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  • 12951.
    Zomorodipour, Alireza
    Uppsala University, Department of Molecular Biology.
    Mapping the Rickettsia prowazekii genome1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rickettsia prowazekii is a member of alpha proteobacteria and the etiologic agent of epidemictyphus. Besides its pathogenicity as an obligate intracellular parasite it has been considered as amodel organism in a variety of studies.

    We have established a collection of overlapping clones, covering nearly the complete R.prowazekii genome. The clones were isolated from three genomic libraries in cosmid, lambdaphage and lambda-Zap vectors and arranged along the entire genome, using a bottom-upmethod. The ordered genomic libraries have served an important function in the sequencing ofthe entire genome and will be useful for further functional studies of the R. prowazekii genes.

    The sequencing and analysis of the entire R. prowazekii genome have provided evidencefor an exclusive obligate intracellular parasite with massive genomic reduction and a generalgenomic rearrangement in addition to an unusually high fraction (24%) of non-coding regions.There is evidence to suggest that the non-coding regions may be remnants of genes which areeliminated from the genome in an on-going process of genomic reduction. The genomicrearrangements are likely to have occurred through intra-chromosomal recombination events,mediated by repeated sequences in the ancestral genome which might have been deletedsubsequently. The rearrangement of the genome was evidenced in our earlier work whichdetected that the single copy of the 16S rRNA gene is located distantly from the linked 23S-5SrRNA genes in the R. prowazekii genome.

    Phylogenetic analysis based on a large number of R. prowazekii genes indicates that R.prowazekii is more closely related to mitochondria than any other microbial genome. Theobtained results are in accordance with the previously obtained data which was based onphylogentic analysis of rRNA genes. The partial similarities in gene composition between R.prowazekii and mitochondrial genomes is also additional evidence for this relationship.

    A comparative analysis between the complete genomes of the R. prowazekii and theChlamydia trachomatis, a distantly related obligate intracellular parasite, uncovered a total of325 genes with significant homology between the two genomes. A similar pattern of reductionin the corresponding functional categories is observed between these two genomes. Duringadaptation to their eukaryotic nutrient-rich environment, the two parasitic bacteria haveundergone a massive genomic loss and became more dependent on a host. In compensation,they have developed systems such as transporters that can exploit host cell provided nutrients.The comparative analysis has provided additional evidence for a convergent evolution duringadaptation to an intracellular life style in two distantly related bacteria.

  • 12952.
    Zorzet, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pavlov, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Nilsson, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ehrenberg, Måns
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Andersson, Dan I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Error-prone initiation factor 2 mutations reduce the fitness cost of antibiotic resistance2010In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, ISSN 20132454, Vol. 75, no 5, p. 1299-1313Article in journal (Refereed)
    Abstract [en]

    Mutations in the fmt gene (encoding formyl methionine transferase) that eliminate formylation of initiator tRNA (Met-tRNA(i)) confer resistance to the novel antibiotic class of peptide deformylase inhibitors (PDFIs) while concomitantly reducing bacterial fitness. Here we show in Salmonella typhimurium that novel mutations in initiation factor 2 (IF2) located outside the initiator tRNA binding domain can partly restore fitness of fmt mutants without loss of antibiotic resistance. Analysis of initiation of protein synthesis in vitro showed that with non-formylated Met-tRNA(i) IF2 mutants initiated much faster than wild-type IF2, whereas with formylated fMet-tRNA(i) the initiation rates were similar. Moreover, the increase in initiation rates with Met-tRNA(i) conferred by IF2 mutations in vitro correlated well with the increase in growth rate conferred by the same mutations in vivo, suggesting that the mutations in IF2 compensate formylation deficiency by increasing the rate of in vivo initiation with Met-tRNA(i). IF2 mutants had also a high propensity for erroneous initiation with elongator tRNAs in vitro, which could account for their reduced fitness in vivo in a formylation-proficient strain. More generally, our results suggest that bacterial protein synthesis is mRNA-limited and that compensatory mutations in IF2 could increase the persistence of PDFI-resistant bacteria in clinical settings.

  • 12953.
    Zou, J
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Hallberg, BM
    Bergfors, T
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Oesch, F
    Arand, M
    Mowbray, S
    Jones, TA
    Structure of Aspergillus niger epoxide hydrolase at 1.8A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolyases2000In: Structure, Vol. 8, no 2, p. 111-122Article in journal (Refereed)
  • 12954.
    Zou, JY
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Molecular Biology.
    Jones, TA
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Molecular Biology.
    Towards the automatic interpretation of macromolecular electron-density maps: Qualitative and quantitative matching of protein sequence to map1996In: Acta Crystallographica Section D: Biological Crystallography, ISSN 0907-4449, E-ISSN 1399-0047, Vol. 52, p. 833-841Article in journal (Refereed)
    Abstract [en]

    The matching of the known polypeptide sequence to the electron density is a critical step in solving protein structures by the crystallographic method. Tools have been developed to help in defining the placement of the sequence, both qualitatively and quantitatively. They have been tested with good results on two proteins whose structures were solved by the MIR method.

  • 12955.
    Zou, JY
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Kleywegt, GJ
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Stahlberg, J
    Driguez, H
    Nerinckx, W
    Claeyssens, M
    Koivula, A
    Teerii, TT
    Jones, TA
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Crystallographic evidence for substrate ring distortion and protein conformational changes during catalysis in cellobiohydrolase Cel6A from Trichoderma reesei1999In: STRUCTURE WITH FOLDING & DESIGN, ISSN 0969-2126, Vol. 7, no 9, p. 1035-1045Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cel6A is one of the two cellobiohydrolases produced by Trichoderma reesei. The catalytic core has a structure that is a variation of the classic TIM barrel. The active site is located inside a tunnel, the roof of which is formed mainly by a pair of loops. RESULTS: We describe three new ligand complexes. One is the structure of the wild-type enzyme in complex with a nonhydrolysable cello-oligosaccharide, methyl 4-S-beta-cellobiosyl-4-thio-beta-cellobioside (Glc)(2)-S-(Glc)(2), which differs from a cellotetraose in the nature of the central glycosidic linkage where a sulphur atom replaces an oxygen atom. The second structure is a mutant, Y169F, in complex with the same ligand, and the third is the wild-type enzyme in complex with m-iodobenzyl beta-D-glucopyranosyl-beta(1,4)-D-xylopyranoside (IBXG). CONCLUSIONS: The (Glc)(2)-S-(Glc)(2) ligand binds in the -2 to +2 sites in both the wild-type and mutant enzymes. The glucosyl unit in the -1 site is distorted from the usual chair conformation in both structures. The IBXG ligand binds in the -2 to +1 sites, with the xylosyl unit in the -1 site where it adopts the energetically favourable chair conformation. The -1 site glucosyl of the (Glc)(2)-S-(Glc)(2) ligand is unable to take on this conformation because of steric clashes with the protein. The crystallographic results show that one of the tunnel-forming loops in Cel6A is sensitive to modifications at the active site, and is able to take on a number of different conformations. One of the conformational changes disrupts a set of interactions at the active site that we propose is an integral part of the reaction mechanism.

  • 12956.
    Zu, Pengjuan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Effects of Nectar Production and Pollinator Assemblies on Mating Patterns in Orchids2011Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Pollinator visitation patterns should affect pollination success and mating patterns in flowering species. In the orchid family, about one third of the species do not provide any reward for their pollinators. Pollination by deceit is typically associated with low fruit set but may increase the chance of cross-pollination since the pollinator should soon leave the individual plant when there is no reward in the flowers. This may be beneficial if self-fertilisation results in inbreeding depression. I studied the mating patterns of one rewarding and one deceptive orchid in two closely related genera by tracking the fate of stained pollinia. I also conducted controlled crosses to estimate inbreeding depression. The results show that the deceptive orchid Dactylorhiza lapponica has lower pollination success, but higher cross-pollination rate (ca. 90%) than the nectariferous orchid Gymnadenia conopsea (ca. 18% cross-pollination). The results further suggest that in G. conopsea, nocturnal visitors mediate higher geitonogamous pollination rate (ca. 100%) than diurnal visitors (ca. 60%). In both study species, fruits produced from cross-pollination were heavier than fruits produced from selfing. Inbreeding depression for fruit mass did not differ significantly between the two species (δ = 0.21 in D. lapponica and δ = 0.29 in G. conopsea). These data support the hypothesis that pollination by deceit can enhance cross-pollination. A literature study including several rewarding and non-rewarding orchid species indicated lower geitonogamy in the deceptive orchids, but the difference was not statistically significant. 

  • 12957.
    Zubarev, Roman A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Nielsen, Michael L.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Fung, Eva M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Savitski, Mikhail M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Kel-Margoulis, Olga
    Wingender, Edgar
    Kel, Alexander
    Identification of dominant signaling pathways from proteomics expression data2008In: Journal of Proteomics, ISSN 1874-3919, Vol. 71, no 1, p. 89-96Article in journal (Refereed)
    Abstract [en]

    The availability of the results of high-throughput analyses coming from 'omic' technologies has been one of the major driving forces of pathway biology. Analytical pathway biology strives to design a 'pathway search engine', where the input is the 'omic' data and the output is the list of activated or dominant pathways in a given sample. Here we describe the first attempt to design and validate such a pathway search engine using as input expression proteomics data. The engine represents a specific workflow in computational tools developed originally for mRNA analysis (BMC Bioinformatics 2006, 7 (Suppl 2), S13). Using our own datasets as well as data from recent proteomics literature we demonstrate that different dominant pathways (EGF, TGF(beta), stress, and Fas pathways) can be correctly identified even from limited datasets. Pathway search engines can find application in a variety of proteomics-related fields, from fundamental molecular biology to search for novel types of disease biomarkers.

  • 12958.
    Zubarev, Roman A
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Zubarev, Alexander R
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Savitski, Mikhail M
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Electron capture/transfer versus collisionally activated/induced dissociations: Solo or duet?2008In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 19, no 6, p. 753-761Article in journal (Refereed)
    Abstract [en]

    New ion fragmentation technologies-electron capture dissociation (ECD) and electron-transfer dissociation (ETD)-are based on interaction of multiply charged polypeptides with either free electrons (ECD) or anionic species (ETD). After initial difficulties, these ECD/ETD (ExD) technologies are now being increasingly implemented in high-throughput proteornics work. This critical analysis presents arguments for the combined use of ExD with the conventional low-energy collisional excitation CID/CAD (CxD). It is argued that the database search, a key technology in MS/MS-based proteomics, is vulnerable with respect to the incomplete sequence information obtainable with either of the techniques, peptide MS/MS homology being a major complicating factor. De novo sequencing is viewed as the only adequate answer to this challenge and it can be achieved only with combined use of ExD and CxD. The payoff in the form of additional sequence information is projected to exceed the costs of such implementation. The greatest impact of combining ExD and CxD is expected in high-resolution instruments.

  • 12959. Zuccolo, Andrea
    et al.
    Scofield, Douglas G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    De Paoli, Emanuele
    Morgante, Michele
    The Ty1-copia LTR retroelement family PARTC is highly conserved in conifers over 200 MY of evolution2015In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 568, no 1, p. 89-99Article in journal (Refereed)
    Abstract [en]

    Long Terminal Repeat retroelements (LTR-RTs) are a major component of many plant genomes. Although well studied and described in angiosperms, their features and dynamics are poorly understood in gymnosperms. Representative complete copies of a Ty1-copia element isolate in Picea abies and named PARTC were identified in six other conifer species (Picea glauca, Pinus sylvestris, Pinus taeda, Abies sibirica, Taxus baccata and Juniperus communis) covering more than 200 million years of evolution. Here we characterized the structure of this element, assessed its abundance across conifers, studied the modes and timing of its amplification, and evaluated the degree of conservation of its extant copies at nucleotide level over distant species. We demonstrated that the element is ancient, abundant, widespread and its paralogous copies are present in the genera Picea, Pinus and Abies as an LTR-RT family. The amplification leading to the extant copies of PARTC occurred over long evolutionary times spanning 10 s of MY and mostly took place after the speciation of the conifers analyzed. The level of conservation of PARTC is striking and may be explained by low substitution rates and limited removal mechanisms for LTR-RTs. These PARTC features and dynamics are representative of a more general scenario for LTR-RTs in gymnosperms quite different from that characterizing the vast majority of LTR-RT elements in angiosperms. (C) 2015 Elsevier B.V. All rights reserved.

  • 12960. Zwart, G.
    et al.
    van Hannen, E. J
    Kamst-van Agterveld, M. P.
    Van der Gucht, K.
    Lindström, E.S.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    van Wichelen, J.
    Lauridsen, T
    Crump, B. C.
    Han, S.-K.
    Declerck, S.
    Rapid Screening for Freshwater Bacterial Groups by Using Reverse Line Blot Hybridization2003In: Applied and Environmental Microbiology,, Vol. 69, p. 5875-5883Article in journal (Refereed)
  • 12961.
    Zwoinska, Martyna K.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Age-specific trade-offs in life-history evolution2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Trade-offs prevent selection from driving all fitness-enhancing traits towards values that would maximize fitness. Life-history trade-offs, such as the one between survival and reproduction are well-studied, yet trade-offs can also involve behavioural or cognitive traits. Because males and females have different routes to successful reproduction, the optimal resolution of life-history trade-offs can differ between the sexes. However, shared genome can constrain the evolution of sex-specific adaptations. In this thesis, I explore the links between sex-specific life histories, cognition and behaviour. I start by linking sex differences in life histories to sex differences in learning performance in the outcrossing nematode Caenorhabditis remanei (Paper I). I report that age-related learning differs between the sexes and that it corresponds to sexual dimorphism in life history. Then, I use experimental evolution to select for learning performance to study the patterns of genetic correlations between learning and life-history traits in both sexes (Paper II). The results demonstrate the correlated evolution of sexual dimorphism in life history indicating sex-specific fitness costs and benefits of learning. In Paper III I use the fruit fly Drosophila melanogaster to ask about the extent to which cognitive and demographic aging are independent. The results reveal that selection for late-life reproduction alone bears no effect on late-life learning and that joint selection on late-life learning and reproduction does not yield lifespan benefits. The selection might have affected, however, female age-specific reproductive effort. Motivated by the questions on aging I proceed to ask why a potent lifespan extending drug – rapamycin affects sexes differently (Paper IV). I take a closer look at the trade-off between growth, lifespan and reproduction and propose that the sex experiencing a stronger relationship between size and fitness pays a higher cost of lifespan extension. Finally, I focus on another sex-specific trait – dispersal (Paper V). I conduct experimental evolution to uncover a negative genetic correlation between dispersal and reproduction and show sex-specific genetic variation for dispersal. In summary, my thesis unravels the complex pattern of interdependence between life-history, behavioural and cognitive traits, where sex emerges as an important factor that can maintain genetic variation for trade-offs.

    List of papers
    1. Sex differences in cognitive ageing: Testing predictions derived from life-history theory in a dioecious nematode
    Open this publication in new window or tab >>Sex differences in cognitive ageing: Testing predictions derived from life-history theory in a dioecious nematode
    2013 (English)In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 48, no 12, p. 1469-1472Article in journal (Refereed) Published
    Abstract [en]

    Life-history theory maintains that organisms allocate limited resources to different traits to maximize fitness. Learning ability and memory are costly and known to trade-off with longevity in invertebrates. However, since the relationship between longevity and fitness often differs between the sexes, it is likely that sexes will differentially resolve the trade-off between learning and longevity. We used an established associative learning paradigm in the dioecious nematode Caenorhabditis remanei, which is sexually dimorphic for lifespan, to study age-related learning ability in males and females. In particular, we tested the hypothesis that females (the shorter-lived sex) show higher learning ability than males early in life but senesce faster. Indeed, young females outperformed young males in learning a novel association between an odour (butanone) and food (bacteria). However, while learning ability and offspring production declined rapidly with age in females, males maintained high levels of these traits until mid-age. These results not only demonstrate sexual dimorphismin age-related learning ability but also suggest that it conforms to predictions derived from the life-history theory.

    Keywords
    Ageing, Caenorhabditis, Learning, Life-history, Sex differences, Trade-off
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-213468 (URN)10.1016/j.exger.2013.09.008 (DOI)000327489800012 ()
    Available from: 2013-12-30 Created: 2013-12-23 Last updated: 2017-12-06Bibliographically approved
    2. Selection on learning performance results in the correlated evolution of sexual dimorphism in life history
    Open this publication in new window or tab >>Selection on learning performance results in the correlated evolution of sexual dimorphism in life history
    Show others...
    2016 (English)In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 70, no 2, p. 342-357Article in journal (Refereed) Published
    Abstract [en]

    The evolution of learning can be constrained by trade-offs. As male and female life histories often diverge, the relationship between learning and fitness may differ between the sexes. However, because sexes share much of their genome, intersexual genetic correlations can prevent males and females from reaching their sex-specific optima resulting in intralocus sexual conflict (IaSC). To investigate if IaSC constraints sex-specific evolution of learning, we selected Caenorhabditis remanei nematode females for increased or decreased olfactory learning performance and measured learning, life span (in mated and virgin worms), reproduction, and locomotory activity in both sexes. Males from downward-selected female lines had higher locomotory activity and longer virgin life span but sired fewer progeny than males from upward-selected female lines. In contrast, we found no effect of selection on female reproduction and downward-selected females showed higher locomotory activity but lived shorter as virgins than upward-selected females. Strikingly, selection on learning performance led to the reversal of sexual dimorphism in virgin life span. We thus show sex-specific trade-offs between learning, reproduction, and life span. Our results support the hypothesis that selection on learning performance can shape the evolution of sexually dimorphic life histories via sex-specific genetic correlations.

    Keywords
    Caenorhabditis, cognition, intralocus sexual conflict, olfactory learning, sex-specific life histories
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-282325 (URN)10.1111/evo.12862 (DOI)000370662500007 ()26787139 (PubMedID)
    Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30Bibliographically approved
    3. Experimental evolution of slowed cognitive aging in Drosophila melanogaster
    Open this publication in new window or tab >>Experimental evolution of slowed cognitive aging in Drosophila melanogaster
    2017 (English)In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 3, p. 662-670Article in journal (Refereed) Published
    Abstract [en]

    Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories.

    Place, publisher, year, edition, pages
    WILEY, 2017
    Keywords
    Cognitive aging, Drosophila, experimental evolution, genetic architecture, learning, trade-off
    National Category
    Genetics
    Identifiers
    urn:nbn:se:uu:diva-320841 (URN)10.1111/evo.13156 (DOI)000396039000011 ()28000915 (PubMedID)
    Funder
    The Royal Swedish Academy of SciencesSwedish Research CouncilEU, European Research Council
    Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2017-09-07Bibliographically approved
    4. Sex-specific Tradeoffs With Growth and Fitness Following Life-span Extension by Rapamycin in an Outcrossing Nematode, Caenorhabditis remanei
    Open this publication in new window or tab >>Sex-specific Tradeoffs With Growth and Fitness Following Life-span Extension by Rapamycin in an Outcrossing Nematode, Caenorhabditis remanei
    Show others...
    2016 (English)In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 71, no 7, p. 882-890Article in journal (Refereed) Published
    Abstract [en]

    Rapamycin inhibits the nutrient-sensing TOR pathway and extends life span in a wide range of organisms. Although life-span extension usually differs between the sexes, the reason for this is poorly understood. Because TOR influences growth, rapamycin likely affects life-history traits such as growth and reproduction. Sexes have different life-history strategies, and theory predicts that they will resolve the tradeoffs between growth, reproduction, and life span differently. Specifically, in taxa with female-biased sexual size dimorphism, reduced growth may have smaller effects on male fitness. We investigated the effects of juvenile, adult, or life-long rapamycin treatment on growth, reproduction, life span, and individual fitness in the outcrossing nematode Caenorhabditis remanei. Life-long exposure to rapamycin always resulted in the strongest response, whereas postreproductive exposure did not affect life span. Although rapamycin resulted in longer life span and smaller size in males, male individual fitness was not affected. In contrast, size and fitness were negatively affected in females, whereas life span was only extended under high rapamycin concentrations. Our results support the hypothesis that rapamycin affects key life-history traits in a sex-specific manner. We argue that the fitness cost of life-span extension will be sex specific and propose that the smaller sex generally pay less while enjoying stronger life-span increase.

    Keywords
    Antiaging, Evolution, Longevity
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-304528 (URN)10.1093/gerona/glv174 (DOI)000381209900006 ()26472877 (PubMedID)
    Funder
    Swedish Research Council, C0636601, 621-2013-4828EU, European Research Council, St-G 2010 AGINGSEXDIFF 260885
    Available from: 2016-10-12 Created: 2016-10-06 Last updated: 2017-11-29Bibliographically approved
    5. Fitness-associated dispersal: selection for increased dispersal results in lower fitness
    Open this publication in new window or tab >>Fitness-associated dispersal: selection for increased dispersal results in lower fitness
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    fitness-associated dispersal, dispersal syndromes, artificial selection, life-history theory, Caenorhabdtitis
    National Category
    Natural Sciences
    Research subject
    Biology with specialization in Animal Ecology
    Identifiers
    urn:nbn:se:uu:diva-329033 (URN)
    Available from: 2017-09-06 Created: 2017-09-06 Last updated: 2017-09-07
  • 12962.
    Zwoinska, Martyna K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Kolm, Niclas
    Maklakov, Alexei A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Sex differences in cognitive ageing: Testing predictions derived from life-history theory in a dioecious nematode2013In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 48, no 12, p. 1469-1472Article in journal (Refereed)
    Abstract [en]

    Life-history theory maintains that organisms allocate limited resources to different traits to maximize fitness. Learning ability and memory are costly and known to trade-off with longevity in invertebrates. However, since the relationship between longevity and fitness often differs between the sexes, it is likely that sexes will differentially resolve the trade-off between learning and longevity. We used an established associative learning paradigm in the dioecious nematode Caenorhabditis remanei, which is sexually dimorphic for lifespan, to study age-related learning ability in males and females. In particular, we tested the hypothesis that females (the shorter-lived sex) show higher learning ability than males early in life but senesce faster. Indeed, young females outperformed young males in learning a novel association between an odour (butanone) and food (bacteria). However, while learning ability and offspring production declined rapidly with age in females, males maintained high levels of these traits until mid-age. These results not only demonstrate sexual dimorphismin age-related learning ability but also suggest that it conforms to predictions derived from the life-history theory.

  • 12963.
    Zwoinska, Martyna K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Lind, Martin I.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Cortazar-Chinarro, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Ramsden, Mark
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Maklakov, Alexei A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Selection on learning performance results in the correlated evolution of sexual dimorphism in life history2016In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 70, no 2, p. 342-357Article in journal (Refereed)
    Abstract [en]

    The evolution of learning can be constrained by trade-offs. As male and female life histories often diverge, the relationship between learning and fitness may differ between the sexes. However, because sexes share much of their genome, intersexual genetic correlations can prevent males and females from reaching their sex-specific optima resulting in intralocus sexual conflict (IaSC). To investigate if IaSC constraints sex-specific evolution of learning, we selected Caenorhabditis remanei nematode females for increased or decreased olfactory learning performance and measured learning, life span (in mated and virgin worms), reproduction, and locomotory activity in both sexes. Males from downward-selected female lines had higher locomotory activity and longer virgin life span but sired fewer progeny than males from upward-selected female lines. In contrast, we found no effect of selection on female reproduction and downward-selected females showed higher locomotory activity but lived shorter as virgins than upward-selected females. Strikingly, selection on learning performance led to the reversal of sexual dimorphism in virgin life span. We thus show sex-specific trade-offs between learning, reproduction, and life span. Our results support the hypothesis that selection on learning performance can shape the evolution of sexually dimorphic life histories via sex-specific genetic correlations.

  • 12964.
    Zwoinska, Martyna K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology. Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland..
    Maklakov, Alexei A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Kawecki, Tadeusz J.
    Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland..
    Hollis, Brian
    Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.;Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland..
    Experimental evolution of slowed cognitive aging in Drosophila melanogaster2017In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 3, p. 662-670Article in journal (Refereed)
    Abstract [en]

    Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories.

  • 12965.
    Zwoinska, Martyna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Larva, Tuuli
    Sekajova, Zuzana
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Carlsson, Hanne
    Meurling, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Maklakov, Alexei
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Fitness-associated dispersal: selection for increased dispersal results in lower fitnessManuscript (preprint) (Other academic)
  • 12966.
    Zwoinska, Martyna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Lind, Martin I.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Maklakov, Alexei A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Sexual Conflict: Male Control of Female Longevity2014In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 24, no 5, p. R196-R198Article in journal (Other academic)
  • 12967. Zyla, Dagmara
    et al.
    Wegierek, Piotr
    Owocki, Krzysztof
    Niedzwiedzki, Grzegorz
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Insects and crustaceans from the latest Early-early Middle Triassic of Poland2013In: Palaeogeography, Palaeoclimatology, Palaeoecology, ISSN 0031-0182, E-ISSN 1872-616X, Vol. 371, p. 136-144Article in journal (Refereed)
    Abstract [en]

    Two stratigraphical horizons in the Palegi clay-pit, a new Triassic paleontological site within Buntsandstein deposits (latest Olenekian-early Anisian in age) in the Holy Cross Mountains (Poland), have yielded arthropod faunas comprising ca. 400 fossil specimens assigned to two subphyla: Crustacea (class Branchiopoda and Maxillopoda) and Hexapoda (class Insecta). The Palegi arthropod assemblage is similar to that described from the Middle Triassic of France and Germany but is dominated by remains of conchostracans and cockroaches. This new fauna expands our knowledge of the latest Early-early Middle Triassic diversity of insects and freshwater arthropods in the Germanic Basin. The newly discovered fauna represents one of the oldest Mesozoic records of insects described from the Buntsandstein fades of Europe, and provides important information to better appreciate the process of ecosystem recovery after the Permian-Triassic extinction.

  • 12968.
    Zyubko, Tatyana
    et al.
    Skolkovo Inst Sci & Technol, Ctr Life Sci, Moscow, Russia; Peter Great St Petersburg Polytech Univ, St Petersburg, Russia.
    Serebryakova, Marina
    Skolkovo Inst Sci & Technol, Ctr Life Sci, Moscow, Russia; Lomonosov Moscow State Univ, AN Belozersky Inst Physicochem Biol, Moscow Russia; Russian Acad Sci, Inst Gene Biol, Moscow, Russia.
    Andreeva, Julia
    Skolkovo Inst Sci & Technol, Moscow, Russia; Russian Acad Sci, Moscow, Russia.
    Metelev, Mikhail
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology. Skolkovo Inst Sci & Technol, Moscow, Russia; Peter Great St Petersburg Polytech Univ, St Petersburg, Russia; Russian Acad Sci, Inst Gene Biol, Moscow Russia.
    Lippens, Guy
    Ups, INSA, INRA, TBI, CNRS, Toulouse, France.
    Dubiley, Svetlana
    Skolkovo Inst Sci & Technol, Moscow, Russia; Russian Acad Sci, Inst Gene Biol, Moscow, Russia.
    Severinov, Konstantin
    Skolkovo Inst Sci & Technol, Moscow, Russia; Waksman Inst Microbiol, Piscataway, NJ USA.
    Efficient in vivo synthesis of lasso peptide pseudomycoidin proceeds in the absence of both the leader and the leader peptidase2019In: Chemical Science, ISSN 2041-6520, E-ISSN 2041-6539, Vol. 10, no 42, p. 9699-9707Article in journal (Refereed)
    Abstract [en]

    Bacterial lasso peptides are made from linear ribosomally synthesized precursors by specific cleavage at the leader-core junction site of the precursor by a dedicated protease recognizing the leader, followed by cyclisation of the newly formed N-terminus of the core part with a side chain of the internal aspartic or glutamic residue catalyzed by a macrolactam synthetase. The resulting structure has a tail that is threaded and fixed inside the cycle formed. Here, we characterize a new lasso peptide, pseudomycoidin, encoded by Bacillus pseudomycoides DSM 12442. The most surprising and unique feature of pseudomycoidin is that it can be produced in vivo from the ribosomally synthesized core part by a macrolactam synthetase, in the absence of the leader protease. The minimalism of the pseudomycoidin synthesis system makes it a powerful model to generate pseudomycoidin-based lasso-peptide libraries and to study the poorly understood process of lasso formation. We detected two additional pseudomycoidin modifications: phosphorylation of a terminal residue that was previously observed in another lasso peptide, followed by glycosylation, which was not observed heretofore. We speculate that these bulky C-terminal modifications may help maintain the threaded lasso topology of the compound synthesized by the macrolactam synthetase.

  • 12969. Álvarez-Buylla, Elena R.
    et al.
    Ambrose, Barbara A.
    Flores-Sandoval, Eduardo
    Vergara-Silva, Francisco
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Physiological Botany.
    Englund, Marie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Physiological Botany.
    Garay-Arroyo, Adriana
    García-Ponce, Berenice
    de la Torre-Bárcena, Eduardo
    Espinosa-Matías, Silvia
    Martínez, Esteban
    Piñeyro-Nelson, Alma
    Engström, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Physiological Botany.
    Meyerowitz, Elliot M.
    B-Function Expression in the Flower Center Underlies the Homeotic Phenotype of Lacandonia schismatica (Triuridaceae)2010In: The Plant Cell, ISSN 1040-4651, E-ISSN 1532-298X, Vol. 22, no 11, p. 3543-3559Article in journal (Refereed)
    Abstract [en]

    Spontaneous homeotic transformations have been described in natural populations of both plants and animals, but little is known about the molecular-genetic mechanisms underlying these processes in plants. In the ABC model of floral organ identity in Arabidopsis thaliana, the B- and C-functions are necessary for stamen morphogenesis, and C alone is required for carpel identity. We provide ABC model-based molecular-genetic evidence that explains the unique inside-out homeotic floral organ arrangement of the monocotyledonous mycoheterotroph species Lacandonia schismatica (Triuridaceae) from Mexico. Whereas a quarter million flowering plant species bear central carpels surrounded by stamens, L. schismatica stamens occur in the center of the flower and are surrounded by carpels. The simplest explanation for this is that the B-function is displaced toward the flower center. Our analyses of the spatio-temporal pattern of B- and C-function gene expression are consistent with this hypothesis. The hypothesis is further supported by conservation between the B-function genes of L. schismatica and Arabidopsis, as the former are able to rescue stamens in Arabidopsis transgenic complementation lines, and Ls-AP3 and Ls-PI are able to interact with each other and with the corresponding Arabidopsis B-function proteins in yeast. Thus, relatively simple molecular modifications may underlie important morphological shifts in natural populations of extant plant taxa.

  • 12970.
    Álvarez-Castro, José M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Carlborg, Örjan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    A unified model for functional and statistical epistasis and its application in quantitative trait loci analysis2007In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 176, no 2, p. 1151-1167Article in journal (Refereed)
    Abstract [en]

    Interaction between genes, or epistasis, is found to be common and it is a key, concept for understanding adaptation and evolution of natural populations, response to selection in breeding programs, and determination of complex disease. Current]),, two independent classes of models are used to study epistasis. Statistical models focus on maintaining desired statistical properties for detection and estimation of genetic effects and for the decomposition of genetic variance using average effects of allele Substitutions in populations as parameters. Functional models focus on the evolutionary consequences of the attributes of the genotype-phenotype map using natural effects of allele substitutions as parameters. Here we provide a new, general and unified model framework: the natural and orthogonal interactions (NOIA) model. NOIA implements tools for transforming genetic effects measured in One Population to the ones of other populations (e.g., between two experimental designs for QTL) and parameters of statistical and functional epistasis into each other (thus enabling us to obtain functional estimates of QTL), as demonstrated numerically. We develop graphical interpretations of functional and statistical models as regressions of the genotypic values on the gene content, which illustrates the difference between the models-the constraint on the slope of the functional regression-and when the models are equivalent. Furthermore, we use our theoretical foundations to conceptually clarify functional and statistical epistasis, discuss the advantages of NOIA over previous theory, and stress the importance of linking functional and statistical models.

  • 12971.
    Ástvaldsson, Ásgeir
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Pathogenesis and Cell Biology of the Salmon Parasite Spironucleus salmonicida2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Spironucleus species are classified as diplomonad organisms, diverse eukaryotic flagellates found in oxygen-deprived environments. Members of Spironucleus are parasitic and can infect a variety of hosts, such as mice and birds, while the majority are found to infect fish. Massive outbreaks of severe systemic infection caused by a Spironucleus member, Spironucleus salmonicida (salmonicida = salmon killer), have been reported in farmed salmonids resulting in large economic impacts for aquaculture.

    In this thesis, the S. salmonicida genome was sequenced and compared to the genome of its diplomonad relative, the mammalian pathogen G. intestinalis (Paper I). Our analyses revealed large genomic differences between the two parasites that collectively suggests that S. salmonicida is more capable of adapting to different environments. As S. salmonicida can infiltrate different host tissues, we provide molecular evidence for how the parasite can tolerate oxygenated environments and suggest oxygen as a potential regulator of virulence factors (Paper III). To further investigate the molecular responses of the parasite and in addition, its host, during infection we set up an interaction system of S. salmonicida and ASK (Atlantic salmon kidney) cells (Paper VI).

    To study the cell biology in S. salmonicida we optimized an enzymatic proximity labeling method using ascorbate peroxidase (APEX) as a reporter for transmission electron microscopy (TEM) (Paper IV). As the system is robust and versatile, we showed the localization and performed ultrastructural characterization of numerous proteins in S. salmonicida and G. intestinalis. We furthermore utilized the APEX system to study the annexin protein family in S. salmonicida (Paper II). Super resolution microscopy and TEM were applied to show that the annexins are mostly associated with cytoskeletal and membranous structures. In addition, we performed phylogenetic analyses concluding that the annexin gene family is expanded in diplomonads.

    We performed experimental infection in Atlantic salmon and derived a potential model for the route of infection (Paper V). The results suggested multiple routes of transmission between hosts for the parasite.

    To conclude, the comprehensive work in this thesis has provided valuable insights into the pathogenesis and cell biology of the highly adaptable diplomonad parasite S. salmonicida.      

    List of papers
    1. 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, 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
    2. Comparative cell biology and evolution of Annexins in Diplomonads
    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
    3. Oxygen induces the expression of invasion and stress response genes in the anaerobic salmon parasite Spironucleus salmonicida
    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
    4. Proximity Staining using Enzymatic Protein Tagging in Diplomonads
    Open this publication in new window or tab >>Proximity Staining using Enzymatic Protein Tagging in Diplomonads
    2019 (English)In: mSphere, E-ISSN 2379-5042, Vol. 4, no 2, article id e00153-19Article in journal (Refereed) Published
    Abstract [en]

    The diplomonads are a group of understudied eukaryotic flagellates whose most prominent member is the human pathogen Giardia intestinalis. Methods commonly used in other eukaryotic model systems often require special optimization in diplomonads due to the highly derived character of their cell biology. We have optimized a proximity labeling protocol using pea ascorbate peroxidase (APEX) as a reporter for transmission electron microscopy (TEM), to enable study of ultrastructural cellular details in diplomonads. Currently available TEM-compatible tags requires light-induced activation (1, 2) or are inactive in many cellular compartments (3) while ascorbate peroxidase has not been shown to have those limitations. Here we have optimized the in vivo activity of two versions of pea ascorbate peroxidase (APXW41F and APEX) using the diplomonad fish parasite Spironucleus salmonicida, a relative of G. intestinalis. We exploited the well-known peroxidase substrates, Amplex UltraRed and 3,3’-diaminobenzidine (DAB), to validate the activity of the two tags and argue that APEX is the most stable version to use in Spironucleus salmonicida. Next, we fused APEX to proteins with established localization to evaluate the activity of APEX in different cellular compartments of the diplomonad cell and used Amplex UltraRed as well as antibodies along with super-resolution microscopy to confirm the protein-APEX localization. The ultrastructural details of protein-APEX fusions were determined by TEM and we observed marker activity in all cellular compartments tested when using the DAB substrate. Finally, we show that the optimized conditions established for S. salmonicida can be used in the related diplomonad G. intestinalis.

    National Category
    Cell Biology
    Identifiers
    urn:nbn:se:uu:diva-379669 (URN)
    Funder
    Swedish Research Council Formas, 2016-00539
    Available from: 2019-03-19 Created: 2019-03-19 Last updated: 2019-03-20
    5. Experimental challenge of Atlantic salmon (Salmo salar) with the diplomonad parasite Spironucleus salmonicida to characterize the infection cycle
    Open this publication in new window or tab >>Experimental challenge of Atlantic salmon (Salmo salar) with the diplomonad parasite Spironucleus salmonicida to characterize the infection cycle
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Experimental infections were performed of Atlantic salmon (Salmo salar) from the Baltic Sea region with the Diplomonad fish parasite Spironucleus salmonicida in order to define the infection cycle, specifically the time-line and putative routes of transmission. An oral infection protocol using axenic parasites was developed, as were new diagnostic tools using PCR and specific antibodies. We also produced firefly luciferase expressing S. salmonicida parasites that could be identified in the infected fish using in vivo and ex vivo imaging. The new tools made it possible to follow the S. salmonicida infection cycle in detail. Three different stages of the infection were identified: one initial intestinal stage, followed by a blood stage and a final tissue stage. Parasites intubated into the intestine attached to the intestinal surface and were identified in the blood after 1-3 weeks. Skin lesions and infections of the muscles, internal organs and eyes were seen 4-10 weeks after initiation of infection. Several morphologically different forms of S. salmonicida cells were detected in ex vivo cell-cultures of biopsies from skin lesions. By this infection trial we have been able to show that S. salmonicida may use several alternative routes of transmission. One alternative is the fecal-oral route, similar to other Diplomonad parasites but the parasites can also be excreted directly into the surrounding water from the mucous layer of the skin or from an ulcerated skin lesion. This information can be used to prevent the transmission of the parasite in fish farms.

    Keywords
    Diplomonads, Spironucleus salmonis, Salmo salar, fish infection, pathology
    National Category
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-378925 (URN)
    Funder
    Swedish Research Council Formas, 2016-00539
    Available from: 2019-03-09 Created: 2019-03-09 Last updated: 2019-03-19
    6. 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
    Show others...
    (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
  • 12972.
    Åberg, Adam
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Could Lithospermum officinale be bird dispersed?: A greenhouse experiment2015Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Common gromwell (Lithospermum officinale) acts as a host plant for the monophagous moth Ethmia dodecea  whose larvae are completely dependent on the leaves. As conservation authorities now want to reinstate the regionally extinct moth to Mälardalen, a stable population of its host plant is a requirement. To facilitate the work of strengthening the presence of gromwell a partnership was therefore initiated between Västmanland County Board and Uppsala University. In this cooperation, I performed two studies. In the first one I examined how water and temperature affect plant germination and how nutrient levels affect early growth. In the second study I investigated whether the germination is influenced by chemical treatment (soaking in acid) and mechanical damage (seeds scratched with sandpaper) on the seeds. I worked with the hypothesis that gromwell is grazed by cows and is therefore dispersed and germinates in the spring. This should mean high water levels combined with high temperatures would produce higher germination. For the second study, it means that the germination rate should be higher in the seeds treated with the acid than in the scratched and control treatments. In the first study, so few seeds germinated that I could not draw any conclusions, but germinations appear to go faster in the combination with high nutrients high temperature and frequent watering. In the second study, the seeds scraped with sandpaper had the highest germination rate. This indicates that gromwell may be dispersed by birds, and I propose sandpaper rubbing as a method to easily increase the germination rates of L. officinale in greenhouses in order to reinforce small populations in the field. 

  • 12973.
    Åberg, Jan
    et al.
    Department of Ecology and Environmental Science, Umeå University.
    Wallin, Marcus B.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Evaluating a fast headspace method for measuring DIC and subsequent calculation of pCO2 in freshwater systems2014In: Inland Waters, ISSN 2044-2041, EISSN 2044-205X, Vol. 4, no 2, p. 157-166Article in journal (Refereed)
    Abstract [en]

    A variety of different sampling and analysis methods are found in the literature for determining carbon dioxide (CO2) in freshwaters, methods that rarely have been evaluated or compared. Here we present an evaluation of an acidified headspace method (AHS) in which the dissolved inorganic carbon (DIC) is measured from an acidified sample and the partial pressure (pCO2) is calculated from DIC using pH and water temperature. We include information on practical sampling, accuracy, and precision of the DIC/pCO2 determination and a storage test of samples. The pCO2 determined from the AHS method is compared to that obtained from the more widely used direct headspace method (DHS) in which CO2 is equilibrated between the water and gas phases at ambient pH. The method was tested under both controlled laboratory conditions as well as wintertime field sampling. The accuracy of the DIC detection was on average 99% based on prepared standard solutions. The pCO2 determination in lab, using the DHS method as a reference, showed no significant difference, although the discrepancy between the methods was larger in samples with <1000 µatm. The precision of the pCO2 determination was on average ±4.3%, which was slightly better than the DHS method (±6.7%). In the field, the AHS method determined on average 10% higher pCO2 than the DHS method, which was explained by the extreme winter conditions (below −20 °C) at sampling that affected the sampling procedure of the DHS method. Although samples were acidified to pH 2, respiration processes were still occurring (at a low rate), and we recommend that analyses are conducted within 3 days from sampling. The AHS method was found to be a robust method to determine DIC and pCO2 in acidic to pH-neutral freshwater systems. The simple and quick sampling procedure makes the method suitable for time-limited sampling campaigns and sampling in cold climate.

  • 12974.
    Åberg, Karolina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Finding Genes for Schizophrenia2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Schizophrenia is one of our most common psychiatric diseases. It severely affects all aspects of psychological functions and results in loss of contact with reality. No cure exists and the treatments available today produce only partial relief for disease symptoms. The aim of this work is to better understand the etiology of schizophrenia by identification of candidate genes and gene pathways involved in the development of the disease.

    In a preliminarily study, the effects of medication and genetic factors were investigated in a candidate gene, serotonin 2C receptor. This study distinguished pharmacological effects, caused by neuroleptics, and/or genetic effects, caused by unique polymorphisms, from other effects responsible for mRNA expression changes on candidate genes.

    The core of the thesis describes a new candidate gene for schizophrenia, the quaking homolog, KH domain RNA binding (mouse) or QKI, located on chromosome 6q26-q27. The identification of QKI is supported by previous linkage studies, current association studies and mRNA expression studies using three different sample sets. The investigated samples included a 12-generation pedigree with 16 distantly related schizophrenic cases and their parents, 176 unrelated nuclear families with at least one affected child in each family and human brain autopsies from 55 schizophrenic cases and from 55 controls. Indirect evidence showing involvement of QKI in myelin regulation of central nervous system is presented. Myelin plays an important role in development of normal brains and disruption of QKI might lead to schizophrenia symptoms.

    In a forth sample set, including extended pedigrees originated from a geographically isolated area above the Arctic Circle, in northeast Sweden, two additional schizophrenia susceptibility loci were identified, 2q13 and 5q21. Both these regions have previously been highlighted as potential schizophrenia loci in several other investigations, including a large Finnish study. This suggests common schizophrenia susceptibility loci for Nordic populations.

    A pilot investigation including a genome wide haplotype analysis is presented. This statistical strategy could be further developed and applied to the artic Swedish families, including analysis of 900 microsatellites and 10,000 SNPs.

    These findings will facilitate the understanding of the schizophrenia etiology and may lead to development of more efficient treatments for patients that suffer from schizophrenia.

    List of papers
    1. Serotonin Receptor 2C (HTR2C) and Schizophrenia: Examination of Possible Medication and Genetic Influences on Expression Levels
    Open this publication in new window or tab >>Serotonin Receptor 2C (HTR2C) and Schizophrenia: Examination of Possible Medication and Genetic Influences on Expression Levels
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    2005 (English)In: American Journal of Medical Genetics, ISSN 0148-7299, E-ISSN 1096-8628, Vol. 134B, p. 84-89Article in journal (Refereed) Published
    Abstract [en]

    The serotonin receptor 2C (HTR2C) gene is of interest in schizophrenia due to its involvement in regulation of dopamine activity in the prefrontal cortex. We have previously reported a decreased expression of HTR2C mRNA levels in the prefrontal cortex of schizophrenia patients. The variability in mRNA expression levels is evaluated here more closely in relation to promoter haplotypes and neuroleptic treatment received by the patients. The decrease in HTR2C mRNA was present in neuroleptic treated individuals and in patients untreated at death, indicating that the lower expression is not a short-term medication effect. Three promoter polymorphisms were used to construct haplotypes. No SNP displayed genotypic or haplotypic association with the disease. Gene expression of HTR2C was not affected by haplotype and the expression decrease in schizophrenia patients was similar in all haplotype combinations (diplotypes). We conclude that the decrease in HTR2C expression in schizophrenia may be related to the disease mechanism rather than to drug treatment. The disease related changes in HTR2C expression are not related to the promoter variants typed in our sample, but could be due to other regulatory variants or trans-acting factors.

    Keywords
    mRNA expression, neuroleptic drugs, psychiatric disease, serotonin receptor 2C, promoter polymorphisms
    National Category
    Genetics
    Identifiers
    urn:nbn:se:uu:diva-93323 (URN)10.1002/ajmg.b.30151 (DOI)15717293 (PubMedID)
    Available from: 2005-09-01 Created: 2005-09-01 Last updated: 2017-12-14Bibliographically approved
    2. Reconstruction of Ancestral Haplotypes in a 12-Generation Schizophrenia Pedigree
    Open this publication in new window or tab >>Reconstruction of Ancestral Haplotypes in a 12-Generation Schizophrenia Pedigree
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    2004 (English)In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 14, no 1, p. 1-8Article in journal (Refereed) Published
    Abstract [en]

    We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 10p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.

    Keywords
    psychiatric genetics, schizophrenia, ancestral haplotypes, susceptibility loci
    National Category
    Genetics
    Identifiers
    urn:nbn:se:uu:diva-93324 (URN)10.1097/01.ypg.0000084941.07075.f9 (DOI)15091309 (PubMedID)
    Available from: 2005-09-01 Created: 2005-09-01 Last updated: 2017-12-14Bibliographically approved
    3. Human QKI, a New Candidate Gene for Schizophrenia Involved in Myelination
    Open this publication in new window or tab >>Human QKI, a New Candidate Gene for Schizophrenia Involved in Myelination
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    2005 (English)In: American journal of medical genetics. Part B, Neuropsychiatric genetics, ISSN 1552-4841, Vol. 141B, no 1, p. 84-90Article in journal (Refereed) Published
    Abstract [en]

    We have previously shown that chromosome 6q25-6q27 includes a susceptibility locus for schizophrenia in a large pedigree from northern Sweden. In this study, we fine-mapped a 10.7 Mb region, included in this locus, using 42 microsatellites or SNP markers. We found a 0.5 Mb haplotype, likely to be inherited identical by decent, within the large family that is shared among the majority of the patients (69%). A gamete competition test of this haplotype in 176 unrelated nuclear families from the same geographical area as the large family showed association to schizophrenia (empirical P-value 0.041). The only gene located in the region, the quaking homolog, KH domain RNA binding (mouse) (QKI), was investigated in human brain autopsies from 55 cases and 55 controls using a high-resolution mRNA expression analysis. Relative mRNA expression levels of two QKI splice variants were clearly downregulated in schizophrenic patients (P-value 0.0004 and 0.03, respectively). The function of QKI has not been studied in humans, but the mouse homolog is involved in neural development and myelination. In conclusion, we present evidence from three unrelated sample-sets that propose the involvement of the QKI gene in schizophrenia. The two family based studies suggest that there may be functional variants of the QKI gene that increase the susceptibility of schizophrenia in northern Sweden, whereas the case-control study suggest that splicing of the gene may be disturbed in schizophrenic patients from other geographical origins. Taken together, we propose QKI as a possible target for functional studies related to the role of myelination in schizophrenia.

    Keywords
    mRNA-expression, haplotype investigation, fine-mapping, large pedigree
    National Category
    Genetics
    Identifiers
    urn:nbn:se:uu:diva-93325 (URN)10.1002/ajmg.b.30243 (DOI)16342280 (PubMedID)