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  • 1. Ahmad, S.
    et al.
    Zhao, W.
    Renström, F.
    Rasheed, A.
    Zaidi, M.
    Samuel, M.
    Shah, N.
    Mallick, N. H.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Zaman, K. S.
    Ishaq, M.
    Rasheed, S. Z.
    Memon, F-ur-R
    Hanif, B.
    Lakhani, M. S.
    Ahmed, F.
    Kazmi, S. U.
    Deloukas, P.
    Frossard, P.
    Franks, P. W.
    Saleheen, D.
    A novel interaction between theFLJ33534locus and smokingin obesity: a genome-wide study of 14 131 Pakistani adults2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 1, p. 186-190Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene-lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome-wide approaches to investigate gene-lifestyle interactions in obesity. METHODS: In the Pakistan Risk of Myocardial Infraction Study, a cross-sectional study based in Pakistan, we calculated body mass index (BMI) variance estimates (square of the residual of inverse-normal transformed BMI z-score) in 14 131 participants and conducted genome-wide heterogeneity of variance analyses (GWHVA) for this outcome. All analyses were adjusted for age, age(2), sex and genetic ancestry. RESULTS: The GWHVA analyses identified an intronic variant, rs140133294, in the FLJ33544 gene in association with BMI variance (P-value = 3.1 x 10(-8)). In explicit tests of gene x lifestyle interaction, smoking was found to significantly modify the effect of rs140133294 on BMI (Pinteraction = 0.0005), whereby the minor allele (T) was associated with lower BMI in current smokers, while positively associated with BMI in never smokers. Analyses of ENCODE data at the FLJ33534 locus revealed features indicative of open chromatin and high confidence DNA-binding motifs for several transcription factors, providing suggestive biological support for a mechanism of interaction. CONCLUSIONS: In summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.

  • 2. Ausin, Israel
    et al.
    Feng, Suhua
    Yu, Chaowei
    Liu, Wanlu
    Kuo, Hsuan Yu
    Jacobsen, Elise L.
    Zhai, Jixian
    Gallego-Bartolome, Javier
    Wang, Lin
    Egertsdotter, Ulrika
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jacobsen, Steven E.
    Wang, Haifeng
    DNA methylome of the 20-gigabase Norway spruce genome2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 50, p. E8106-E8113Article in journal (Refereed)
    Abstract [en]

    DNA methylation plays important roles in many biological processes, such as silencing of transposable elements, imprinting, and regulating gene expression. Many studies of DNA methylation have shown its essential roles in angiosperms (flowering plants). However, few studies have examined the roles and patterns of DNA methylation in gymnosperms. Here, we present genome-wide high coverage single-base resolution methylation maps of Norway spruce (Picea abies) from both needles and somatic embryogenesis culture cells via whole genome bisulfite sequencing. On average, DNA methylation levels of CG and CHG of Norway spruce were higher than most other plants studied. CHH methylation was found at a relatively low level; however, at least one copy of most of the RNA-directed DNA methylation pathway genes was found in Norway spruce, and CHH methylation was correlated with levels of siRNAs. In comparison with needles, somatic embryogenesis culture cells that are used for clonally propagating spruce trees showed lower levels of CG and CHG methylation but higher level of CHH methylation, suggesting that like in other species, these culture cells show abnormal methylation patterns.

  • 3. Bailey-Wilson, Joan E
    et al.
    Childs, Erica J
    Cropp, Cheryl D
    Schaid, Daniel J
    Xu, Jianfeng
    Camp, Nicola J
    Cannon-Albright, Lisa A
    Farnham, James M
    George, Asha
    Powell, Isaac
    Carpten, John D
    Giles, Graham G
    Hopper, John L
    Severi, Gianluca
    English, Dallas R
    Foulkes, William D
    Maehle, Lovise
    Moller, Pal
    Eeles, Rosalind
    Easton, Douglas
    Guy, Michelle
    Edwards, Steve
    Badzioch, Michael D
    Whittemore, Alice S
    Oakley-Girvan, Ingrid
    Hsieh, Chih-Lin
    Dimitrov, Latchezar
    Stanford, Janet L
    Karyadi, Danielle M
    Deutsch, Kerry
    McIntosh, Laura
    Ostrander, Elaine A
    Wiley, Kathleen E
    Isaacs, Sarah D
    Walsh, Patrick C
    Thibodeau, Stephen N
    McDonnell, Shannon K
    Hebbring, Scott
    Lange, Ethan M
    Cooney, Kathleen A
    Tammela, Teuvo LJ
    Schleutker, Johanna
    Maier, Christiane
    Bochum, Sylvia
    Hoegel, Josef
    Gronberg, Henrik
    Wiklund, Fredrik
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cancel-Tassin, Geraldine
    Valeri, Antoine
    Cussenot, Olivier
    Isaacs, William B
    Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families2012In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, p. 46-Article in journal (Refereed)
    Abstract [en]

    Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.

    Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.

    Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.

    Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

  • 4.
    Beier, Frank
    et al.
    Institut für Experimentelle Medizin, Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Medical Biochemistry, University of Calgary, Calgary, Canada.
    Vornehm, Silvia
    Institut für Experimentelle Medizin, Universität Erlangen-Nürnberg, Erlangen, Germany.
    Pöschl, Ernst
    Institut für Experimentelle Medizin, Universität Erlangen-Nürnberg, Erlangen, Germany.
    von der Mark, Klaus
    Institut für Experimentelle Medizin, Universität Erlangen-Nürnberg, Erlangen, Germany.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Localization of silencer and enhancer elements in the human type X collagen gene.1997In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 66, no 2, p. 210-218, article id 9213222Article in journal (Refereed)
    Abstract [en]

    Collagen type X is a short, network-forming collagen expressed temporally and spatially tightly controlled in hypertrophic chondrocytes during endochondral ossification. Studies on chicken chondrocytes indicate that the regulation of type X collagen gene expression is regulated at the transcriptional level. In this study, we have analyzed the regulatory elements of the human type X collagen (Col10a1) by reporter gene constructs and transient transfections in chondrogenic and nonchondrogenic cells. Four different promoter fragments covering up to 2,864 bp of 5'-flanking sequences, either including or lacking the first intron, were linked to luciferase reporter gene and transfected into 3T3 fibroblasts, HT1080 fibrosarcoma cells, prehypertrophic chondrocytes from the resting zone, hypertrophic chondrocytes, and chondrogenic cell lines. The results indicated the presence of three regulatory elements in the human Col10a1 gene besides the proximal promoter. First, a negative regulatory element located between 2.4 and 2.8 kb upstream of the transcription initiation site was active in all nonchondrogenic cells and in prehypertrophic chondrocytes. Second, a positive, but also non-tissue-specific positive regulatory element was present in the first intron. Third, a cell-type-specific enhancer element active only in hypertrophic chondrocytes was located between -2.4 and -0.9 kb confirming a previous report by Thomas et al. [(1995): Gene 160:291-296]. The enhancing effect, however, was observed only when calcium phosphate was either used for transfection or included in the culture medium after lipofection. These findings demonstrate that the rigid control of human Col10a1 gene expression is achieved by both positive and negative regulatory elements in the gene and provide the basis for the identification of factors binding to those elements.

  • 5.
    Benedict, Catherine
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Skinner, J. S.
    Meng, R.
    Chang, Y.
    Bhalerao, R.
    Finn, C.
    Chen, T. H. H.
    Umeå University, Faculty of Science and Technology.
    Hurry, Vaughan
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    The Role of the CBF-dependent Signalling Pathway in Woody Perennials2006In: Cold Hardiness in Plants: Molecular Genetics, Cell Biology and Physiology / [ed] T Chen, M Uemura, S Fujikawa, Wallingford: CABI Publishing, 2006, p. 167-180Chapter in book (Other academic)
  • 6.
    Bernhardsson, Carolina
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Molecular population genetics of inducible defense genes in Populus tremula2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Plant-herbivore interactions are among the most common of ecological interactions. It is therefore not surprising that plants have evolved multiple mechanisms to defend themselves, using both constitutive chemical and physical barriers and by induced responses which are only expressed after herbivory has occurred. Herbivores, on the other hand, respond to these plant defenses by evolving counter-adaptations which makes defenses less effective or even useless. Adaptation can occur at different geographical scales, with varying coevolutionary interactions across a spatially heterogenous landscape. By looking at the underlying genes responsible for these defensive traits and herbivore related phenotypic traits, it is possible to investigate the coevolutionary history of these plant- herbivore interactions. Here I use molecular population genetic tools to investigate the evolutionary history of several inducible defense genes in European Aspen (Populus tremula) in Sweden. Two genes, belonging to the Polyphenol oxidase gene-family (PPO1 and PPO2), show skews in their site frequency spectrum together with patterns of diversity and divergence from an outgroup which correspond to signatures of adaptive evolution (Paper II). 71 single nucleotide polymorphisms (SNPs) from seven inducible defense genes (PPO1-PPO3, TI2-TI5) show elevated levels of population differentiation compared to control genes (genes not involved in plant defense), and 10 of these defense SNPs show strong signatures of natural selection (Paper III). These 71 defense SNPs also divides a sample of Swedish P. tremula trees into three distinct geographical groups, corresponding to a Southern, Central and Northern cluster, a patterns that is not present in control SNPs (Paper III). The same geographical pattern, with a distinct Northern cluster, is also observed in several phenotypic traits related to herbivory in our common garden in Sävar (Paper IV). These phenotypic traits show patterns of apparent local maladaptation of the herbivore community to the host population which could indicate the presence of “information coevolution” between plants and herbivores (Paper IV). 15 unique defense SNPs also show significant associations to eight phenotypic traits but the causal effects of these SNP associations may be confounded by the geographic structure found in both the underlying genes and in the phenotypic traits. The co-occurrence of population structure in both defense genes and herbivore community traits may be the result from historical events during the post-glacial recolonization of Sweden.

  • 7.
    Bernhardsson, Carolina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Ingvarsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Geographic structure and adaptive population differentiation in herbivore defence genes in European aspen (Populus tremula L., Salicaceae)2012In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 21, no 9, p. 2197-2207Article in journal (Refereed)
    Abstract [en]

    When a phenotypic trait is subjected to spatially variable selection and local adaptation, the underlying genes controlling the trait are also expected to show strong patterns of genetic differentiation since alternative alleles are favored in different geographical locations. Here we study 71 SNPs from seven genes associated with inducible defense responses in a sample of P. tremula collected from across Sweden. Four of these genes (PPO2, TI2, TI4 and TI5) show substantial population differentiation and a PCA conducted on the defense SNPs divides the Swedish population into three distinct clusters. Several defense SNPs show latitudinal clines, although these were not robust to multiple testing. However, five SNPs (located within TI4 and TI5) show strong longitudinal clines that remain significant after multiple test correction. Genetic geographical variation, supporting local adaptation, has earlier been confirmed in genes involved in the photoperiod pathway in P. tremula, but this is, to our knowledge, one of the first times that geographic variation has been found in genes involved in plant defense against antagonists.

  • 8.
    Bernhardsson, Carolina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Robinson, Kathryn M.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Abreu, Ilka N.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Albrectsen, Benedicte R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Population differentiation in arthropod community structure and phenotypic association with inducible defense genes in European Aspen (Populus tremula L., salicaceae)Manuscript (preprint) (Other academic)
    Abstract [en]

    Plant-herbivore interactions are known to vary across a landscape due to both variation in abiotic and biotic factors. Such spatial variation tends to promoting local adaption of plants to the prevailing herbivore regime. Here we use data from a common garden to look for patterns across populations in the abundance and diversity of herbivorous insects. We also screen for variation in the untargeted metabolome of the foliage of a subset of the same trees. We also search for phenotypic associations between genetic variation in a number of wound-induced genes and phenotypic variation in herbivore abundance, diversity and in metabolomes. We observe significant genetic variation in a number of herbivore-related traits but low correlations between traits. We do observe substantial genetic structure in both herbivore community structure and in metabolic profiles and this structure is aligned with genetic structure we have previously documented for a set of defense genes. We also identify a number of significant associations between SNPs from wound-induced defense genes and a number of the herbivore traits and metabolic profiles. However, these associations are likely not causal, but are rather caused by the underlying population structure we observe. These results highlight to the importance of historical processes and the need to better understand both the current-day geographic distribution of different herbivore species as well as the post-glacial colonization history of both plants and herbivores.

  • 9. Bochman, Matthew L
    et al.
    Sabouri, Nasim
    Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA .
    Zakian, Virginia A
    Unwinding the functions of the Pif1 family helicases2010In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 9, no 3, p. 237-249Article in journal (Refereed)
    Abstract [en]

    Helicases are ubiquitous enzymes found in all organisms that are necessary for all (or virtually all) aspects of nucleic acid metabolism. The Pif1 helicase family is a group of 5'-->3' directed, ATP-dependent, super family IB helicases found in nearly all eukaryotes. Here, we review the discovery, evolution, and what is currently known about these enzymes in Saccharomyces cerevisiae (ScPif1 and ScRrm3), Schizosaccharomyces pombe (SpPfh1), Trypanosoma brucei (TbPIF1, 2, 5, and 8), mice (mPif1), and humans (hPif1). Pif1 helicases variously affect telomeric, ribosomal, and mitochondrial DNA replication, as well as Okazaki fragment maturation, and in at least some cases affect these processes by using their helicase activity to disrupt stable nucleoprotein complexes. While the functions of these enzymes vary within and between organisms, it is evident that Pif1 family helicases are crucial for both nuclear and mitochondrial genome maintenance.

  • 10.
    Boija, Ann
    et al.
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden.
    Holmqvist, Per-Henrik
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden.
    Philip, Philge
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Computational Life Science Cluster (CLiC), Umeå, Sweden.
    Zare, Aman
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Computational Life Science Cluster (CLiC), Umeå, Sweden.
    Meyers, David J.
    Dept. Pharmacology and Molecular Sciences, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
    Cole, Philip A.
    Dept. Pharmacology and Molecular Sciences, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Division of CBRN Defence and Security, FOI, Swedish Defence Research Agency, Sweden.
    Mannervik, Mattias
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, SwedenDept. Pharmacology and Molecular Sciences, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
    Drosophila CBP cooperates with GAGA factor to induce high levels of Pol II promoter-proximal pausingManuscript (preprint) (Other academic)
  • 11. Bosley, Katrine S
    et al.
    Botchan, Michael
    Bredenoord, Annelien L
    Carroll, Dana
    Charo, R Alta
    Charpentier, Emmanuelle
    Cohen, Ron
    Corn, Jacob
    Doudna, Jennifer
    Feng, Guoping
    Greely, Henry T
    Isasi, Rosario
    Ji, Weihzi
    Kim, Jin-Soo
    Knoppers, Bartha
    Lanphier, Edward
    Li, Jinsong
    Lovell-Badge, Robin
    Martin, G Steven
    Moreno, Jonathan
    Naldini, Luigi
    Pera, Martin
    Perry, Anthony C F
    Venter, J Craig
    Zhang, Feng
    Zhou, Qi
    CRISPR germline engineering: the community speaks2015In: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 33, no 5, p. 478-486Article in journal (Refereed)
  • 12. Brown, Keith S., Jr.
    et al.
    von Schoultz, Barbara
    Saura, Anja O.
    Saura, Anssi
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Chromosomal evolution in the South American Riodinidae (Lepidoptera Papilionoidea)2012In: Hereditas, ISSN 0018-0661, E-ISSN 1601-5223, Vol. 149, no 4, p. 128-138Article in journal (Refereed)
    Abstract [en]

    We give the haploid chromosome numbers of 173 species or subspecies of Riodinidae as well as of 17 species or subspecies of neotropical Lycaenidae for comparison. The chromosome numbers of riodinids have thus far been very poorly known. We find that their range of variation extends from n =?9 to n =?110 but numbers above n =?31 are rare. While lepidopterans in general have stable chromosome numbers, or variation is limited at most a subfamily or genus, the entire family Riodinidae shows variation within genera, tribes and subfamilies with no single modal number. In particular, a stepwise pattern with chromosome numbers that are about even multiples is seen in several unrelated genera. We propose that this variation is attributable to the small population sizes, fragmented populations with little migration, and the behavior of these butterflies. Small and isolated riodinid populations would allow for inbreeding to take place. Newly arisen chromosomal variants could become fixed and contribute to reproductive isolation and speciation. In contrast to the riodinids, the neotropical Lycaenidae (Theclinae and Polyommatinae) conform to the modal n =?24 that characterizes the family.

  • 13.
    Buckland, Philip I.
    et al.
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies, Environmental Archaeology Lab.
    Hammarlund, Dan
    Lund University.
    Hjärthner-Holdar, Eva
    Swedish National Historical Museums.
    Lidén, Kerstin
    Stockholm University.
    Lindahl, Anders
    Lund University.
    Palm, Fredrik
    Umeå University, Faculty of Arts, Humlab.
    Possnert, Göran
    Uppsala University.
    The Strategic Environmental Archaeology Database: a resource for international, multiproxy and transdisciplinary studies of environmental and climatic change2015Conference paper (Refereed)
    Abstract [en]

    Climate and environmental change are global challenges which require global data and infrastructure to investigate. These challenges also require a multi-proxy approach, integrating evidence from Quaternary science and archaeology with information from studies on modern ecology and physical processes among other disciplines. The Strategic Environmental Archaeology Database (SEAD http://www.sead.se) is a Swedish based international research e-infrastructure for storing, managing, analysing and disseminating palaeoenvironmental data from an almost unlimited number of analysis methods. The system currently makes available raw data from over 1500 sites (>5300 datasets) and the analysis of Quaternary fossil insects, plant macrofossils, pollen, geochemistry and sediment physical properties, dendrochronology and wood anatomy, ceramic geochemistry and bones, along with numerous dating methods. This capacity will be expanded in the near future to include isotopes, multi-spectral and archaeo-metalurgical data. SEAD also includes expandable climate and environment calibration datasets, a complete bibliography and extensive metadata and services for linking these data to other resources. All data is available as Open Access through http://qsead.sead.se and downloadable software.

     

    SEAD is maintained and managed at the Environmental Archaeology Lab and HUMlab at Umea University, Sweden. Development and data ingestion is progressing in cooperation with The Laboratory for Ceramic Research and the National Laboratory for Wood Anatomy and Dendrochronology at Lund University, Sweden, the Archaeological Research Laboratory, Stockholm University, the Geoarchaeological Laboratory, Swedish National Historical Museums Agency and several international partners and research projects. Current plans include expanding its capacity to serve as a data source for any system and integration with the Swedish National Heritage Board's information systems.

     

    SEAD is partnered with the Neotoma palaeoecology database (http://www.neotomadb.org) and a new initiative for building cyberinfrastructure for transdisciplinary research and visualization of the long-term human ecodynamics of the North Atlantic funded by the National Science Foundation (NSF).

  • 14. Bykova, Natalia V.
    et al.
    Møller, Ian M.
    Gardeström, Per
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Igamberdiev, Abir U.
    The function of glycine decarboxylase complex is optimized to maintain high photorespiratory flux via buffering of its reaction products2014In: Mitochondrion (Amsterdam. Print), ISSN 1567-7249, E-ISSN 1872-8278, Vol. 19, p. 357-364Article in journal (Refereed)
    Abstract [en]

    Oxidation of glycine in photorespiratory pathway is the major flux through mitochondria of C3 plants in the light. It sustains increased intramitochondrial concentrations of NADH and NADPH, which are required to engage the internal rotenone-insensitive NAD(P)H dehydrogenases and the alternative oxidase. We discuss here possible mechanisms of high photorespiratory flux maintenance in mitochondria and suggest that it is fulfilled under conditions where the concentrations of glycine decarboxylase reaction products NADH and CO2 achieve an equilibrium provided by malate dehydrogenase and carbonic anhydrase, respectively. This results in the removal of these products from the glycine decarboxylase multienzyme active sites and in the maintenance of their concentrations at levels sufficiently low to prevent substrate inhibition of the reaction. 

  • 15. Castelain, Mathieu
    et al.
    Le Hir, Rozenn
    Bellini, Catherine
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    The non-DNA-binding bHLH transcription factor PRE3/bHLH135/ATBS1/TMO7 is involved in the regulation of light signaling pathway in Arabidopsis2012In: Physiologia Plantarum: An International Journal for Plant Biology, ISSN 0031-9317, E-ISSN 1399-3054, Vol. 145, no 3, p. 450-460Article in journal (Refereed)
    Abstract [en]

    Plant basic Helix-loop-helix (bHLH) proteins are transcription factors that are involved in many developmental mechanisms, including light signaling and hormone homeostasis. Some of them are non-DNA-binding proteins and could act as dominant negative regulators of other bHLH proteins by forming heterodimers, in a similar way to animal inhibitor of DNA-binding proteins. It has been recently reported that several non-DNA-binding bHLHs are involved in light signaling (KDR/PRE6), gibberellic acid signaling (PRE1/BNQ1/bHLH136) or brassinosteroid signaling (ATBS1). Here we report that Arabidopsis lines overexpressing the PRE3/bHLH135/ATBS1/TMO7 gene are less responsive to red, far-red and blue light than wild-type which is likely to explain the light hyposensitive phenotype displayed when grown under white light conditions. Using quantitative polymerase chain reaction, we show that the expression of PRE3 and KDR/PRE6 genes is regulated by light and that light-related genes are deregulated in the PRE3-ox lines. We show that PRE3 is expressed in the shoot and root meristems and that PRE3-ox lines also have a defect in lateral root development. Our results not only suggest that PRE3 is involved in the regulation of light signaling, but also support the hypothesis that non-DNA-binding bHLH genes are promiscuous genes regulating a wide range of both overlapping and specific regulatory pathways.

  • 16.
    Charpentier, Emmanuelle
    et al.
    Department of Regulation in Infection Biology, Max Planck Institute for Infection Biology.
    Hess, Wolfgang R
    RNA in bacteria: biogenesis, regulatory mechanisms and functions2015In: FEMS Microbiology Reviews, ISSN 0168-6445, E-ISSN 1574-6976, Vol. 39, no 3, p. 277-279Article in journal (Refereed)
  • 17.
    Chen, Changchun
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Huang, Bo
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Anderson, James T
    Byström, Anders S
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Unexpected accumulation of ncm5U and ncm5s2U in a trm9 mutant suggests an additional step in the synthesis of mcm5U and mcm5s2U.2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, p. e20783-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Transfer RNAs are synthesized as a primary transcript that is processed to produce a mature tRNA. As part of the maturation process, a subset of the nucleosides are modified. Modifications in the anticodon region often modulate the decoding ability of the tRNA. At position 34, the majority of yeast cytosolic tRNA species that have a uridine are modified to 5-carbamoylmethyluridine (ncm(5)U), 5-carbamoylmethyl-2'-O-methyluridine (ncm(5)Um), 5-methoxycarbonylmethyl-uridine (mcm(5)U) or 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U). The formation of mcm(5) and ncm(5) side chains involves a complex pathway, where the last step in formation of mcm(5) is a methyl esterification of cm(5) dependent on the Trm9 and Trm112 proteins.

    METHODOLOGY AND PRINCIPAL FINDINGS: Both Trm9 and Trm112 are required for the last step in formation of mcm(5) side chains at wobble uridines. By co-expressing a histidine-tagged Trm9p together with a native Trm112p in E. coli, these two proteins purified as a complex. The presence of Trm112p dramatically improves the methyltransferase activity of Trm9p in vitro. Single tRNA species that normally contain mcm(5)U or mcm(5)s(2)U nucleosides were isolated from trm9Δ or trm112Δ mutants and the presence of modified nucleosides was analyzed by HPLC. In both mutants, mcm(5)U and mcm(5)s(2)U nucleosides are absent in tRNAs and the major intermediates accumulating were ncm(5)U and ncm(5)s(2)U, not the expected cm(5)U and cm(5)s(2)U.

    CONCLUSIONS: Trm9p and Trm112p function together at the final step in formation of mcm(5)U in tRNA by using the intermediate cm(5)U as a substrate. In tRNA isolated from trm9Δ and trm112Δ strains, ncm(5)U and ncm(5)s(2)U nucleosides accumulate, questioning the order of nucleoside intermediate formation of the mcm(5) side chain. We propose two alternative explanations for this observation. One is that the intermediate cm(5)U is generated from ncm(5)U by a yet unknown mechanism and the other is that cm(5)U is formed before ncm(5)U and mcm(5)U.

  • 18.
    Chen, Changchun
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Huang, Bo
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Eliasson, Mattias
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Byström, Anders S
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification2011In: PLoS genetics, ISSN 1553-7404, Vol. 7, no 9, p. e1002258-Article in journal (Refereed)
    Abstract [en]

    Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm(5)U(34)), 5-methoxycarbonylmethyluridine (mcm(5)U(34)), and 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation. In a recent publication, Elongator complex was implicated to participate in telomeric gene silencing and DNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of tRNA(Lys) (s(2) ) (UUU), tRNA(Gln) (s(2) ) (UUG), and tRNA(Glu) (s(2) ) (UUC), which in a wild-type background contain the mcm(5)s(2)U nucleoside at position 34, suppress the defects in telomeric gene silencing and DNA damage response observed in the Elongator mutants. We also found that the reported differences in telomeric gene silencing and DNA damage response of various elp3 alleles correlated with the levels of modified nucleosides at U(34). Defects in telomeric gene silencing and DNA damage response are also observed in strains with the tuc2Δ mutation, which abolish the formation of the 2-thio group of the mcm(5)s(2)U nucleoside in tRNA(Lys) (mcm(5) (s(2) ) (UUU) ), tRNA(Gln) (mcm(5) (s(2) ) (UUG) ), and tRNA(Glu) (mcm(5) (s(2) ) (UUC) ). These observations show that Elongator complex does not directly participate in telomeric gene silencing and DNA damage response, but rather that modified nucleosides at U(34) are important for efficient expression of gene products involved in these processes. Consistent with this notion, we found that expression of Sir4, a silent information regulator required for assembly of silent chromatin at telomeres, was decreased in the elp3Δ mutants.

  • 19. Chen, Peng
    et al.
    Jäger, Gunilla
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Zheng, Bo
    Transfer RNA modifications and genes for modifying enzymes in Arabidopsis thaliana2010In: BMC Plant Biology, ISSN 1471-2229, E-ISSN 1471-2229, Vol. 10, article id 201Article in journal (Refereed)
    Abstract [en]

    Background: In all domains of life, transfer RNA (tRNA) molecules contain modified nucleosides. Modifications to tRNAs affect their coding capacity and influence codon-anticodon interactions. Nucleoside modification deficiencies have a diverse range of effects, from decreased virulence in bacteria, neural system disease in human, and gene expression and stress response changes in plants. The purpose of this study was to identify genes involved in tRNA modification in the model plant Arabidopsis thaliana, to understand the function of nucleoside modifications in plant growth and development. Results: In this study, we established a method for analyzing modified nucleosides in tRNAs from the model plant species, Arabidopsis thaliana and hybrid aspen (Populus tremula x tremuloides). 21 modified nucleosides in tRNAs were identified in both species. To identify the genes responsible for the plant tRNA modifications, we performed global analysis of the Arabidopsis genome for candidate genes. Based on the conserved domains of homologs in Sacccharomyces cerevisiae and Escherichia coli, more than 90 genes were predicted to encode tRNA modifying enzymes in the Arabidopsis genome. Transcript accumulation patterns for the genes in Arabidopsis and the phylogenetic distribution of the genes among different plant species were investigated. Transcripts for the majority of the Arabidopsis candidate genes were found to be most abundant in rosette leaves and shoot apices. Whereas most of the tRNA modifying gene families identified in the Arabidopsis genome was found to be present in other plant species, there was a big variation in the number of genes present for each family. Through a loss of function mutagenesis study, we identified five tRNA modification genes (AtTRM10, AtTRM11, AtTRM82, AtKTI12 and AtELP1) responsible for four specific modified nucleosides (m1G, m2G, m7G and ncm5U), respectively (two genes: AtKTI12 and AtELP1 identified for ncm5U modification). The AtTRM11 mutant exhibited an early-flowering phenotype, and the AtELP1 mutant had narrow leaves, reduced root growth, an aberrant silique shape and defects in the generation of secondary shoots. Conclusions: Using a reverse genetics approach, we successfully isolated and identified five tRNA modification genes in Arabidopsis thaliana. We conclude that the method established in this study will facilitate the identification of tRNA modification genes in a wide variety of plant species.

  • 20.
    Chen, Sa
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Expression and function of Suppressor of zeste 12 in Drosophila melanogaster2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The development of animals and plants needs a higher order of regulation of gene expression to maintain proper cell state. The mechanisms that control what, when and where a gene should (or should not) be expressed are essential for correct organism development. The Polycomb group (PcG) is a family of genes responsible for maintaining gene silencing and Suppressor of zeste 12 (Su(z)12) is one of the core components in the PcG. The gene is highly conserved in organisms ranging from plants to humans, however, the specific function is not well known. The main tasks of this thesis was to investigate the function of Su(z)12 and its expression at different stages of Drosophila development.

    In polytene chromosomes of larval salivary glands, Su(z)12 binds to about 90 specific euchromatic sites. The binding along the chromosome arms is mostly in interbands, which are the most DNA de-condensed regions. The binding sites of Su(z)12 in polytene chromosomes correlate precisely with those of the Enhancer-of-zeste (E(z)) protein, indicating that Su(z)12 mainly exists within the Polycomb Repressive Complex 2 (PRC2). However, the binding pattern does not overlap well with Histone 3 lysine 27 tri-methylations (H3K27me3), the specific chromatin mark created by PRC2. The Su(z)12 binding to chromatin is dynamically regulated during mitotic and meiotic cell division. The two different Su(z)12 isoforms: Su(z)12-A and Su(z)12-B (resulting from alternative RNA splicing), have very different expression patterns during development. Functional analyses indicate that they also have different functions he Su(z)12-B form is the main mediator of silencing. Furthermore, a neuron specific localization pattern in larval brain and a giant larval phenotype in transgenic lines reveal a potential function of Su(z)12-A in neuron development.  In some aspects the isoforms seem to be able to substitute for each other.

    The histone methyltransferase activity of PRC2 is due to the E(z) protein. However, Su(z)12 is also necessary for H3K27me3 methylation in vivo, and it is thus a core component of PRC2. Clonal over-expression of Su(z)12 in imaginal wing discs results in an increased H3K27me3 activity, indicating that Su(z)12 is a limiting factor for silencing. When PcG function is lost, target genes normally become de-repressed. The segment polarity gene engrailed, encoding a transcription factor, is a target for PRC2 silencing. However, we found that it was not activated when PRC2 function was deleted. We show that the Ultrabithorax protein, encoded by another PcG target gene, also acts as an inhibitor of engrailed and that de-regulation of this gene causes a continued repression of engrailed. The conclusion is that a gene can have several negative regulators working in parallel and that secondary effects have to be taken into consideration, when analyzing effects of mutants.

    PcG silencing affects very many cellular processes and a large quantity of knowledge is gathered on the overall mechanisms of PcG regulation. However, little is known about how individual genes are silenced and how cells “remember” their fate through cell generations.

  • 21. Chen, Xinyu
    et al.
    Yuan, Huwei
    Hu, Xiange
    Meng, Jingxiang
    Zhou, Xianqing
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. National Engineering Laboratory for Forest Tree Breeding, Key Laboratory of Genetic and Breeding in Forest Trees and Ornamental Plants of Ministry of Education, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, People’s Republic of China.
    Li, Yue
    Variations in electrical impedance and phase angle among seedlings of Pinus densata and parental species in Pinus tabuliformis habitat environment2015In: Journal of Forestry Research, ISSN 1007-662X, E-ISSN 1993-0607, Vol. 26, no 3, p. 777-783Article in journal (Refereed)
    Abstract [en]

    Electrical impedance (EI) and phase angle (PHI) parameters in AC impedance spectroscopy are important electrical parameters in the study of medical pathology. However, little is known about their application in variation and genetic relationship studies of forest trees. In order to test whether impedance parameters could be used in genetic relationship analysis among conifer species, EI and PHI were measured in a seedling experiment test composed of Pinus tabuliformis, Pinus yunnanensis, and Pinus densata in a habitat of Pinus tabuliformis. The results showed that variations in both EI and PHI among species were significant in different electric frequencies, and the EI and PHI values measured in the two populations of P. densata were between the two parental species, P. yunnanensis and P. tabuliformis. These results show that these two impedance parameters could reflect the genetic relationship among pine species. This was the first time using the two AC impedance spectroscopy parameters to test the genetic relationship analysis between tree species, and would be a hopeful novel reference methodology for future studies in evolution and genetic variation of tree species.

  • 22. Collins, Emily
    et al.
    Sullivan, Alexis R.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Gailing, Oliver
    Limited effective gene flow between two interfertile red oak species2015In: Trees, ISSN 0931-1890, E-ISSN 1432-2285, Vol. 29, no 4, p. 1135-1148Article in journal (Refereed)
    Abstract [en]

    Highly elevated differentiation in different life stages between two interfertile oak species at a CONSTANS -like gene suggests a role of this gene in pre-zygotic isolation and adaptive divergence between species. Genome-wide differentiation patterns among oak species suggest that divergent selection can maintain species-specific adaptations and morphological integrity by reducing effective interspecific gene flow. While there is evidence for both pre- and post-zygotic isolation mechanisms in oaks (e.g., differences in flowering time, selection against hybrids), these mechanisms are rarely studied at each life stage from acorns to adult trees within the same forest. To assess the reproductive isolation mechanisms between two ecologically divergent species, we (1) quantified the number of hybrids in different life stages in Quercus rubra and Quercus ellipsoidalis, two interfertile red oaks with different adaptations to drought, and (2) assessed the timing of bud burst in both natural populations and in a seedling common garden trial. The low number of hybrids in all life stages suggested pre-zygotic isolation between species or selection in very early life stages that have not been sampled (e.g., early seed abortion). Significant differences in bud burst were found in two consecutive years between species in a common garden seedling trial but not in natural populations of the same provenance. In addition, we found evidence for divergent selection on several gene loci between species in each life stage. In particular, an SSR repeat located within the coding sequence of a CONSTANS-like gene, a locus involved in the photoperiodic regulation of flowering time and development, showed very high interspecific differentiation between species in all life stages (mean F (ST) = 0.83), compared to the average neutral differentiation of 3.7 %.

  • 23. Cossu, Rosa Maria
    et al.
    Casola, Claudio
    Giacomello, Stefania
    Vidalis, Amaryllis
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Section of Population Epigenetics and Epigenomics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising, Germany.
    Scofield, Douglas G.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Ecology and Genetics: Evolutionary Biology, Uppsala University, Sweden; Uppsala Multidisciplinary Center for Advanced Computational Science, Uppsala University, Sweden.
    Zuccolo, Andrea
    LTR Retrotransposons Show Low Levels of Unequal Recombination and High Rates of Intraelement Gene Conversion in Large Plant Genomes2017In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, no 12, p. 3449-3462Article in journal (Refereed)
    Abstract [en]

    The accumulat on and removal of transposable elements (TEs) is a major driver of genome size evolution in eukaryotes. In plants, long terminal repeat (LTR) retrotransposons (LTR-RTs) represent the majority of TEs and form most of the nuclear DNA in large genomes. Unequal recombination (UR) between LTRs leads to removal of intervening sequence and formation of solo-LTRs. UR is a major mechanism of LTR-RT removal in many angiosperms, but our understanding of LTR-RT-associated recombination within the large, LTR-RT-rich genomes of conifers is quite limited. We employ a novel read based methodology to estimate the relative rates of LTR-RT-associated UR within the genomes of four conifer and seven angiosperm species. We found the lowest rates of UR in the largest genomes studied, conifers and the angiosperm maize. Recombination may also resolve as gene conversion, which does not remove sequence, so we analyzed LTR-RT-associated gene conversion events (GCEs) in Norway spruce and six angiosperms. Opposite the trend for UR, we found the highest rates of GCEs in Norway spruce and maize. Unlike previous work in angiosperms, we found no evidence that rates of UR correlate with retroelement structural features in the conifers, suggesting that another process is suppressing UR in these species. Recent results from diverse eukaryotes indicate that heterochromatin affects the resolution of recombination, by favoring gene conversion over crossing-over, similar to our observation of opposed rates of UR and GCEs. Control of LTR-RT proliferation via formation of heterochromatin would be a likely step toward large genomes in eukaryotes carrying high LTR-RT content.

  • 24.
    Crona, Filip
    et al.
    Stockholm University, Wenner-Gren Institute, Developmental Biology, Arrhenius laboratories E3, Stockholm SE-10691, Sweden.
    Dahlberg, Olle
    Stockholm University, Wenner-Gren Institute, Developmental Biology, Arrhenius laboratories E3, Stockholm SE-10691, Sweden.
    Lundberg, Lina E
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Mannervik, Mattias
    Stockholm University, Wenner-Gren Institute, Developmental Biology, Arrhenius laboratories E3, Stockholm SE-10691, Sweden.
    Gene regulation by the lysine demethylase KDM4A in Drosophila2013In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 737, no 2, p. 453-463Article in journal (Refereed)
    Abstract [en]

    Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage. KDM4A demethylates H3K36me3, a modification enriched in the 3' end of active genes. The genomic targets and the role of KDM4 proteins in development remain largely unknown. We therefore generated KDM4A mutant Drosophila, and identified 99 mis-regulated genes in first instar larvae. Around half of these genes were down-regulated and the other half up-regulated in dKDM4A mutants. Although heterochromatin protein 1a (HP1a) can stimulate dKDM4A demethylase activity in vitro, we find that they antagonize each other in control of dKDM4A-regulated genes. Appropriate expression levels for some dKDM4A-regulated genes rely on the demethylase activity of dKDM4A, whereas others do not. Surprisingly, although highly expressed, many demethylase-dependent and independent genes are devoid of H3K36me3 in wild-type as well as in dKDM4A mutant larvae, suggesting that some of the most strongly affected genes in dKDM4A mutant animals are not regulated by H3K36 methylation. By contrast, dKDM4A over-expression results in a global decrease in H3K36me3 levels and male lethality, which might be caused by impaired dosage compensation. Our results show that a modest increase in global H3K36me3 levels is compatible with viability, fertility, and the expression of most genes, whereas decreased H3K36me3 levels are detrimental in males.

  • 25.
    Dahlberg, Helena
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Has modern Swedish forestry affected genetic diversity in Norway spruce stands?2015Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Norway spruce is one of two dominating species in Swedish forestry and the most economically important tree species in Sweden. In order to preserve the ability to adapt to a changing environment and to keep populations healthy, genetic diversity has to be preserved. When choosing a small number of individuals from a natural stand to establish a seed orchard the population size decrease. With only a small number of genetically different individuals the risk of inbreeding increase. Furthermore if many clones of the same tree are used in one seed orchard there is also an increased risk selfing. The aim of this study was therefore to investigate whether genetic diversity in Norway spruce differs between age groups and if this can be attributed to forestry practices. All sampling was done from a single location in Västerbotten, Sweden and the different age groups were chosen to represent stands not affected by the modern forest industry to recently planted forests. The chosen age groups are young (12-18 years), intermediate (30-45 years), and old (above 85 years). From each age group 150 individuals were sampled. With genomic microsatellite markers each individual was genotyped at eight simple sequence repeat (SSR) loci. Results show an overall high genetic diversity with an average expected heterozygosity (He) at 0.842 and low genetic differentiation with an average fixation index among populations (FST) of 0.003. The genetic diversity of each age group was also high (He 0.832 to 0.843) and the inbreeding coefficient ranged from 0.061 in the old group to 0.078 in the intermediate group. The pairwise FST value was highest between the old group and the young group but the differentiation was only 0.005 (P=0.001). An analysis of molecular variance also showed that only 0.34% of the total genetic variance was explained by differences among age groups. This study found little evidence for a decrease in genetic diversity due to forestry practices and revealed high genetic diversity and low differentiation between the age groups, indicating a healthy population.

  • 26.
    Davoine, Celine
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Abreu, Ilka N.
    Khajeh, Khalil
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Blomberg, Jeanette
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kidd, Brendan N.
    Kazan, Kemal
    Schenk, Peer M.
    Gerber, Lorenz
    Nilsson, Ove
    Moritz, Thomas
    Björklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Functional metabolomics as a tool to analyze Mediator function and structure in plants2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0179640Article in journal (Refereed)
    Abstract [en]

    Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast. Based on these results, we suggest localization of previously unassigned plant Mediator subunits to specific modules. We also describe novel roles for individual subunits in development, and demonstrate changes in gene expression patterns and specific metabolite levels in med18 and med25, which can explain their phenotypes. We find that med18 displays levels of phytoalexins normally found in wild type plants only after exposure to pathogens. Our results indicate that different Mediator subunits are involved in specific signaling pathways that control developmental processes and tolerance to pathogen infections.

  • 27.
    de La Torre, Amanda R
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Birol, Inanc
    Bousquet, Jean
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jones, Steven J. M
    Keeling, Christopher I
    MacKay, John
    Nilsson, Ove
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Ritland, Kermit
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Yanchuk, Alvin
    Zerbe, Philipp
    Bohlmann, Jörg
    Insights into conifer giga-genomes2014In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 166, no 4, p. 1724-1732Article in journal (Refereed)
    Abstract [en]

    Insights from sequenced genomes of major land plant lineages have advanced research in almost every aspect of plant biology. Until recently, however, assembled genome sequences of gymnosperms have been missing from this picture. Conifers of the pine family (Pinaceae) are a group of gymnosperms that dominate large parts of the world's forests. Despite their ecological and economic importance, conifers seemed long out of reach for complete genome sequencing, due in part to their enormous genome size (20-30 Gb) and the highly repetitive nature of their genomes. Technological advances in genome sequencing and assembly enabled the recent publication of three conifer genomes: white spruce (Picea glauca), Norway spruce (Picea abies), and loblolly pine (Pinus taeda). These genome sequences revealed distinctive features compared with other plant genomes and may represent a window into the past of seed plant genomes. This Update highlights recent advances, remaining challenges, and opportunities in light of the publication of the first conifer and gymnosperm genomes.

  • 28.
    de La Torre, Amanda R.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Sciences, University of California–Davis, Davis, CA.
    Li, Zhen
    Van de Peer, Yves
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Biology, Uppsala Biocenter, Swedish University of Agr icultural Sciences, Uppsala, Sweden.
    Contrasting Rates of Molecular Evolution and Patterns of Selection among Gymnosperms and Flowering Plants2017In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 6, p. 1363-1377Article in journal (Refereed)
    Abstract [en]

    The majority of variation in rates of molecular evolution among seed plants remains both unexplored and unexplained. Although some attention has been given to flowering plants, reports of molecular evolutionary rates for their sister plant clade (gymnosperms) are scarce, and to our knowledge differences in molecular evolution among seed plant clades have never been tested in a phylogenetic framework. Angiosperms and gymnosperms differ in a number of features, of which contrasting reproductive biology, life spans, and population sizes are the most prominent. The highly conserved morphology of gymnosperms evidenced by similarity of extant species to fossil records and the high levels of macrosynteny at the genomic level have led scientists to believe that gymnosperms are slow-evolving plants, although some studies have offered contradictory results. Here, we used 31,968 nucleotide sites obtained from orthologous genes across a wide taxonomic sampling that includes representatives of most conifers, cycads, ginkgo, and many angiosperms with a sequenced genome. Our results suggest that angiosperms and gymnosperms differ considerably in their rates of molecular evolution per unit time, with gymnosperm rates being, on average, seven times lower than angiosperm species. Longer generation times and larger genome sizes are some of the factors explaining the slow rates of molecular evolution found in gymnosperms. In contrast to their slow rates of molecular evolution, gymnosperms possess higher substitution rate ratios than angiosperm taxa. Finally, our study suggests stronger and more efficient purifying and diversifying selection in gymnosperm than in angiosperm species, probably in relation to larger effective population sizes.

  • 29.
    De La Torre, Amanda R
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Lin, Yao-Cheng
    Van de Peer, Yves
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Genome-wide analysis reveals diverged patterns of codon bias, gene expression, and rates of sequence evolution in Picea gene families2015In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 7, no 4, p. 1002-1015Article in journal (Refereed)
    Abstract [en]

    The recent sequencing of several gymnosperm genomes has greatly facilitated studying the evolution of their genes and gene families. In this study, we examine the evidence for expression-mediated selection in the first two fully sequenced representatives of the gymnosperm plant clade (Picea abies and Picea glauca). We use genome-wide estimates of gene expression (> 50,000 expressed genes) to study the relationship between gene expression, codon bias, rates of sequence divergence, protein length, and gene duplication. We found that gene expression is correlated with rates of sequence divergence and codon bias, suggesting that natural selection is acting on Picea protein-coding genes for translational efficiency. Gene expression, rates of sequence divergence, and codon bias are correlated with the size of gene families, with large multicopy gene families having, on average, a lower expression level and breadth, lower codon bias, and higher rates of sequence divergence than single-copy gene families. Tissue-specific patterns of gene expression were more common in large gene families with large gene expression divergence than in single-copy families. Recent family expansions combined with large gene expression variation in paralogs and increased rates of sequence evolution suggest that some Picea gene families are rapidly evolving to cope with biotic and abiotic stress. Our study highlights the importance of gene expression and natural selection in shaping the evolution of protein-coding genes in Picea species, and sets the ground for further studies investigating the evolution of individual gene families in gymnosperms.

  • 30. Dixon, Christopher J
    et al.
    Schoenswetter, Peter
    Suda, Jan
    Wiedermann, Magdalena M
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Schneeweiss, Gerald M
    Reciprocal Pleistocene origin and postglacial range formation of an allopolyploid and its sympatric ancestors (Androsace adfinis group, Primulaceae)2009In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 50, no 1, p. 74-83Article in journal (Refereed)
    Abstract [en]

    The biogeographic history of polyploids and their lower-ploid ancestors is an important feature to achieve a better understanding of polyploid evolution. This is exemplified here using the ecologically congruent members of the Androsace adfinis group (Primulaceae) endemic to the southwestern European Alps. Employing relative genome size, AFLP fingerprint and chloroplast sequence haplotype data, we show that Androsace brigantiaca is a recent (probably no more than 0.2 million years) allopolyploid derivative of the geographically close A adfinis and A puberula, which formed reciprocally in a comparatively restricted area in the southern Southwestern Alps. Bayesian admixture analysis-also of artificial additive AFLP profiles-shows that the nuclear genome of A. brigantiaca is significantly biased towards the puberula-genome irrespective of maternal parentage. Nevertheless, there is no evidence for genetic interaction (hybridization, introgression) of A brigantiaca with either of its ancestors, including the widely sympatric A. puberula. Sympatry might be facilitated by ecological displacement on a local scale or might be a transitory phase on the way to competitive replacement via, for instance, polyploid superiority.

  • 31. Dobbins, Sara E.
    et al.
    Broderick, Peter
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Feychting, Maria
    Johansen, Christoffer
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Schramm, Johannes
    Olver, Bianca
    Lloyd, Amy
    Ma, Yussanne P.
    Hosking, Fay J.
    Lönn, Stefan
    Ahlbom, Anders
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schoemaker, Minouk J.
    Hepworth, Sarah J.
    Hoffmann, Per
    Muehleisen, Thomas W.
    Noethen, Markus M.
    Moebus, Susanne
    Eisele, Lewin
    Kosteljanetz, Michael
    Muir, Kenneth
    Swerdlow, Anthony
    Simon, Matthias
    Houlston, Richard S.
    Common variation at 10p12.31 near MLLT10 influences meningioma risk2011In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 43, no 9, p. 825-827Article in journal (Refereed)
    Abstract [en]

    To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.

  • 32. Dongre, Mitesh
    et al.
    Khatri, Neelam
    Dureja, Chetna
    Raychaudhuri, Saumya
    Alanine-scanning mutagenesis of selected residues in the N-terminal region alters the functionality of LuxO: lessons from a natural variant LuxOPL91.2011In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 60, no Pt 6, p. 856-60Article in journal (Refereed)
  • 33. Dongre, Mitesh
    et al.
    Tripathi, Ranjana
    Jain, Vibhu
    Raychaudhuri, Saumya
    Functional independence of a variant LuxOPL91 from a non-O1 non-O139 Vibrio cholerae over the activity of CsrA and Fis.2008In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 57, no Pt 8, p. 1041-5Article in journal (Refereed)
  • 34. Drotz, Marcus K
    et al.
    Brodin, Tomas
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Nilsson, Anders N
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Changing Names with Changed Address: Integrated Taxonomy and Species Delimitation in the Holarctic Colymbetes paykulli Group (Coleoptera: Dytiscidae)2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0143577Article in journal (Refereed)
    Abstract [en]

    Species delimitation of geographically isolated forms is a long-standing problem in less studied insect groups. Often taxonomic decisions are based directly on morphologic variation, and lack a discussion regarding sample size and the efficiency of migration barriers or dispersal/migration capacity of the studied species. These problems are here exemplified in a water beetle complex from the Bering Sea region that separates North America from Eurasia. Only a few sampled specimens occur from this particular area and they are mostly found in museum and private collections. Here we utilize the theory of integrated taxonomy to discuss the speciation of the Holarctic Colymbetes paykulli water beetle complex, which historically has included up to five species of which today only two are recognized. Three delimitation methods are used; landmark based morphometry of body shape, variation in reticulation patterns of the pronotum exo-skeleton and sequence variation of the partial mitochondrial gene Cyt b. Our conclusion is that the Palearctic and Nearctic populations of C. paykulli are given the status of separate species, based on the fact that all methods showed significant separation between populations. As a consequence the name of the Palearctic species is C. paykulli Erichson and the Nearctic species should be known as C. longulus LeConte. There is no clear support for delineation between Palearctic and Nearctic populations of C. dahuricus based on mtDNA. However, significant difference in size and reticulation patterns from the two regions is shown. The combined conclusion is that the C. dahuricus complex needs a more thorough investigation to fully disentangle its taxonomic status. Therefore it is here still regarded as a Holarctic species. This study highlights the importance to study several diagnosable characters that has the potential to discriminate evolutionary lineage during speciation.

  • 35. Du, Qingzhang
    et al.
    Tian, Jiaxing
    Yang, Xiaohui
    Pan, Wei
    Xu, Baohua
    Li, Bailian
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Zhang, Deqiang
    Identification of additive, dominant, and epistatic variation conferred by key genes in cellulose biosynthesis pathway in Populus tomentosa2015In: DNA research, ISSN 1340-2838, E-ISSN 1756-1663, Vol. 22, no 1, p. 53-67Article in journal (Refereed)
    Abstract [en]

    Economically important traits in many species generally show polygenic, quantitative inheritance. The components of genetic variation (additive, dominant and epistatic effects) of these traits conferred by multiple genes in shared biological pathways remain to be defined. Here, we investigated 11 full-length genes in cellulose biosynthesis, on 10 growth and wood-property traits, within a population of 460 unrelated Populus tomentosa individuals, via multi-gene association. To validate positive associations, we conducted single-marker analysis in a linkage population of 1,200 individuals. We identified 118, 121, and 43 associations (P < 0.01) corresponding to additive, dominant, and epistatic effects, respectively, with low to moderate proportions of phenotypic variance (R-2). Epistatic interaction models uncovered a combination of three non-synonymous sites from three unique genes, representing a significant epistasis for diameter at breast height and stem volume. Single-marker analysis validated 61 associations (false discovery rate, Q <= 0.10), representing 38 SNPs from nine genes, and its average effect (R-2 = 3.8%) nearly 2-fold higher than that identified with multi-gene association, suggesting that multi-gene association can capture smaller individual variants. Moreover, a structural gene-gene network based on tissue-specific transcript abundances provides a better understanding of the multi-gene pathway affecting tree growth and lignocellulose biosynthesis. Our study highlights the importance of pathway-based multiple gene associations to uncover the nature of genetic variance for quantitative traits and may drive novel progress in molecular breeding.

  • 36.
    Duan, Chen
    et al.
    Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Guo, Xiong
    Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Zhang, Xiao-Dong
    First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Yu, Han-Jie
    Northwest University, Xi'an, Shaanxi, China.
    Yan, Hua
    Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Gao, Ying
    Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Ma, Wei-Juan
    Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Gao, Zong-Qiang
    Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Xu, Peng
    Xi'an Red Cross Hospital, Xi'an, Shaanxi, China.
    Lammi, Mikko
    University of Kuopio, Kuopio, Finland.
    Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease.2010In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, no 3, p. 771-780, article id 20131229Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the differences in gene expression profiles of adult articular cartilage from patients with Kashin-Beck disease (KBD) versus those with primary knee osteoarthritis (OA).

    METHODS: The messenger RNA expression profiles of articular cartilage from patients with KBD, diagnosed according to the clinical criteria for KBD in China, were compared with those of cartilage from patients with OA, diagnosed according to the Western Ontario and McMaster Universities OA Index. Total RNA was isolated separately from 4 pairs of the KBD and OA cartilage samples, and the expression profiles were evaluated by Agilent 4x44k Whole Human Genome density oligonucleotide microarray analysis. The microarray data for selected transcripts were confirmed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification.

    RESULTS: For 1.2 x 10(4) transcripts, corresponding to 58.4% of the expressed transcripts, 2-fold changes in differential expression were revealed. Expression levels higher in KBD than in OA samples were observed in a mean + or - SD 6,439 + or - 1,041 (14.6 + or - 2.4%) of the transcripts, and expression levels were lower in KBD than in OA samples in 6,147 + or - 1,222 (14.2 + or - 2.8%) of the transcripts. After application of the selection criteria, 1.85% of the differentially expressed genes (P < 0.001 between groups) were detected. These included 233 genes, of which 195 (0.4%) were expressed at higher levels and 38 (0.08%) were expressed at lower levels in KBD than in OA cartilage. Comparisons of the quantitative RT-PCR data supported the validity of our microarray data.

    CONCLUSION: Differences between KBD and OA cartilage exhibited a similar pattern among all 4 of the pairs examined, indicating the presence of disease mechanisms, mainly chondrocyte matrix metabolism, cartilage degeneration, and apoptosis induction pathways, which contribute to cartilage destruction in KBD.

  • 37.
    Eriksson, Mats
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moseley, Jeffrey L
    Tottey, Stephen
    Del Campo, Jose A
    Quinn, Jeanette
    Kim, Youngbae
    Merchant, Sabeeha
    Genetic dissection of nutritional copper signaling in chlamydomonas distinguishes regulatory and target genes2004In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 168, no 2, p. 795-807Article in journal (Refereed)
    Abstract [en]

    A genetic screen for Chlamydomonas reinhardtii mutants with copper-dependent growth or nonphotosynthetic phenotypes revealed three loci, COPPER RESPONSE REGULATOR 1 (CRR1), COPPER RESPONSE DEFECT 1 (CRD1), and COPPER RESPONSE DEFECT 2 (CRD2), distinguished as regulatory or target genes on the basis of phenotype. CRR1 was shown previously to be required for transcriptional activation of target genes like CYC6, CPX1, and CRD1, encoding, respectively, cytochrome c(6) (which is a heme-containing substitute for copper-containing plastocyanin), coproporphyrinogen III oxidase, and Mg-protoporphyrin IX monomethylester cyclase. We show here that CRR1 is required also for normal accumulation of copper proteins like plastocyanin and ferroxidase in copper-replete medium and for apoplastocyanin degradation in copper-deficient medium, indicating that a single pathway controls nutritional copper homeostasis at multiple levels. CRR1 is linked to the SUPPRESSOR OF PCY1-AC208 13 (SOP13) locus, which corresponds to a gain-of-function mutation resulting in copper-independent expression of CYC6. CRR1 is required also for hypoxic growth, pointing to a physiologically meaningful regulatory connection between copper deficiency and hypoxia. The growth phenotype of crr1 strains results primarily from secondary iron deficiency owing to reduced ferroxidase abundance, suggesting a role for CRR1 in copper distribution to a multicopper ferroxidase involved in iron assimilation. Mutations at the CRD2 locus also result in copper-conditional iron deficiency, which is consistent with a function for CRD2 in a pathway for copper delivery to the ferroxidase. Taken together, the observations argue for a specialized copper-deficiency adaptation for iron uptake in Chlamydomonas.

  • 38.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Moqtaderi, Zarmik
    Fan, Xiaochun
    Lu, Jian
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Struhl, Kevin
    Byström, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Iwr1 protein is important for preinitiation complex formation by all three nuclear RNA polymerases in Saccharomyces cerevisiae2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, p. e20829-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Iwr1, a protein conserved throughout eukaryotes, was originally identified by its physical interaction with RNA polymerase (Pol) II.

    PRINCIPAL FINDINGS: Here, we identify Iwr1 in a genetic screen designed to uncover proteins involved in Pol III transcription in S. cerevisiae. Iwr1 is important for Pol III transcription, because an iwr1 mutant strain shows reduced association of TBP and Pol III at Pol III promoters, a decreased rate of Pol III transcription, and lower steady-state levels of Pol III transcripts. Interestingly, an iwr1 mutant strain also displays reduced association of TBP to Pol I-transcribed genes and of both TBP and Pol II to Pol II-transcribed promoters. Despite this, rRNA and mRNA levels are virtually unaffected, suggesting a post-transcriptional mechanism compensating for the occupancy defect.

    CONCLUSIONS: Thus, Iwr1 plays an important role in preinitiation complex formation by all three nuclear RNA polymerases.

  • 39.
    Faucillion, Marie-Line
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Increased expression of X-linked genes in mammals is associated with a higher stability of transcripts and an increased ribosome density2015In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 7, no 4, p. 1039-1052Article in journal (Refereed)
    Abstract [en]

    Mammalian sex chromosomes evolved from the degeneration of one homolog of a pair of ancestral autosomes, the proto-Y. This resulted in a gene dose imbalance that is believed to be restored (partially or fully) through up-regulation of gene expression from the single active X-chromosome in both sexes by a dosage compensatory mechanism. We analyzed multiple genome-wide RNA stability datasets and found significantly longer average half-lives for X-chromosome transcripts than for autosomal transcripts in various human cell lines, both male and female, and in mice. Analysis of ribosome profiling data shows that ribosome density is higher on X-chromosome transcripts than on autosomal transcripts in both humans and mice, suggesting that the higher stability is causally linked to a higher translation rate. Our results and observations are in accordance with a dosage compensatory upregulation of expressed X-linked genes. We therefore propose that differential mRNA stability and translation rates of the autosomes and sex chromosomes contribute to an evolutionarily conserved dosage compensation mechanism in mammals.

  • 40.
    Figueiredo, Margarida L. A.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Kim, Maria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Philip, Philge
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Computational Life Science Cluster (CLiC), Umeå University, SE-90187 Umeå, Sweden.
    Allgardsson, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Division of CBRN Defence and Security, FOI, Swedish Defence Research Agency, Sweden.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Computational Life Science Cluster (CLiC), Umeå UniversityUmeå, Sweden; Division of CBRN Defence and Security, FOI, Swedish Defence Research Agency, Sweden.
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Non-coding roX RNAs prevent the binding of the MSL-complex to heterochromatic regions2014In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 12, p. e1004865-Article in journal (Refereed)
    Abstract [en]

    Long non-coding RNAs contribute to dosage compensation in both mammals and Drosophila by inducing changes in the chromatin structure of the X-chromosome. In Drosophila melanogaster, roX1 and roX2 are long non-coding RNAs that together with proteins form the male-specific lethal (MSL) complex, which coats the entire male X-chromosome and mediates dosage compensation by increasing its transcriptional output. Studies on polytene chromosomes have demonstrated that when both roX1 and roX2 are absent, the MSL-complex becomes less abundant on the male X-chromosome and is relocated to the chromocenter and the 4thchromosome. Here we address the role of roX RNAs in MSL-complex targeting and the evolution of dosage compensation in Drosophila. We performed ChIP-seq experiments which showed that MSL-complex recruitment to high affinity sites (HAS) on the X-chromosome is independent of roX and that the HAS sequence motif is conserved in D. simulans. Additionally, a complete and enzymatically active MSL-complex is recruited to six specific genes on the 4thchromosome. Interestingly, our sequence analysis showed that in the absence of roX RNAs, the MSL-complex has an affinity for regions enriched in Hoppel transposable elements and repeats in general. We hypothesize that roX mutants reveal the ancient targeting of the MSL-complex and propose that the role of roX RNAs is to prevent the binding of the MSL-complex to heterochromatin.

  • 41.
    Figueiredo, Margarida L A
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Philip, Philge
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    HP1a Recruitment to Promoters Is Independent of H3K9 Methylation in Drosophila melanogaster2012In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 8, no 11, p. e1003061-Article in journal (Refereed)
    Abstract [en]

    Heterochromatin protein 1 (HP1) proteins, recognized readers of the heterochromatin mark methylation of histone H3 lysine 9 (H3K9me), are important regulators of heterochromatin-mediated gene silencing and chromosome structure. In Drosophila melanogaster three histone lysine methyl transferases (HKMTs) are associated with the methylation of H3K9: Su(var)3-9, Setdb1, and G9a. To probe the dependence of HP1a binding on H3K9me, its dependence on these three HKMTs, and the division of labor between the HKMTs, we have examined correlations between HP1a binding and H3K9me patterns in wild type and null mutants of these HKMTs. We show here that Su(var)3-9 controls H3K9me-dependent binding of HP1a in pericentromeric regions, while Setdb1 controls it in cytological region 2L:31 and (together with POF) in chromosome 4. HP1a binds to the promoters and within bodies of active genes in these three regions. More importantly, however, HP1a binding at promoters of active genes is independent of H3K9me and POF. Rather, it is associated with heterochromatin protein 2 (HP2) and open chromatin. Our results support a hypothesis in which HP1a nucleates with high affinity independently of H3K9me in promoters of active genes and then spreads via H3K9 methylation and transient looping contacts with those H3K9me target sites.

  • 42.
    Frida, Jonsson
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Underlying genetic mechanisms of hereditary dystrophies in retina and cornea2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Inherited retinal and corneal dystrophies represent a group of disorders with great genetic heterogeneity. Over 250 genes are associated with retinal diseases and 16 genes are causative of corneal dystrophies. This thesis is focused on finding the genetic causes of corneal dystrophy, Leber congenital amaurosis (LCA), Stargardt disease and retinitis pigmentosa in families from northern Sweden.  By whole exome sequencing a novel mutation, c.2816C>T, p.Thr939Ile, in Collagen Type XVII, Alpha 1 chain, COL17A1, gene was identified in several families with epithelial recurrent erosion dystrophy (ERED). We showed that the COL17A1 protein is expressed in the basement membrane of the cornea, explaining the mutation involvement in the corneal symptoms. We could link all the families in this study to a couple born in the late 1700s confirming a founder mutation in northern Sweden. Our finding highlights role of COL17A1 in ERED and suggests screening of this gene in patients with similar phenotype worldwide. Furthermore the genetic causes in several retinal degenerations were identified. In one family with two recessive disorders, LCA and Stargardt disease, a novel stop mutation, c.2557C>T, p.Gln853Stop, was detected in all LCA patients. In the Stargardt patients two intronic variants, the novel c.4773+3A>G and c.5461-10T>C, were detected in the ABCA4 gene. One individual was homozygous for the known variant c.5461-10T>C and the other one was compound heterozygote with both variants present. Both variants, c.4773+3A>G and c.5461-10T>C caused exon skipping in HEK293T cells demonstrated by in vitro splice assay, proving their pathogenicity in Stargardt disease. Finally, in recessive retinitis pigmentosa, Bothnia Dystrophy (BD), we identified a second mutation in the RLBP1 gene, c.677T>A, p.Met226Lys. Thus, BD is caused not only by common c.700C>T variant but also by homozygosity of c.677T>A or compound heterozygosity. Notably, known variant, c.40C>T, p.R14W in the CAIV gene associated with a dominant retinal dystrophy RP17 was detected in one of the compound BD heterozygote and his unaffected mother. This variant appears to be a benign variant in the population of northern Sweden.

    In conclusion, novel genetic causes of retinal dystrophies in northern Sweden were found demonstrating the heterogeneity and complexity of retinal diseases. Identification of the genetic defect in COL17A1 in the corneal dystrophy contributes to understanding ERED pathogenesis and encourages refinement of IC3D classification. Our results provide valuable information for future molecular testing and genetic counselling of the families.

  • 43.
    Funda, Tomas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Forest Genetics and Plant Physiology, UPSCSwedish University of Agricultural Sciences, Umeå, Sweden.
    Wennström, Ulfstand
    Almqvist, Curt
    Andersson Gull, Bengt
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Mating dynamics of Scots pine in isolation tents2016In: Tree Genetics & Genomes, ISSN 1614-2942, E-ISSN 1614-2950, Vol. 12, no 6, article id 112Article in journal (Refereed)
    Abstract [en]

    Seed orchards are forest tree production populations for supplying the forest industry with consistent and abundant seed crops of superior genetic quality. However, genetic quality can be severely affected by non-random mating among parents and the occurrence of background pollination. This study analyzed mating structure and background pollination in six large isolation tents established in a clonal Scots pine seed orchard in northern Sweden. The isolation tents were intended to form a physical barrier against background pollen and induce earlier flowering relative to the surrounding trees. We scored flowering phenology inside and outside the tents and tracked airborne pollen density inside and outside the seed orchard in three consecutive pollination seasons. We genotyped 5683 offspring collected from the tents and open controls using nine microsatellite loci, and assigned paternity using simple exclusion method. We found that tent trees shed pollen and exhibited maximum female receptivity approximately 1 week earlier than trees in open control. The majority of matings in tents (78.3 %) occurred at distances within two trees apart (about 5 m). Self-fertilization was relatively high (average 21.8 %) in tents without supplemental pollination (SP), but it was substantially reduced in tents with SP (average 7.7 %). Pollen contamination was low in open controls (4.8-7.1 %), and all tents remained entirely free of foreign pollen. Our study demonstrates that tent isolation is effective in blocking pollen immigration and in manipulating flowering phenology. When complimented with supplemental pollination, it could become a useful seed orchard management practice to optimize the gain and diversity of seed orchard crops.

  • 44.
    Gao, Jie
    et al.
    State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.
    Wang, Baosheng
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Mao, Ian-Feng
    State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.
    Ingvarsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Zeng, Qing-Yin
    State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.
    Demography and speciation history of the homoploid hybrid pine Pinus densata on the Tibetan Plateau2012In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 21, no 19, p. 4811-4827Article in journal (Refereed)
    Abstract [en]

    Pinus densata is an ecologically successful homoploid hybrid that inhabits vast areas of heterogeneous terrain on the south-eastern Tibetan Plateau as a result of multiple waves of colonization. Its region of origin, route of colonization onto the plateau and the directions of introgression with its parental species have previously been defined, but little is known about the isolation and divergence history of its populations. In this study, we surveyed nucleotide polymorphism over eight nuclear loci in 19 representative populations of P. densata and its parental species. Using this information and coalescence simulations, we assessed the historical changes in its population size, gene flow and divergence in time and space. The results indicate a late Miocene origin for P. densata associated with the recent uplift of south-eastern Tibet. The subsequent differentiation between geographical regions of this species began in the late Pliocene and was induced by regional topographical changes and Pleistocene glaciations. The ancestral P. densata population had a large effective population size but the central and western populations were established by limited founders, suggesting that there were severe bottlenecks during the westward migration out of the ancestral hybrid zone. After separating from their ancestral populations, population expansion occurred in all geographical regions especially in the western range. Gene flow in P. densata was restricted to geographically neighbouring populations, resulting in significant differentiation between regional groups. The new information on the divergence and demographic history of P. densata reported herein enhances our understanding of its speciation process on the Tibetan Plateau.

  • 45.
    Goretti, Daniela
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Biosciences, University of Milan, Via Celoria 26, Milan, Italy.
    Martignago, Damiano
    Landini, Martina
    Brambilla, Vittoria
    Gomez-Ariza, Jorge
    Gnesutta, Nerina
    Galbiati, Francesca
    Collani, Silvio
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Takagi, Hiroki
    Terauchi, Ryohei
    Mantovani, Roberto
    Fornara, Fabio
    Transcriptional and Post-transcriptional Mechanisms Limit Heading Date 1 (Hd1) Function to Adapt Rice to High Latitudes2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 1, article id e1006530Article in journal (Refereed)
    Abstract [en]

    Rice flowering is controlled by changes in the photoperiod that promote the transition to the reproductive phase as days become shorter. Natural genetic variation for flowering time has been largely documented and has been instrumental to define the genetics of the photoperiodic pathway, as well as providing valuable material for artificial selection of varieties better adapted to local environments. We mined genetic variation in a collection of rice varieties highly adapted to European regions and isolated distinct variants of the long day repressor HEADING DATE 1 (Hd1) that perturb its expression or protein function. Specific variants allowed us to define novel features of the photoperiodic flowering pathway. We demonstrate that a histone fold domain scaffold formed by GRAIN YIELD, PLANT HEIGHT AND HEADING DATE 8 (Ghd8) and several NF-YC subunits can accommodate distinct proteins, including Hd1 and PSEUDO RESPONSE REGULATOR 37 (PRR37), and that the resulting OsNF-Y complex containing Hd1 can bind a specific sequence in the promoter of HEADING DATE 3A (Hd3a). Artificial selection has locally favored an Hd1 variant unable to assemble in such heterotrimeric complex. The causal polymorphism was defined as a single conserved lysine in the CCT domain of the Hd1 protein. Our results indicate how genetic variation can be stratified and explored at multiple levels, and how its description can contribute to the molecular understanding of basic developmental processes.

  • 46. Gouzi, Jean Y.
    et al.
    Moressis, Anastasios
    Walker, James A.
    Apostolopoulou, Anthi A.
    Palmer, Ruth H.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Bernards, Andre
    Skoulakis, Efthimios M. C.
    The receptor tyrosine kinase alk controls neurofibromin functions in drosophila growth and learning2011In: PLoS Genetics, ISSN 1553-7390, Vol. 7, no 9, p. e1002281-Article in journal (Refereed)
    Abstract [en]

    Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in several cancers, but with largely unknown physiological functions. We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant phenotypes. These results identify dAlk as an upstream activator of dNf1-regulated Ras signaling responsible for several dNf1 defects, and they implicate human Alk as a potential therapeutic target in NF1.

  • 47.
    Hall, David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå Plant Science Centre, Department of Forest Genetics and Plant PhysiologySwedish University of Agricultural Sciences, Umeå, Sweden.
    Hallingbäck, Henrik R.
    Wu, Harry X.
    Estimation of number and size of QTL effects in forest tree traits2016In: Tree Genetics & Genomes, ISSN 1614-2942, E-ISSN 1614-2950, Vol. 12, no 6, article id 110Article in journal (Refereed)
    Abstract [en]

    Mapping the genetic architecture of forest tree traits is important in order to understand the evolutionary forces that have shaped these traits and to facilitate the development of genomic-based breeding strategies. We examined the number, size, and distribution of allelic effects influencing eight types of traits using 30 published mapping studies (linkage and association mapping) in forest trees. The sizes of allelic effects, measured as the phenotypic variance explained, generally showed a severely right-skewed distribution. We estimated the numbers of underlying causal effects (n(qtl)) for different trait categories by improving a method previously developed by Otto and Jones (Genetics 156: 2093-2107, 2000). Estimates of n(qtl) based on association mapping studies were generally higher (median at 643) than those based on linkage mapping (median at 33). Comparisons with simulated linkage and association mapping data suggested that the lower n(qtl) estimates for the linkage mapping studies could partly be explained by fewer causal loci segregating within the full-sib family populations normally used, but also by the cosegregation of causal loci due to limited recombination. Disease resistance estimates based on linkage mapping studies had the lowest median of four underlying effects, while growth traits based on association mapping had about 580 effects. Theoretically, the capture of 50% of the genetic variation would thus require a population size of about 200 for disease resistance in linkage mapping, while growth traits in association mapping would require about 25,000. The adequacy and reliability of the improved method was successfully verified by applying it to the simulated data.

  • 48.
    Hall, David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Ma, Xiao-Fei
    Program in Evolutionary Functional Genomics, Evolutionary Biology Center, Uppsala University.
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Adaptive evolution of the Populus tremula photoperiod pathway2011In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 20, no 7, p. 1463-1474Article in journal (Refereed)
    Abstract [en]

    Environmental cues entrain the circadian clock, a core component of the photoperiod pathway in plants, to daily and seasonal changes. The circadian clock mediates input signals from light and temperature receptors to downstream target genes through feedback loops. Several studies have shown that a correct timing of the circadian system is a fitness advantage and genes in photoperiod network have been implied to evolve in response to the diversifying selection in heterogeneous environment. In an attempt to quantify the extent of the historical patterns of selection on genes in the photoperiod pathway in the widely distributed tree species European aspen (Populus tremula) we obtained sequences for twenty-five of the genes in the network and these genes were compared to patterns of nucleotide diversity in 77 randomly chosen genes from across the genome of P. tremula. We found a significant reduction in synonymous diversity in photoperiod genes while non-synonymous diversity was in line with data from control genes. A substantial fraction of the genes show signs of selection, with eight genes showing signs of rapid protein evolution. In contrast to our expectations, genes closely associated with the core circadian clock show rapid protein evolution despite their central position in the pathway. Furthermore, selection on non-synonymous mutations is negatively correlated with synonymous diversity across all genes, indicating the action of recurrent selective sweeps.

  • 49.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Klar, Joakim
    Ameur, Adam
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sorensen, Karen
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description2016In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 17, article id 61Article in journal (Refereed)
    Abstract [en]

    Background: Mutations in MYLK cause non- syndromic familial thoracic aortic aneurysms and dissections (FTAAD). Very little is known about the phenotype of affected families. We sought to characterize the aortic disease and the presence of other vascular abnormalities in FTAAD caused by a deletion in MYLK and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers.

    Methods: We studied FTAAD in a 5-generation family that included 19 living members. Exome sequencing was performed to identify the underlying gene defect. Aortic elastic properties measured by TTE, MRI and pulse wave velocity were then compared between mutation carriers and non-carriers.

    Results: Exome sequencing led to the identification of a 2-bp deletion in MYLK (c3272_ 3273del, p. Ser1091*) that led to a premature stop codon and nonsense-mediated decay. Eleven people were mutation carriers and eight people were non-carriers. Five aortic ruptures or dissections occurred in this family, with two survivors. There were no differences in aortic diameter or stiffness between carriers and non-carriers of the mutation.

    Conclusions: Individuals carrying this deletion in MYLK have a high risk of presenting with an acute aortic dissection or rupture. Aortic events occur over a wide range of ages and are not always preceded by obvious aortic dilatation. Aortic elastic properties do not differ between carriers and non-carriers of this mutation, rendering it uncertain whether and when carriers should undergo elective prophylactic surgery.

  • 50.
    Hed, Helen
    Umeå University.
    Opportunity for selection during the 17th-19thcenturies in the diocese of Linkoping as estimated with Crow's Index in a population of clergymen's wives1984In: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 34, no 6, p. 378-387Article in journal (Refereed)
1234 1 - 50 of 189
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