotypes or assemblages (A-H). Only assemblages A and B infect humans and are suggested to represent two different Giardia species. Correlations exist between assemblage type and host-specificity and to some extent symptoms. Phenotypical differences have been documented between assemblages and genome sequences are available for A, B and E. We have characterized and compared the polyadenylated transcriptomes of assemblages A, B and E. Four genetically different isolates were studied (WB (AI), AS175 (AII), P15 (E) and GS (B)) using paired-end, strand-specific RNA-seq. Most ofthe genome was transcribed in trophozoites grown in vitro, but at vastly different levels.RNA-seq confirmed many of the present annotations and refined the current genome annotation. Gene expression divergence was found to recapitulate the known phylogeny, and uncovered lineage-specific differences in expression. Polyadenylation sites were mapped for over 70% of the genes and revealed many examples of conserved and unexpectedly long 3' UTRs. 28 open reading frames were found in a non-transcribed gene cluster on chromosome 5 of the WB isolate. Analysis of allele-specific expression revealed a correlation between allele-dosage and allele expression in the GS isolate. Previously reported cis-splicing events were confirmed and global mapping of cis-splicing identified only one novel intron. These observations can possibly explain differences in host-preference and symptoms, and it will be the basis for further studies of Giardia pathogenesis and biology.

Keywords
Giardia intestinalis, transcriptome, RNA-seq, poly(A), intestinal parasite
National Category
Microbiology Infectious Medicine
Research subject
Biology with specialization in Microbiology; Biology with specialization in Evolutionary Organismal Biology
Identifiers
urn:nbn:se:uu:diva-182829 (URN)10.1371/journal.pcbi.1003000 (DOI)000316864200066 ()
Available from: 2012-10-16 Created: 2012-10-16 Last updated: 2017-12-07Bibliographically approved
Xu, F., Jerlström-Hultqvist, J. & Andersson, J. O. (2012). Genome-Wide Analyses of Recombination Suggest That Giardia intestinalis Assemblages Represent Different Species. Molecular biology and evolution, 29(10), 2895-2898
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, p. 2895-2898Article 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
Identifiers
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: 2017-12-07Bibliographically approved
Jerlström-Hultqvist, J. (2012). Hidden Diversity Revealed: Genomic, Transcriptomic and Functional Studies of Diplomonads. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
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. p. 104
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 990
Keywords
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
Identifiers
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)
Opponent
Supervisors
Available from: 2012-11-22 Created: 2012-10-16 Last updated: 2013-02-11Bibliographically approved
Hertz, H. M., von Hofsten, O., Bertilson, M., Vogt, U., Holmberg, A., Reinspach, J., . . . Svärd, S. (2012). Laboratory cryo soft X-ray microscopy. Journal of Structural Biology, 177(2), 267-272
Open this publication in new window or tab >>Laboratory cryo soft X-ray microscopy
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2012 (English)In: Journal of Structural Biology, ISSN 1047-8477, E-ISSN 1095-8657, Vol. 177, no 2, p. 267-272Article in journal (Refereed) Published
Abstract [en]

Lens-based water-window X-ray microscopy allows two- and three-dimensional (2D and 3D) imaging of intact unstained cells in their near-native state with unprecedented contrast and resolution. Cryofixation is essential to avoid radiation damage to the sample. Present cryo X-ray microscopes rely on synchrotron radiation sources, thereby limiting the accessibility for a wider community of biologists. In the present paper we demonstrate water-window cryo X-ray microscopy with a laboratory-source-based arrangement. The microscope relies on a lambda = 2.48-nm liquid-jet high-brightness laser-plasma source, normal-incidence multilayer condenser optics, 30-nm zone-plate optics, and a cryo sample chamber. We demonstrate 2D imaging of test patterns, and intact unstained yeast, protozoan parasites and mammalian cells. Overview 3D information is obtained by stereo imaging while complete 3D microscopy is provided by full tomographic reconstruction. The laboratory microscope image quality approaches that of the synchrotron microscopes, but with longer exposure times. The experimental image quality is analyzed from a numerical wave-propagation model of the imaging system and a path to reach synchrotron-like exposure times in laboratory microscopy is outlined.

Keywords
X-ray microscopy, Cryo fixation, Laboratory, Parasites
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-171685 (URN)10.1016/j.jsb.2011.11.015 (DOI)000300755400011 ()
Available from: 2012-03-26 Created: 2012-03-25 Last updated: 2017-12-07Bibliographically approved
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