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  • 151. Rogers, AS
    et al.
    Andersson Escher, Stefan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Pasetto, C
    Rosato, E
    Costa, R
    Kyriacou, CP
    A mutation in Drosophila simulans that lengthens the circadian period of locomotor activity2004In: Genetica, ISSN 0016-6707, E-ISSN 1573-6857, Vol. 120, no 1-3, p. 223-232Article in journal (Refereed)
    Abstract [en]

    The length of the Thr-Gly repeat within the period gene of Drosophilids, coevolves with its immediate flanking region to maintain the temperature compensation of the fly circadian clock. In Drosophila simulans, balancing selection appears to maintain a polymorphism in this region, with three repeat lengths carrying 23, 24 or 25 Thr-Gly pairs, each in complete linkage disequilibrium with a distinctive flanking region amino acid moiety. We wondered whether separating a specific length repeat from its associated flanking haplotype might have functional implications for the circadian clock. We fortuitously discovered a population of flies collected in Kenya, in which a chimeric Thr-Gly haplotype was segregating that carried the (Thr-Gly)(24) repeat, but the flanking region of a (Thr-Gly) 23 allele. One of the five isofemale lines that carried this 'mutant' Thr-Gly sequence showed a dramatically long and temperature-sensitive free-running circadian period. This phenotype was mapped to the X chromosome, close to the D. simulans per gene, but there was also a significant effect of a modifying autosomal locus or loci. It seems remarkable that such a mutant phenotype should be discovered in a screen of chimeric Thr-Gly regions.

  • 152.
    Rudin, Dag
    Umeå University.
    The isozyme technique - a short-cut to the genes of our forest trees?: illustrations using Pinus sylvestris L1977Doctoral thesis, comprehensive summary (Other academic)
  • 153.
    Sabouri, Nasim
    et al.
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
    McDonald, Karin R
    Webb, Christopher J
    Cristea, Ileana M
    Zakian, Virginia A
    DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase2012In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 26, no 6, p. 581-593Article in journal (Refereed)
    Abstract [en]

    Replication forks encounter impediments as they move through the genome, including natural barriers due to stable protein complexes and highly transcribed genes. Unlike lesions generated by exogenous damage, natural barriers are encountered in every S phase. Like humans, Schizosaccharomyces pombe encodes a single Pif1 family DNA helicase, Pfh1. Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II. In addition, converged replication forks accumulated at all of these sites in the absence of Pfh1. The effects of Pfh1 on DNA replication are likely direct, as it had high binding to sites whose replication was impaired in its absence. Replication in the absence of Pfh1 resulted in DNA damage specifically at those sites that bound high levels of Pfh1 in wild-type cells and whose replication was slowed in its absence. Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks. Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites.

  • 154.
    Sahlman, Janne
    et al.
    Seinäjoki Central Hospital, Seinäjoki, Finland.
    Pitkänen, Marja
    University Hospital of Kuopio, Kuopio, Finland.
    Prockop, Darwin
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Arita, Machiko
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Li, Shi-Wu
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Långsjö, Teemu
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Puustjärvi, Kaija
    Helsinki University Hospital, Helsinki, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    A human COL2A1 gene with an Arg519Cys mutation causes osteochondrodysplasia in transgenic mice.2004In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 50, no 10, p. 3153-3160, article id 15476249Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: An arginine-to-cysteine substitution at position 519 of the COL2A1 gene causes early generalized osteoarthritis with mild chondrodysplasia in humans. In this study, a human COL2A1 gene with the same mutation was introduced into a murine genome having 1 or no alleles of the murine Col2a1 gene, and the skeletal phenotypes of the transgenic mice were compared with those of control mice.

    METHODS: Mice with 1 allele of the normal murine Col2a1 gene and 1 allele of the mutated human COL2A1 gene (n = 10), those with no murine Col2a1 gene and 2 alleles of the mutated human COL2A1 gene (n = 13), those with no murine Col2a1 gene and only 1 allele of the mutated COL2A1 gene (n = 9), and normal control mice (n = 11) were studied for skeletal abnormalities, using radiographic imaging and light microscopic analyses of histologic sections. The collagen network of cartilage was also investigated with transmission electron microscopy.

    RESULTS: At 2 months of age, all transgenic mice had dysplastic changes in their long bones, flattened vertebral bodies, and osteoarthritic changes in their joints. The intervertebral discs of the transgenic animals were degenerated, and their histologic structure was disturbed. The changes were more severe in mice with no murine Col2a1 allele.

    CONCLUSION: The human COL2A1 gene with the Arg519Cys mutation causes osteochondrodysplasia in mice, as it does in humans.

  • 155. Salojarvi, Jarkko
    et al.
    Smolander, Olli-Pekka
    Nieminen, Kaisa
    Rajaraman, Sitaram
    Safronov, Omid
    Safdari, Pezhman
    Lamminmaki, Airi
    Immanen, Juha
    Lan, Tianying
    Tanskanen, Jaakko
    Rastas, Pasi
    Amiryousefi, Ali
    Jayaprakash, Balamuralikrishna
    Kammonen, Juhana I.
    Hagqvist, Risto
    Eswaran, Gugan
    Ahonen, Viivi Helena
    Serra, Juan Alonso
    Asiegbu, Fred O.
    Barajas-Lopez, Juan de Dios
    Blande, Daniel
    Blokhina, Olga
    Blomster, Tiina
    Broholm, Suvi
    Brosche, Mikael
    Cui, Fuqiang
    Dardick, Chris
    Ehonen, Sanna E.
    Elomaa, Paula
    Escamez, Sacha
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Fagerstedt, Kurt V.
    Fujii, Hiroaki
    Gauthier, Adrien
    Gollan, Peter J.
    Halimaa, Pauliina
    Heino, Pekka I.
    Himanen, Kristiina
    Hollender, Courtney
    Kangasjarvi, Saijaliisa
    Kauppinen, Leila
    Kelleher, Colin T.
    Kontunen-Soppela, Sari
    Koskinen, J. Patrik
    Kovalchuk, Andriy
    Karenlampi, Sirpa O.
    Karkonen, Anna K.
    Lim, Kean-Jin
    Leppala, Johanna
    Macpherson, Lee
    Mikola, Juha
    Mouhu, Katriina
    Mahonen, Ari Pekka
    Niinemets, Ulo
    Oksanen, Elina
    Overmyer, Kirk
    Palva, E. Tapio
    Pazouki, Leila
    Pennanen, Ville
    Puhakainen, Tuula
    Poczai, Peter
    Possen, Boy J. H. M.
    Punkkinen, Matleena
    Rahikainen, Moona M.
    Rousi, Matti
    Ruonala, Raili
    van der Schoot, Christiaan
    Shapiguzov, Alexey
    Sierla, Maija
    Sipila, Timo P.
    Sutela, Suvi
    Teeri, Teemu H.
    Tervahauta, Arja I.
    Vaattovaara, Aleksia
    Vahala, Jorma
    Vetchinnikova, Lidia
    Welling, Annikki
    Wrzaczek, Michael
    Xu, Enjun
    Paulin, Lars G.
    Schulman, Alan H.
    Lascoux, Martin
    Albert, Victor A.
    Auvinen, Petri
    Helariutta, Yka
    Kangasjarvi, Jaakko
    Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch2017In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 6, p. 904-912Article in journal (Refereed)
    Abstract [en]

    Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.

  • 156. Sandve, Simen R.
    et al.
    Rohlfs, Rori V.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Subfunctionalization versus neofunctionalization after whole-genome duplication2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 7, p. 908-909Article in journal (Refereed)
  • 157.
    Saura, Anssi
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    A tale of two papers2014In: Hereditas, ISSN 0018-0661, E-ISSN 1601-5223, Vol. 151, no 6, p. 119-122Article in journal (Refereed)
    Abstract [en]

    Two papers published in HEREDITAS between 1921 and 1939 show how the attitude towards race biology changed in the course of the interwar period in the Nordic countries. In the early 1920s race biology was seen to constitute a legitimate science. Ordinary human genetics prevailed, however, over race biology already in the very beginning on the pages of HEREDITAS. Population thinking was introduced into the study of human heredity around the year 1930. It effectively contradicted the concept of the race. Interestingly, HEREDITAS does not carry a single paper on eugenics and sterilization. In 1939 we see a final repudiation of the doctrines on race. Times had changed and the National Socialists had usurped the doctrines of race in Germany.

  • 158.
    Schiffthaler, Bastian
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Bernhardsson, Carolina
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Ingvarsson, Par K.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    BatchMap: A parallel implementation of the OneMap R package for fast computation of F-1 linkage maps in outcrossing species2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0189256Article in journal (Refereed)
    Abstract [en]

    With the rapid advancement of high throughput sequencing, large numbers of genetic markers can be readily and cheaply acquired, but most current software packages for genetic map construction cannot handle such dense input. Modern computer architectures and server farms represent untapped resources that can be used to enable higher marker densities to be processed in tractable time. Here we present a pipeline using a modified version of OneMap that parallelizes over bottleneck functions and achieves substantial speedups for producing a high density linkage map (N = 20,000). Using simulated data we show that the outcome is as accurate as the traditional pipeline. We further demonstrate that there is a direct relationship between the number of markers used and the level of deviation between true and estimated order, which in turn impacts the final size of a genetic map.

  • 159.
    Schwartz, Yuri B.
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Cavalli, Giacomo
    Three-Dimensional Genome Organization and Function in Drosophila2017In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 205, no 1, p. 5-24Article, review/survey (Refereed)
    Abstract [en]

    Understanding how the metazoan genome is used during development and cell differentiation is one of the major challenges in the postgenomic era. Early studies in Drosophila suggested that three-dimensional (3D) chromosome organization plays important regulatory roles in this process and recent technological advances started to reveal connections at the molecular level. Here we will consider general features of the architectural organization of the Drosophila genome, providing historical perspective and insights from recent work. We will compare the linear and spatial segmentation of the fly genome and focus on the two key regulators of genome architecture: insulator components and Polycomb group proteins. With its unique set of genetic tools and a compact, well annotated genome, Drosophila is poised to remain a model system of choice for rapid progress in understanding principles of genome organization and to serve as a proving ground for development of 3D genome-engineering techniques.

  • 160. Schwartz, Yuri B.
    et al.
    Kahn, Tatyana G.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Ohno, Katsuhito
    Bourgon, Richard
    Pirrotta, Vincenzo
    Alternative Epigenetic Chromatin States of Polycomb Target Genes2010In: PLoS Genetics, ISSN 1553-7390, Vol. 6, no 1, p. e1000805-Article in journal (Refereed)
    Abstract [en]

    Polycomb (PcG) regulation has been thought to produce stable long-term gene silencing. Genomic analyses in Drosophila and mammals, however, have shown that it targets many genes, which can switch state during development. Genetic evidence indicates that critical for the active state of PcG target genes are the histone methyltransferases Trithorax (TRX) and ASH1. Here we analyze the repertoire of alternative states in which PcG target genes are found in different Drosophila cell lines and the role of PcG proteins TRX and ASH1 in controlling these states. Using extensive genome-wide chromatin immunoprecipitation analysis, RNAi knockdowns, and quantitative RT-PCR, we show that, in addition to the known repressed state, PcG targets can reside in a transcriptionally active state characterized by formation of an extended domain enriched in ASH1, the N-terminal, but not C-terminal moiety of TRX and H3K27ac. ASH1/TRX N-ter domains and transcription are not incompatible with repressive marks, sometimes resulting in a "balanced" state modulated by both repressors and activators. Often however, loss of PcG repression results instead in a "void" state, lacking transcription, H3K27ac, or binding of TRX or ASH1. We conclude that PcG repression is dynamic, not static, and that the propensity of a target gene to switch states depends on relative levels of PcG, TRX, and activators. N-ter TRX plays a remarkable role that antagonizes PcG repression and preempts H3K27 methylation by acetylation. This role is distinct from that usually attributed to TRX/MLL proteins at the promoter. These results have important implications for Polycomb gene regulation, the "bivalent" chromatin state of embryonic stem cells, and gene expression in development.

  • 161. Scott, Alison Dawn
    et al.
    Stenz, Noah W. M.
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Baum, David A.
    Whole genome duplication in coast redwood (Sequoia sempervirens) and its implications for explaining the rarity of polyploidy in conifers2016In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 211, no 1, p. 186-193Article in journal (Refereed)
    Abstract [en]

    Polyploidy is common and an important evolutionary factor in most land plant lineages, but it is rare in gymnosperms. Coast redwood (Sequoia sempervirens) is one of just two polyploid conifer species and the only hexaploid. Evidence from fossil guard cell size suggests that polyploidy in Sequoia dates to the Eocene. Numerous hypotheses about the mechanism of polyploidy and parental genome donors have been proposed, based primarily on morphological and cytological data, but it remains unclear how Sequoia became polyploid and why this lineage overcame an apparent gymnosperm barrier to whole-genome duplication (WGD). We sequenced transcriptomes and used phylogenetic inference, Bayesian concordance analysis and paralog age distributions to resolve relationships among gene copies in hexaploid coast redwood and close relatives. Our data show that hexaploidy in coast redwood is best explained by autopolyploidy or, if there was allopolyploidy, it happened within the Californian redwood clade. We found that duplicate genes have more similar sequences than expected, given the age of the inferred polyploidization. Conflict between molecular and fossil estimates of WGD can be explained if diploidization occurred very slowly following polyploidization. We extrapolate from this to suggest that the rarity of polyploidy in gymnosperms may be due to slow diploidization in this clade.

  • 162. Seehausen, Ole
    et al.
    Butlin, Roger K.
    Keller, Irene
    Wagner, Catherine E.
    Boughman, Janette W.
    Hohenlohe, Paul A.
    Peichel, Catherine L.
    Saetre, Glenn-Peter
    Bank, Claudia
    Brannström, Åke
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Brelsford, Alan
    Clarkson, Chris S.
    Eroukhmanoff, Fabrice
    Feder, Jeffrey L.
    Fischer, Martin C.
    Foote, Andrew D.
    Franchini, Paolo
    Jiggins, Chris D.
    Jones, Felicity C.
    Lindholm, Anna K.
    Lucek, Kay
    Maan, Martine E.
    Marques, David A.
    Martin, Simon H.
    Matthews, Blake
    Meier, Joana I.
    Most, Markus
    Nachman, Michael W.
    Nonaka, Etsuko
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Rennison, Diana J.
    Schwarzer, Julia
    Watson, Eric T.
    Westram, Anja M.
    Widmer, Alex
    Genomics and the origin of species2014In: Nature reviews genetics, ISSN 1471-0056, E-ISSN 1471-0064, Vol. 15, no 3, p. 176-192Article, review/survey (Refereed)
    Abstract [en]

    Speciation is a fundamental evolutionary process, the knowledge of which is crucial for understanding the origins of biodiversity. Genomic approaches are an increasingly important aspect of this research field. We review current understanding of genome-wide effects of accumulating reproductive isolation and of genomic properties that influence the process of speciation. Building on this work, we identify emergent trends and gaps in our understanding, propose new approaches to more fully integrate genomics into speciation research, translate speciation theory into hypotheses that are testable using genomic tools and provide an integrative definition of the field of speciation genomics.

  • 163.
    Seibt, Henrik
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Deciphering control of Mechano-Transcription Activators of σ54-RNA polymerase2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    To survive and proliferate, bacteria have to respond to a plethora of fluctuating signals within their habitats. Transcriptional control is one crucial entry point for such signal-responsive adaption responses. In this thesis I present new insights into the signal-responsive control of two specific transcriptional regulators that belong to a specialized class of mechano-transcriptional regulators. These regulators employ ATP-hydrolysis to engage and remodel σ54-RNA polymerase, which allows transcriptional initiation from the promoters they control. In the first part of my thesis I present findings on DmpR – the obligate activator of genes involved in (methyl)phenol catabolism by Pseudomonas putida. DmpR is a sensory-regulator that can only transition to its active multimeric form upon binding a phenolic compound and ATP. Previous work has established that binding of phenolic effectors by the N-terminal domain of DmpR relieves inter-domain repression of its central ATPase domain and further that a structured inter-domain linker between the phenolic- and ATP-binding domains is involved in coupling these processes. However, the mechanism underlying this coupling remained enigmatic. Here I present evidence that a tyrosine residue of the inter-domain linker (Y233) serves as a gatekeeper to constrain ATP-hydrolysis and phenolic-responsive transcriptional activation by DmpR. A model is presented in which binding of phenolics relocates Y233 from the ATP-binding site to synchronise signal-reception with multimerisation to provide appropriate sensitivity of the transcriptional response. Given that Y233 counterparts are present in many ligand-responsive mechano-transcriptional regulators, the model is likely to be pertinent for numerous members of this family. The finding that an alanine substitution of Y233 enhances transcriptional responses adds a new approach to manipulating the sensitivity of this class of proteins and thereby generate hyper-sensitive detectors of aromatic pollutants for use in safe guarding the environment.

    The second part of my thesis concerns VCA0117 – a master regulator of the type VI contractile nanomachinery of Vibrio cholerae, which it utilizes to introduce toxic proteins into both bacterial and eukaryotic cells. These type VI-mediated properties enable V. cholerae to establish infections and to thrive in niches co-occupied by predators and competing bacteria. VCA0117 is strictly required for functionality of the type VI system through its role in controlling production of a key type VI structural protein called Hcp, which is encoded within two small s54-dependent operons. This regulatory role is conserved in both pandemic and non-pandemic V. cholerae strains. However, while some strains come pre-equipped with a functional system, others do not, and require specific growth conditions of low temperature and high osmolarity for type VI expression. Within this work, integration of these regulatory growth signals was traced to the activity of the promoter controlling a large operon in which many components of the machinery and VCA0117 is itself encoded. This in turn elevates the levels of VCA0117, which is all that is required to overcome the need for the specialized growth conditions of low temperature and/or high osmolarity. A model is presented in which signal integration via the activity of the large operon promoter to elevate levels of VCA0117 ultimately dictates a sufficient supply of the missing Hcp component required for completion of a functional type VI machine. Repercussions of the proposed quantity-based regulatory circuit of VCA0117 for generating bacterial sub-populations that are differentially “fit” for different environmental eventualities are discussed.

  • 164.
    Seibt, Henrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Aung, Kyaw Min
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Ishikawa, Takahiko
    Sjöström, Annika
    Atkinson, Gemma C.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Wai, Sun Nyunt
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Shingler, Victoria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Elevated levels of VCA0117 in response to external signals activates type VI secretion in Vibrio cholerae A1552Manuscript (preprint) (Other academic)
  • 165.
    Seibt, Henrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Sauer, Uwe H.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Shingler, Victoria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    The Y233 gatekeeper of DmpR modulates effector-responsive transcriptional control of δ54-RNA polymerase2019In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 21, no 4, p. 1321-1330Article in journal (Refereed)
    Abstract [en]

    DmpR is the obligate transcriptional activator of genes involved in (methyl)phenol catabolism by Pseudomonas putida. DmpR belongs to the AAA+ class of mechano‐transcriptional regulators that employ ATP‐hydrolysis to engage and remodel σ54‐RNA polymerase to allow transcriptional initiation. Previous work has established that binding of phenolic effectors by DmpR is a prerequisite to relieve interdomain repression and allow ATP‐binding to trigger transition to its active multimeric conformation, and further that a structured interdomain linker between the effector‐ and ATP‐binding domains is involved in coupling these processes. Here, we present evidence from ATPase and in vivo and in vitro transcription assays that a tyrosine residue of the interdomain linker (Y233) serves as a gatekeeper to constrain ATP‐hydrolysis and aromatic effector‐responsive transcriptional activation by DmpR. An alanine substitution of Y233A results in both increased ATPase activity and enhanced sensitivity to aromatic effectors. We propose a model in which effector‐binding relocates Y233 to synchronize signal‐reception with multimerisation to provide physiologically appropriate sensitivity of the transcriptional response. Given that Y233 counterparts are present in many ligand‐responsive mechano‐transcriptional regulators, the model is likely to be pertinent for numerous members of this family and has implications for development of enhanced sensitivity of biosensor used to detect pollutants.

  • 166. Sečenji, M
    et al.
    Lendvai, Á
    Miskolczi, Pal
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Institute of Plant Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
    Kocsy, G
    Gallé, Á
    Szűcs, A
    Hoffmann, B
    Sárvári, É
    Schweizer, P
    Stein, N
    Dudits, D
    Györgyey, J
    Differences in root functions during long-term drought adaptation: comparison of active gene sets of two wheat genotypes2010In: Plant Biology, ISSN 1435-8603, E-ISSN 1438-8677, Vol. 12, no 6, p. 871-882Article in journal (Refereed)
    Abstract [en]

    In an attempt to shed light on the role of root systems in differential responses of wheat genotypes to long-term water limitation, transcriptional differences between two wheat genotypes (Triticum aestivum L., cv. Plainsman V and landrace Kobomugi) were identified during adaptation to moderate water stress at the tillering stage. Differences in organ sizes, water-use efficiency and seed production were detected in plants grown in soil, and root functions were characterised by expression profiling. The molecular genetic background of the behaviour of the two genotypes during this stress was revealed using a cDNA macroarray for transcript profiling of the roots. During a 4-week period of moderate water deficit, a set of up-regulated genes displaying transiently increased expression was identified in young plantlets, mostly in the second week in the roots of Kobomugi, while transcript levels remained constantly high in roots of Plainsman V. These genes encode proteins with various functions, such as transport, protein metabolism, osmoprotectant biosynthesis, cell wall biogenesis and detoxification, and also regulatory proteins. Oxidoreductases, peroxidases and cell wall-related genes were induced significantly only in Plainsman V, while induction of stress- and defence-related genes was more pronounced in Kobomugi. Real-time qPCR analysis of selected members of the glutathione S-transferase gene family revealed differences in regulation of family members in the two genotypes and confirmed the macroarray results. The TaGSTZ gene was stress-activated only in the roots of Kobomugi.

  • 167.
    Shungin, Dmitry
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States of America.
    Deng, Wei Q.
    Varga, Tibor V.
    Luan, Jian'an
    Mihailov, Evelin
    Metspalu, Andres
    Morris, Andrew P.
    Forouhi, Nita G.
    Lindgren, Cecilia
    Magnusson, Patrik K. E.
    Pedersen, Nancy L.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Chu, Audrey Y.
    Justice, Anne E.
    Graff, Mariaelisa
    Winkler, Thomas W.
    Rose, Lynda M.
    Langenberg, Claudia
    Cupples, L. Adrienne
    Ridker, Paul M.
    Wareham, Nicholas J.
    Ong, Ken K.
    Loos, Ruth J. F.
    Chasman, Daniel I.
    Ingelsson, Erik
    Kilpeläinen, Tuomas O.
    Scott, Robert A.
    Mägi, Reedik
    Paré, Guillaume
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
    Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 6, article id e1006812Article in journal (Refereed)
    Abstract [en]

    Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.

  • 168. Sidorenko, D. S.
    et al.
    Zykova, T. Yu
    Khoroshko, V. A.
    Pokholkova, G. , V
    Demakov, S. A.
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Belyaeva, E. S.
    Zhimulev, I. F.
    Polytene chromosomes reflect functional organization of the Drosophila genome2019In: Vavilovski Zhurnal Genetiki i Selektsii, ISSN 2500-0462, Vol. 23, no 2, p. 148-153Article, review/survey (Refereed)
    Abstract [en]

    Polytene chromosomes of Drosophila melanogaster are a convenient model for studying interphase chromosomes of eukaryotes. They are giant in size in comparison with diploid cell chromosomes and have a pattern of cross stripes resulting from the ordered chromatid arrangement. Each region of polytene chromosomes has a unique banding pattern. Using the model of four chromatin types that reveals domains of varying compaction degrees, we were able to correlate the physical and cytological maps of some polytene chromosome regions and to show the main properties of genetic and molecular organization of bands and interbands, that we describe in this review. On the molecular map of the genome, the interbands correspond to decompacted aquamarine chromatin and 5' ends of ubiquitously active genes. Gray bands contain lazurite and malachite chromatin, intermediate in the level of compaction, and, mainly, coding parts of genes. Dense black transcriptionally inactive bands are enriched in ruby chromatin. Localization of several dozens of interbands on the genome molecular map allowed us to study in detail their architecture according to the data of whole genome projects. The distribution of proteins and regulatory elements of the genome in the promoter regions of genes localized in the interbands shows that these parts of interbands are probably responsible for the formation of open chromatin that is visualized in polytene chromosomes as interbands.Thus, the permanent genetic activity of interbands and gray bands and the inactivity of genes in black bands are the basis of the universal banding pattern in the chromosomes of all Drosophila tissues. The smallest fourth chromosome of Drosophila with an atypical protein composition of chromatin is a special case. Using the model of four chromatin states and fluorescent in situ hybridization, its cytological map was refined and the genomic coordinates of all bands and interbands were determined. It was shown that, in spite of the peculiarities of this chromosome, its band organization in general corresponds to the rest of the genome. Extremely long genes of different Drosophila chromosomes do not fit the common scheme, since they can occupy a series of alternating bands and interbands (up to nine chromosomal structures) formed by parts of these genes.

  • 169.
    Sjödin, Andreas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Öhrman, Caroline
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Bäckman, Stina
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Lärkeryd, Adrian
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Granberg, Malin
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Lundmark, Eva
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Karlsson, Edvin
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Nilsson, Elin
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Vallesi, Adriana
    cLaboratory of Eukaryotic Microbiology and Animal Biology, University of Camerino, Camerino, Macerata, Italy.
    Tellgren-Roth, Christian
    Uppsala Genome Center, National Genomics Infrastructure-Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, BMC, Uppsala, Sweden.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Thelaus, Johanna
    Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Complete Genome Sequence of Francisella endociliophora Strain FSC1006, Isolated from a Laboratory Culture of the Marine Ciliate Euplotes raikovi2014In: Genome Announcements, ISSN 2169-8287, E-ISSN 2169-8287, Vol. 2, no 6, p. 6 e01227-14-Article in journal (Refereed)
    Abstract [en]

    A strain of Francisella endociliophora was isolated from a laboratory culture of the marine ciliate Euplotes raikovi. Here, we report the complete genome sequence of the bacterial strain FSC1006 (Francisella Strain Collection, Swedish Defence Research Agency, Umeå, Sweden).

  • 170.
    Skottheim Honn, John
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Linn
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Rasmuson Lestander, Asa
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Regulation of twin of eyeless during Drosophila development2016In: Gene Expression Patterns, ISSN 1567-133X, E-ISSN 1872-7298, Vol. 20, no 2, p. 120-129Article in journal (Refereed)
    Abstract [en]

    The Pax-6 protein is vital for eye development in all seeing animals, from sea urchins to humans. Either of the Pax6 genes in Drosophila (twin of eyeless and eyeless) can induce a gene cascade leading to formation of entire eyes when expressed ectopically. The twin of eyeless (toy) gene in Drosophila is expressed in the anterior region of the early fly embryo. At later stages it is expressed in the brain, ventral nerve cord and (eventually) the visual primordium that gives rise to the eye-antennal imaginal discs of the larvae. These discs subsequently form the major part of the adult head, including compound eyes. We have searched for genes that are required for normal toy expression in the early embryo to elucidate initiating events of eye organogenesis. Candidate genes identified by mutation analyses were subjected to further knock-out and miss-expression tests to investigate their interactions with toy. Our results indicate that the head-specific gap gene empty spiracles can act as a repressor of Toy, while ocelliless (oc) and spalt major (salm) appear to act as positive regulators of toy gene expression. (C) 2016 Elsevier B.V. All rights reserved.

  • 171. Slane, Daniel
    et al.
    Kong, Jixiang
    Schmid, Markus
    Max Planck Institute for Developmental Biology, Department of Molecular Biology, Tübingen, Germany.
    Jürgens, Gerd
    Bayer, Martin
    Profiling of embryonic nuclear vs. cellular RNA in Arabidopsis thaliana2015In: Genomics Data, ISSN 1025-6059, E-ISSN 2213-5960, Vol. 4, p. 96-98Article in journal (Refereed)
    Abstract [en]

    In Arabidopsis, various cell type-specific whole-genome expression analyses have been conducted. However, the vast majority of these were performed with cellular RNA from root tissues or other easily accessible cell types [1]. Nuclear RNA was neglected for a long time as not being representative for transcriptomic studies. In recent years, however, there have been reports describing the validity of nuclear RNA for these types of studies [2] and [3]. Here we describe the generation, quality assessment and analysis of nuclear transcriptomic data from Arabidopsis embryos published by Slane et al. (2014) [4]. Comparison of nuclear with cellular gene expression demonstrated the usefulness of nuclear transcriptomics.

  • 172. Smouse, Peter E
    et al.
    Sork, Victoria L
    Scofield, Douglas G
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Grivet, Delphine
    Using seedling and pericarp tissues to determine maternal parentage of dispersed valley oak recruits2012In: Journal of Heredity, ISSN 0022-1503, E-ISSN 1465-7333, Vol. 103, no 2, p. 250-259Article in journal (Refereed)
    Abstract [en]

    The spatial pattern of established seedlings yields valuable information about variation in fecundity, dispersal, and spatial structure of distributed recruits, but separating maternal and paternal contributions in monoecious species has been hampered by the "2 parent'' problem. It is now possible to determine the maternal parentage of established recruits with genetic assay of maternally derived tissues of the seed or fruit, but the DNA of weathered maternal tissues often yields unreliable genotypes, reducing the practical range of such assay. We develop a mixed assay of seedling and seed (pericarp) tissues and illustrate it with distributed recruits of California valley oak (Quercus lobata Nee). Detailed analysis indicates correct maternal assignment rates of canopy patch recruits of 56% (seedling assay only) versus 94% (mixed assay). For open patch recruits, maternal assignment rates were less than 50% (seedling assay only) versus 91% (mixed assay). The strategy of choice is to use seedling genotypes to identify a small set of credible parental candidates and then deploy 3-4 well-chosen pericarp/endocarp loci to reduce that list to a single obvious maternal candidate. The increase in the number of recruits available for subsequent analysis is pronounced, increasing precision and statistical power for subsequent inference.

  • 173. Sniegula, Szymon
    et al.
    Johansson, Frank
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Nilsson-Örtman, Viktor
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Differentiation in developmental rate across geographic regions: a photoperiod driven latitude compensating mechanism?2012In: Oikos, ISSN 0030-1299, E-ISSN 1600-0706, Vol. 121, no 7, p. 1073-1082Article in journal (Refereed)
    Abstract [en]

    Genetic differentiation and phenotypic plasticity in growth rates along latitudinal gradients may benefit our understanding of latitudinal compensating mechanisms in life history patterns. Here we explore latitudinal compensatory growth mechanisms with respect to photoperiod in northern and southern populations of two damselfly species, Coenagrion puella and C. pulchellum. In addition we compared size of field-collected adults from southern and northern populations. Eggs from females in copulating tandems were collected at two or three localities for each species in each geographic region. Eggs were transported to the laboratory and the experiment started when the eggs hatched. The role of photoperiod on the expression of larval growth rate was evaluated under controlled laboratory conditions. Both species had lower growth rate when reared in the northern photoperiod, which is counter to expectations if species use photoperiodic cues to trigger compensatory growth. Instead, both species displayed countergradient variation in growth rates, which probably enable northern populations to compensate for the shorter growth season in the north. The smaller size of field-collected adults from northern populations also supports the view that these species compensate for the shorter growth season by investing in growth and development but accomplish this at the expense of decreased final size.

  • 174. Soler, Marçal
    et al.
    Plasencia, Anna
    Lepikson-Neto, Jorge
    Camargo, Eduardo L. O.
    Dupas, Annabelle
    Ladouce, Nathalie
    Pesquet, Edouard
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Mounet, Fabien
    Larbat, Romain
    Grima-Pettenati, Jacqueline
    The Woody-Preferential Gene EgMYB88 Regulates the Biosynthesis of Phenylpropanoid-Derived Compounds in Wood2016In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 7, article id 1422Article in journal (Refereed)
    Abstract [en]

    Comparative phylogenetic analyses of the R2R3-MYB transcription factor family revealed that five subgroups were preferentially found in woody species and were totally absent from Brassicaceae and monocots (Soler et al., 2015). Here, we analyzed one of these subgroups (WPS-I) for which no gene had been yet characterized. Most Eucalyptus members of WPS-I are preferentially expressed in the vascular cambium, the secondary meristem responsible for tree radial growth. We focused on EgMYB88, which is the most specifically and highly expressed in vascular tissues, and showed that it behaves as a transcriptional activator in yeast. Then, we functionally characterized EgMYB88 in both transgenic Arabidopsis and poplar plants overexpressing either the native or the dominant repression form (fused to the Ethylene-responsive element binding factor-associated Amphiphilic Repression motif, EAR). The transgenic Arabidopsis lines had no phenotype whereas the poplar lines overexpressing EgMYB88 exhibited a substantial increase in the levels of the flavonoid catechin and of some salicinoid phenolic glycosides (salicortin, salireposide, and tremulacin), in agreement with the increase of the transcript levels of landmark biosynthetic genes. A change in the lignin structure (increase in the syringyl vs. guaiacyl, S/G ratio) was also observed. Poplar lines overexpressing the EgMYB88 dominant repression form did not show a strict opposite phenotype. The level of catechin was reduced, but the levels of the salicinoid phenolic glycosides and the S/G ratio remained unchanged. In addition, they showed a reduction in soluble oligolignols containing sinapyl p-hydroxybenzoate accompanied by a mild reduction of the insoluble lignin content. Altogether, these results suggest that EgMYB88, and more largely members of the WPS-I group, could control in cambium and in the first layers of differentiating xylem the biosynthesis of some phenylpropanoid-derived secondary metabolites including lignin.

  • 175. Srivastava, Vaibhav
    et al.
    Obudulu, Ogonna
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University and Swedish University of Agricultural Sciences.
    Bygdell, Joakim
    Löfstedt, Tommy
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Nilsson, Robert
    Ahnlund, Maria
    Johansson, Annika
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Freyhult, Eva
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Computational life science cluster (CLiC), Umeå University.
    Qvarnström, Johanna
    Karlsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Melzer, Michael
    Moritz, Thomas
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Hvidsten, Torgeir R
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University and Department of Chemistry, Biotechnology; Food Science, Norwegian, University of Life Sciences, Ås Norwegian, Norway.
    Wingsle, Gunnar
    OnPLS integration of transcriptomic, proteomic and metabolomic data shows multi-level oxidative stress responses in the cambium of transgenic hipI- superoxide dismutase Populus plants2013In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 14, article id 893Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams.

    RESULTS: The main categories that appear to be significantly influenced in the transgenic plants were pathways related to redox regulation, carbon metabolism and protein degradation, e.g. the glycolysis and pentose phosphate pathways (PPP). The results provide system-level information on ROS metabolism and responses to oxidative stress, and indicate that some initial responses to oxidative stress may share common pathways.

    CONCLUSION: The proposed data evaluation strategy shows an efficient way of compiling complex, multi-platform datasets to obtain significant biological information.

  • 176.
    Stenberg, Per
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Lundberg, Lina E.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Anna-Mia
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Social Sciences, Department of Statistics.
    Svensson, Malin J.
    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).
    Buffering of segmental and chromosomal aneuploidies in Drosophila melanogaster2009In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 5, no 5Article in journal (Refereed)
    Abstract [en]

    Chromosomal instability, which involves the deletion and duplication of chromosomes or chromosome parts, is a common feature of cancers, and deficiency screens are commonly used to detect genes involved in various biological pathways. However, despite their importance, the effects of deficiencies, duplications, and chromosome losses on the regulation of whole chromosomes and large chromosome domains are largely unknown. Therefore, to explore these effects, we examined expression patterns of genes in several Drosophila deficiency hemizygotes and a duplication hemizygote using microarrays. The results indicate that genes expressed in deficiency hemizygotes are significantly buffered, and that the buffering effect is general rather than being mainly mediated by feedback regulation of individual genes. In addition, differentially expressed genes in haploid condition appear to be generally more strongly buffered than ubiquitously expressed genes in haploid condition, but, among genes present in triploid condition, ubiquitously expressed genes are generally more strongly buffered than differentially expressed genes. Furthermore, we show that the 4th chromosome is compensated in response to dose differences. Our results suggest general mechanisms have evolved that stimulate or repress gene expression of aneuploid regions as appropriate, and on the 4th chromosome of Drosophila this compensation is mediated by Painting of Fourth (POF).

  • 177. Szal, Bożena
    et al.
    Jastrzębska, Agata
    Kulka, Marek
    Leśniak, Karolina
    Podgórska, Anna
    Pärnik, Tiit
    Ivanova, Hiie
    Keerberg, Olav
    Gardeström, Per
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Rychter, Anna M
    Influence of mitochondrial genome rearrangement on cucumber leaf carbon and nitrogen metabolism2010In: Planta, ISSN 0032-0935, E-ISSN 1432-2048, Vol. 232, no 6, p. 1371-1382Article in journal (Refereed)
    Abstract [en]

    The MSC16 cucumber (Cucumis sativus L.) mitochondrial mutant was used to study the effect of mitochondrial dysfunction and disturbed subcellular redox state on leaf day/night carbon and nitrogen metabolism. We have shown that the mitochondrial dysfunction in MSC16 plants had no effect on photosynthetic CO(2) assimilation, but the concentration of soluble carbohydrates and starch was higher in leaves of MSC16 plants. Impaired mitochondrial respiratory chain activity was associated with the perturbation of mitochondrial TCA cycle manifested, e.g., by lowered decarboxylation rate. Mitochondrial dysfunction in MSC16 plants had different influence on leaf cell metabolism under dark or light conditions. In the dark, when the main mitochondrial function is the energy production, the altered activity of TCA cycle in mutated plants was connected with the accumulation of pyruvate and TCA cycle intermediates (citrate and 2-OG). In the light, when TCA activity is needed for synthesis of carbon skeletons required as the acceptors for NH(4) (+) assimilation, the concentration of pyruvate and TCA intermediates was tightly coupled with nitrate metabolism. Enhanced incorporation of ammonium group into amino acids structures in mutated plants has resulted in decreased concentration of organic acids and accumulation of Glu.

  • 178.
    Södergren, Agneta
    Umeå University, Faculty of Science and Technology.
    Frequency changes and equilibria in experimental populations of Drosophila melanogaster with three lethal carrying fourth chromosomes1979Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Populations where three different lethals are segregating as alleles have been analysed for the conditions of equilibrium and for the trends during elimination of one allele. Early and late selection as well as sexdependent and sexindependent selection has been taken into consideration.Cage populations of Drosophila melanogaster with different fourth chromosome lethals have been followed and compared to the theoretical model. When two marker chromosomes (ciDpol and spaCat) and one out of four recessive lethal chromosomes l(4)5, 1(4)8, 1(4)10 or l(4)14 were used, the same marker chromosome (ciDpol) became extinct in all populations. Early and late selective values which were obtained directly from the populations were compared to estimates of fitness components obtained in specially designed experiments of viability, developmental rate, mating ability and fecundity. When two out of the four recessive lethals and the marker chromosome, spaCat , were combined in new populations, all populations attained equilibrium withôut extinction. A correlation was found between the time of death of the lethal homozygotes and the equilibrium genotype frequencies. Overall selective values at equilibrium were estimated.

  • 179.
    Tan, Biyue
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Stora Enso AB.
    Genomic selection and genome-wide association studies to dissect quantitative traits in forest trees2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The convergence of quantitative genetics of complex traits with genomic technologies is quickly becoming an innovative approach to explore fundamental genetic questions and also have practical consequences for implementations in tree breeding. In this thesis, I used genomic selection and genome-wide association studies (GWAS) to dissect the genetic basis of quantitative traits, i.e. growth, phenology and wood property traits. I also assessed the importance of dominance and epistatic effects in hybrid Eucalyptus. Both dominance and epistasis are important in hybrids, as they are the likely contributing to the genetic basis of heterosis. To successfully implement genomic selection models, several important factors have to be considered. I found that for a good model establishment, both the size and composition of the training population, as well as the number of SNPs to be important considered. Based on the optimal models, additive, dominance and epistasis genetic effects of growth and wood traits have been estimated to evaluate genetic parameters and how these influence the prediction accuracy, which can be used in selecting elite breeding individuals or clones. I also addressed the advantage of genotyping-based analyses by showing that we could accurately correct pedigree information errors. More importantly, genotyping-based analyses capture both Mendelian segregation variation within full-sib families and cryptic genetic links through unknown common ancestors, which are not available from traditional pedigree data. GWAS were used to analyse growth and phenology related traits. Using a single-trait GWAS method, we identified a region strongly associated with the timing of bud set in Populus tremula, a trait with high heritability. For the growth related traits, we found that a multi-traits GWAS approach was more powerful than single-trait analyses as it identified more associated SNPs in hybrid Eucalyptus. Moreover, many more novel associated SNPs were identified from considering over-dominance effects in the GWAS analyses. After annotating the associated SNPs I show that these functional candidate genes were related to growth and responding to abiotic and biotic stress. In summary, the results of genomic selection and GWAS provided a deeper understanding of the genetic backgrounds of quantitative traits in forest trees.

  • 180.
    Tan, Biyue
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Biomaterials Division, Stora Enso AB, Nacka SE-13104, Sweden.
    Grattapaglia, Dario
    Martins, Gustavo Salgado
    Ferreira, Karina Zamprogno
    Sundberg, Björn
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Evaluating the accuracy of genomic prediction of growth and wood traits in two Eucalyptus species and their F-1 hybrids2017In: BMC Plant Biology, ISSN 1471-2229, E-ISSN 1471-2229, Vol. 17, article id 110Article in journal (Refereed)
    Abstract [en]

    Background: Genomic prediction is a genomics assisted breeding methodology that can increase genetic gains by accelerating the breeding cycle and potentially improving the accuracy of breeding values. In this study, we use 41,304 informative SNPs genotyped in a Eucalyptus breeding population involving 90 E. grandis and 78 E. urophylla parents and their 949 F-1 hybrids to develop genomic prediction models for eight phenotypic traits-basic density and pulp yield, circumference at breast height and height and tree volume scored at age three and six years. We assessed the impact of different genomic prediction methods, the composition and size of the training and validation set and the number and genomic location of SNPs on the predictive ability (PA). Results: Heritabilities estimated using the realized genomic relationship matrix (GRM) were considerably higher than estimates based on the expected pedigree, mainly due to inconsistencies in the expected pedigree that were readily corrected by the GRM. Moreover, the GRM more precisely capture Mendelian sampling among related individuals, such that the genetic covariance was based on the true proportion of the genome shared between individuals. PA improved considerably when increasing the size of the training set and by enhancing relatedness to the validation set. Prediction models trained on pure species parents could not predict well in F-1 hybrids, indicating that model training has to be carried out in hybrid populations if one is to predict in hybrid selection candidates. The different genomic prediction methods provided similar results for all traits, therefore either GBLUP or rrBLUP represents better compromises between computational time and prediction efficiency. Only slight improvement was observed in PA when more than 5000 SNPs were used for all traits. Using SNPs in intergenic regions provided slightly better PA than using SNPs sampled exclusively in genic regions. Conclusions: The size and composition of the training set and number of SNPs used are the two most important factors for model prediction, compared to the statistical methods and the genomic location of SNPs. Furthermore, training the prediction model based on pure parental species only provide limited ability to predict traits in interspecific hybrids. Our results provide additional promising perspectives for the implementation of genomic prediction in Eucalyptus breeding programs by the selection of interspecific hybrids.

  • 181.
    Tan, Biyue
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Biomaterials Division, Stora Enso AB, SE-131 04, Nacka, Sweden.
    Grattapaglia, Dario
    Wu, Harry X.
    Ingvarsson, Pär K.
    Genomic relationships reveal significant dominance effects for growth in hybrid Eucalyptus2018In: Plant Science, ISSN 0168-9452, E-ISSN 1873-2259, Vol. 267, p. 84-93Article in journal (Refereed)
    Abstract [en]

    Non-additive genetic effects can be effectively exploited in control-pollinated families with the availability of genome-wide markers. We used 41,304 SNP markers and compared pedigree vs. marker-based genetic models by analysing height, diameter, basic density and pulp yield for Eucalyptus urophylla x E.grandis control-pollinated families represented by 949 informative individuals. We evaluated models accounting for additive, dominance, and first-order epistatic interactions (additive by additive, dominance by dominance, and additive by dominance). We showed that the models can capture a large proportion of the genetic variance from dominance and epistasis for growth traits as those components are typically not independent. We also showed that we could partition genetic variances more precisely when using relationship matrices derived from markers compared to using only pedigree information. In addition, phenotypic prediction accuracies were only slightly increased by including dominance effects for growth traits since estimates of non-additive variances yielded rather high standard errors. This novel result improves our current understanding of the architecture of quantitative traits and recommends accounting for dominance variance when developing genomic selection strategies in hybrid Eucalyptus.

  • 182.
    Tan, Biyue
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Stora Enso AB.
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Biology, Swedish University of Agricultural Sciences.
    Multivariate genome-wide association identify loci for complex growth traits by considering additive and over-dominance effects in hybrid EucalyptusManuscript (preprint) (Other academic)
    Abstract [en]

    Genome-wide association studies are a powerful and widely used approach to decipher the genetic control of quantitative traits. One of the major challenges for traits in hybrid forest trees, such as hybrid Eucalyptus, is dissecting also non-additive effects for complex traits using a traditional linear mixed model. These non-additive effects, especially over-dominance effects, are one of most important hypotheses for the genetic basis of heterosis. In this study, we used a population including 949 F1 hybrids and their 174 parents, that were phenotyped for circumference at breast height and height at age of three years and six years, and also genotyped at 37,832 informative SNPs. Here we use and compare single-trait and multi-trait association models by accounting for additive and over-dominance effects, to evaluate genomic regions associated with the growth traits. For additive effect-based association model, nine significant SNPs were observed in multi-trait analyses, whereas only two unique SNPs were detected in single-trait analyses. These two SNPs were also identified in the multi-trait model. When evaluating over-dominance effects, 17 and 13 SNPs were identified from multi-trait and single-trait models, respectively. Moreover, more phenotypic variation can be explained by SNPs identified from multi-trait GWAS when including over-dominance effects. Overall, this study shows the added values of including over-dominance and considering multiple traits for identifying genomic regions that control traits of interest and that could contribute to heterosis in hybrids.

  • 183.
    Terebieniec, Barbara
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Using systems genetics to explore the complexity of leaf shape variation in Populus tremula2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Leaves are essential for sustaining humanity as they function as the energy and oxygen-producing organ of plants. Intensive research on physiological processes has contributed immensely to our understanding of the function of leaves. However, comparatively little is known about how leaf size and shape is determined. The aim of my PhD was to assay leaf shape variation among individuals of Populus tremula (European aspen) sampled across the distribution range of Sweden to characterize the genetic architecture underlying variation, including elucidating contributing molecular mechanisms.

    In this PhD I employed an integrated systems genetics and systems biology approach to identify genetic components of variation and to assign biological function to these. We integrated population-wide data on leaf shape, gene expression and genome variation from a collection of P. tremula genotypes and used this to perform genome-wide association studies. We then integrated these results with a systems biology transcriptomics study of leaf development to provide developmental and biological context. We demonstrate that our developmental gene expression series captured known homologs of functionally characterized Arabidopsis thaliana genes and biological processes of importance during leaf development. In addition to these known genes of high importance, we also identified many novel candidate genes. Our systems genetics approach identified numerous genes with a potential role in leaf development that was supported by the developmental time series. From our association studies and population analyses we have shown that there are no large-effect loci contributing to variation in leaf shape and that highly ranked loci associated with leaf shape are primarily located in the regulatory regions of genes. Furthermore, we identified loci controlling variation in gene expression and sets of genes with significant differential expression between groups of genotypes with highly contrasting leaf shapes. We show that genes with significant associations influencing expression among genotypes are enriched in the periphery of the corresponding gene co-expression network and that they experience relaxed selective constraint. Taken together, these results suggest that leaf shape is a highly complex trait controlled by a large number of loci, each contributing only a small effect, that those loci likely act via modulation of gene expression and that they do not show signals of adaptive selection. In addition, we adapted and optimized the method of spatial transcriptomics for use in plant species. This method provides a transcriptome-wide in situ, spatially-resolved assay of transcript expression at high spatial resolution.

  • 184. Tiukova, Ievgeniia A.
    et al.
    Pita, Will de Barros
    Sundell, David
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Momeni, Majid Haddad
    Horn, Svein Jarle
    Stahlberg, Jerry
    de Morais, Marcos Antonio, Jr.
    Passoth, Volkmar
    Adaptation of Dekkera bruxellensis to lignocellulose-based substrate2014In: Biotechnology and applied biochemistry, ISSN 0885-4513, E-ISSN 1470-8744, Vol. 61, no 1, p. 51-57Article in journal (Refereed)
    Abstract [en]

    Adaptation of Dekkera bruxellensis to lignocellulose hydrolysate was investigated. Cells of D. bruxellensis were grown for 72 and 192H in batch and continuous culture, respectively (adapted cells). Cultivations in semisynthetic medium were run as controls (nonadapted cells). To test the adaptation, cells from these cultures were reinoculated in the lignocellulose medium, and growth and ethanol production characteristics were monitored. Cells adapted to lignocellulose hydrolysate had a shorter lag phase, grew faster, and produced a higher ethanol concentration as compared with nonadapted cells. A stability test showed that after cultivation in rich medium, cells partially lost the adapted phenotype but still showed faster growth and higher ethanol production as compared with nonadapted cells. Because alcohol dehydrogenase genes have been described to be involved in the adaptation to furfural in Saccharomyces cerevisiae, an analogous mechanism of adaptation to lignocelluloses hydrolysate of D. bruxellensis was hypothesized. However, gene expression analysis showed that genes homologous to S. cerevisiae ADH1 were not involved in the adaptation to lignocelluloses hydrolysate in D. bruxellensis.

  • 185. Tuskan, Gerald A.
    et al.
    DiFazio, Steve
    Faivre-Rampant, Patricia
    Gaudet, Muriel
    Harfouche, Antoine
    Jorge, Veronique
    Labbe, Jessy L.
    Ranjan, Priya
    Sabatti, Maurizio
    Slavov, Gancho
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Tschaplinski, Timothy J.
    Yin, Tongming
    The obscure events contributing to the evolution of an incipient sex chromosome in Populus: a retrospective working hypothesis2012In: Tree Genetics & Genomes, ISSN 1614-2942, E-ISSN 1614-2950, Vol. 8, no 3, p. 559-571Article, review/survey (Refereed)
    Abstract [en]

    Genetic determination of gender is a fundamental developmental and evolutionary process in plants. Although it appears that dioecy in Populus is genetically controlled, the precise gender-determining systems remain unclear. The recently released second draft assembly and annotated gene set of the Populus genome provided an opportunity to revisit this topic. We hypothesized that over evolutionary time, selective pressure has reformed the genome structure and gene composition in the peritelomeric region of the chromosome XIX, which has resulted in a distinctive genome structure and cluster of genes contributing to gender determination in Populus trichocarpa. Multiple lines of evidence support this working hypothesis. First, the peritelomeric region of the chromosome XIX contains significantly fewer single nucleotide polymorphisms than the rest of Populus genome and has a distinct evolutionary history. Second, the peritelomeric end of chromosome XIX contains the largest cluster of the nucleotide-binding site-leucine-rich repeat (NBS-LRR) class of disease resistance genes in the entire Populus genome. Third, there is a high occurrence of small microRNAs on chromosome XIX, which is coincident to the region containing the putative gender-determining locus and the major cluster of NBS-LRR genes. Further, by analyzing the metabolomic profiles of floral bud in male and female Populus trees using a gas chromatography-mass spectrometry, we found that there are gender-specific accumulations of phenolic glycosides. Taken together, these findings led to the hypothesis that resistance to and regulation of a floral pathogen and gender determination coevolved, and that these events triggered the emergence of a nascent sex chromosome. Further studies of chromosome XIX will provide new insights into the genetic control of gender determination in Populus.

  • 186. Tylewicz, S.
    et al.
    Petterle, A.
    Marttila, S.
    Miskolczi, P.
    Azeez, A.
    Singh, R. K.
    Immanen, J.
    Mähler, Niklas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Hvidsten, Torgerir R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Eklund, D. M.
    Bowman, J. L.
    Helariutta, Y.
    Bhalerao, R. P.
    Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication2018In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 360, no 6385, p. 212-214Article in journal (Refereed)
    Abstract [en]

    In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals.

  • 187.
    Tükenmez, Hasan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Influence of wobble uridine modifications on eukaryotic translation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Elongator is a conserved six subunit protein (Elp1p-Elp6p) complex that is required for the formation of ncm5 and mcm5 side chains at wobble uridines in transfer RNAs (tRNAs). Moreover, loss-of-function mutations in any gene encoding an Elongator subunit results in translational defects and a multitude of phenotypic effects. This thesis is based on investigations of effects of wobble uridine modifications on translation.

    In Saccharomyces cerevisiae, ncm5U34-, mcm5U34- and mcm5s2U34- modified wobble nucleosides in tRNAs are important for proper codonanticodon interactions. My colleagues and I (hereafter we) showed that mcm5 and s2 groups at wobble uridine in tRNAs are vital for maintaining the reading frame during translation, as absence of these modifications increases the frequency of +1 frameshifting. We also showed that +1 frameshifting events at lysine AAA codons in Elongator mutants are due to slow entry of the hypomodified tRNA Lyss2UUU to the ribosomal A-site.

    Ixr1p is a protein that plays a key role in increasing production of deoxynucleotides (dNTPs) in responses to DNA damage, via induction of Ribonucleotide reductase 1 (Rnr1p), in S. cerevisiae. We showed that expression of Ixr1p is reduced in elp3Δ mutants due to a post-transcriptional defect, which results in lower levels of Rnr1p in responses to DNA damage. Collectively, these results suggest that high sensitivity of Elongator mutants to DNA damaging agents might be partially due to reductions in Ixr1p expression and hence Rnr1p levels.

    Elongator mutant phenotypes are linked to several cellular processes. To probe the mechanisms involved we investigated the metabolic perturbations associated with absence of a functional ELP3 gene in S. cerevisiae. We found that its absence results in widespread metabolic perturbations under both optimal (30°C) and semi-permissive (34°C) growth conditions. We also found that changes in levels of certain metabolites (but not others) were ameliorated by elevated levels of hypomodified tRNAs, suggesting that amelioration of perturbations of these metabolites might be sufficient for suppression of the Elongator mutant phenotypes.

    A mutation in the IKBKAP (hELP1) gene results in lower levels of the full-length hELP1 protein, which causes a neurodegenerative disease in humans called familial dysautonomia (FD). We showed that the levels of mcm5s2U-modified wobble nucleoside in tRNAs are lower in both brain tissues and fibroblast cell lines derived from FD patients than in corresponding materials derived from healthy individuals. This suggests that FD may result from inefficient translation due to partial loss of mcm5s2U-modified nucleosides in tRNAs.

  • 188.
    Tükenmez, Hasan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Karlsborn, Tony
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Mahmud, A K M Firoj
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Chen, Changchun
    Xu, Fu
    Byström, Anders S.
    Elongator complex enhances Rnr1p levels in response to DNA damage by influencing Ixr1p expressionManuscript (preprint) (Other academic)
  • 189. Van Aken, Olivier
    et al.
    De Clercq, Inge
    Ivanova, Aneta
    Law, Simon R
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Van Breusegem, Frank
    Millar, A. Harvey
    Whelan, James
    Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases2016In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 171, no 3, p. 2150-2165Article in journal (Refereed)
    Abstract [en]

    Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control.

  • 190. Varadharajan, Srinidhi
    et al.
    Sandve, Simen R.
    Gillard, Gareth B.
    Tørresen, Ole K.
    Mulugeta, Teshome D.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lien, Sigbjørn
    Vøllestad, Leif Asbjørn
    Jentoft, Sissel
    Nederbragt, Alexander J.
    Jakobsen, Kjetill S.
    The Grayling Genome Reveals Selection on Gene Expression Regulation after Whole-Genome Duplication2018In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 10, no 10, p. 2785-2800Article in journal (Refereed)
    Abstract [en]

    Whole-genome duplication (WGD) has been a major evolutionary driver of increased genomic complexity in vertebrates. One such event occurred in the salmonid family ∼80 Ma (Ss4R) giving rise to a plethora of structural and regulatory duplicate-driven divergence, making salmonids an exemplary system to investigate the evolutionary consequences of WGD. Here, we present a draft genome assembly of European grayling (Thymallus thymallus) and use this in a comparative framework to study evolution of gene regulation following WGD. Among the Ss4R duplicates identified in European grayling and Atlantic salmon (Salmo salar), one-third reflect nonneutral tissue expression evolution, with strong purifying selection, maintained over ∼50 Myr. Of these, the majority reflect conserved tissue regulation under strong selective constraints related to brain and neural-related functions, as well as higher-order protein–protein interactions. A small subset of the duplicates have evolved tissue regulatory expression divergence in a common ancestor, which have been subsequently conserved in both lineages, suggestive of adaptive divergence following WGD. These candidates for adaptive tissue expression divergence have elevated rates of protein coding- and promoter-sequence evolution and are enriched for immune- and lipid metabolism ontology terms. Lastly, lineage-specific duplicate divergence points toward underlying differences in adaptive pressures on expression regulation in the nonanadromous grayling versus the anadromous Atlantic salmon. Our findings enhance our understanding of the role of WGD in genome evolution and highlight cases of regulatory divergence of Ss4R duplicates, possibly related to a niche shift in early salmonid evolution.

  • 191.
    von Hofsten, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Olsson, Per-Erik
    Zebrafish sex determination and differentiation: involvement of FTZ-F1 genes2005In: Reproductive Biology and Endocrinology, ISSN 1477-7827, E-ISSN 1477-7827, Vol. 3, article id 63Article, review/survey (Refereed)
    Abstract [en]

    Sex determination is the process deciding the sex of a developing embryo. This is usually determined genetically; however it is a delicate process, which in many cases can be influenced by environmental factors. The mechanisms controlling zebrafish sex determination and differentiation are not known. To date no sex linked genes have been identified in zebrafish and no sex chromosomes have been identified. However, a number of genes, as presented here, have been linked to the process of sex determination or differentiation in zebrafish. The zebrafish FTZ-F1 genes are of central interest as they are involved in regulating interrenal development and thereby steroid biosynthesis, as well as that they show expression patterns congruent with reproductive tissue differentiation and function. Zebrafish can be sex reversed by exposure to estrogens, suggesting that the estrogen levels are crucial during sex differentiation. The Cyp19 gene product aromatase converts testosterone into 17 beta-estradiol, and when inhibited leads to male to female sex reversal. FTZ-F1 genes are strongly linked to steroid biosynthesis and the regulatory region of Cyp19 contains binding sites for FTZ-F1 genes, further linking FTZ-F1 to this process. The role of FTZ-1 and other candidates for zebrafish sex determination and differentiation is in focus of this review.

  • 192. Wallace, Stephanie E.
    et al.
    Regalado, Ellen S.
    Gong, Limin
    Janda, Alexandra L.
    Guo, Dong-chuan
    Russo, Claudio F.
    Kulmacz, Richard J.
    Hanna, Nadine
    Jondeau, Guillaume
    Boileau, Catherine
    Arnaud, Pauline
    Lee, Kwanghyuk
    Leal, Suzanne M.
    Hannuksela, Matias
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johnston, Tami
    Antolik, Christian
    Hostetler, Ellen M.
    Colombo, Roberto
    Milewicz, Dianna M.
    MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants2019In: Genetics in Medicine, ISSN 1098-3600, E-ISSN 1530-0366, Vol. 21, no 1, p. 144-151Article in journal (Refereed)
    Abstract [en]

    Purpose: Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLKmissense variants are pathogenic and information to guide aortic disease management are limited.

    Methods: Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed.

    Results: Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK.

    Conclusion: These data further define the aortic phenotype associated with MYLKpathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.

  • 193.
    Wang, B.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Climent, J.
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Horizontal gene transfer from a flowering plant to the insular pine Pinus canariensis (Chr. Sm. Ex DC in Buch)2015In: Heredity, ISSN 0018-067X, E-ISSN 1365-2540, Vol. 114, no 4, p. 413-418Article in journal (Refereed)
    Abstract [en]

    Horizontal gene transfer (HGT) is viewed as very common in the plant mitochondrial (mt) genome, but, to date, only one case of HGT has been found in gymnosperms. Here we report a new case of HGT, in which a mt nad5-1 fragment was transferred from an angiosperm to Pinus canariensis. Quantitative assay and sequence analyses showed that the foreign nad5-1 is located in the mt genome of P. canariensis and is nonfunctional. An extensive survey in the genus Pinus revealed that the angiosperm-derived nad5-1 is restricted to P. canariensis and present across the species' range. Molecular dating based on chloroplast DNA suggested that the HGT event occurred in the late Miocene after P. canariensis split from its closest relatives, and that the foreign copy became fixed in P. canariensis owing to drift during its colonization of the Canary Islands. The mechanism of this HGT is unclear but it was probably achieved through either direct cell-cell contact or external vectors. Our discovery provides evidence for an important role of HGT in plant mt genome evolution.

  • 194.
    Wang, Baosheng
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Mahani, Marjan Khalili
    Ng, Wei Lun
    Kusumi, Junko
    Phi, Hai Hong
    Inomata, Nobuyuki
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Szmidt, Alfred E.
    Extremely low nucleotide polymorphism in Pinus krempfii Lecomte, a unique flat needle pine endemic to Vietnam2014In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 4, no 11, p. 2228-2238Article in journal (Refereed)
    Abstract [en]

    Pinus krempfii Lecomte is a morphologically and ecologically unique pine, endemic to Vietnam. It is regarded as vulnerable species with distribution limited to just two provinces: Khanh Hoa and Lam Dong. Although a few phylogenetic studies have included this species, almost nothing is known about its genetic features. In particular, there are no studies addressing the levels and patterns of genetic variation in natural populations of P.krempfii. In this study, we sampled 57 individuals from six natural populations of P.krempfii and analyzed their sequence variation in ten nuclear gene regions (approximately 9kb) and 14 mitochondrial (mt) DNA regions (approximately 10kb). We also analyzed variation at seven chloroplast (cp) microsatellite (SSR) loci. We found very low haplotype and nucleotide diversity at nuclear loci compared with other pine species. Furthermore, all investigated populations were monomorphic across all mitochondrial DNA (mtDNA) regions included in our study, which are polymorphic in other pine species. Population differentiation at nuclear loci was low (5.2%) but significant. However, structure analysis of nuclear loci did not detect genetically differentiated groups of populations. Approximate Bayesian computation (ABC) using nuclear sequence data and mismatch distribution analysis for cpSSR loci suggested recent expansion of the species. The implications of these findings for the management and conservation of P.krempfii genetic resources were discussed.

  • 195.
    Wang, Baosheng
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Mitochondrial DNA capture and divergence in Pinus provide new insights into the evolution of the genus2014In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 80, p. 20-30Article in journal (Refereed)
    Abstract [en]

    The evolution of the mitochondrial (mt) genome is far from being fully understood. Systematic investigations into the modes of inheritance, rates and patterns of recombination, nucleotide substitution, and structural changes in the mt genome are still lacking in many groups of plants. In this study, we sequenced >11 kbp mtDNA segments from multiple accessions of 36 pine species to characterize the evolutionary patterns of mtDNA in the genus Pious. We found extremely low substitution rates and complex repetitive sequences scattered across different genome regions, as well as chimeric structures that were probably generated by multiple intergenomic recombinations. The mtDNA-based phylogeny of the genus differed from that based on chloroplast and nuclear DNA in the placement of several groups of species. Such discordances suggest a series of mtDNA capture events during past range shifts of the pine species and that both vertical and horizontal inheritance are implicated in the evolution of mtDNA in Pinus. MtDNA dating revealed that most extant lineages of the genus originated during Oligocene-Miocene radiation and subgenus Strobus diversified earlier than subgenus Pinus. Our findings illustrate a reticular evolutionary pathway for the mt genome through capture and recombination in the genus Pinus, and provide new insights into the evolution of the genus.

  • 196.
    Wang, Jing
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Faculty of Life Sciences, Norwegian University of Life Sciences, Ås, Norway.
    Ding, Jihua
    Tan, Biyue
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Stora Enso Biomaterials, 13104 Nacka, Sweden.
    Robinson, Kathryn M
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Michelson, Ingrid H.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Johansson, Anna
    Nystedt, Bjorn
    Scofield, Douglas
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Ecology and Genetics, Evolutionary Biology, Uppsala University, Uppsala, Sweden; Uppsala Multidisciplinary Center for Advanced Computational Science, Uppsala University, Uppsala, Sweden.
    Nilsson, Ove
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Street, Nathaniel R.
    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.
    A major locus controls local adaptation and adaptive life history variation in a perennial plant2018In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 19, article id 72Article in journal (Refereed)
    Abstract [en]

    Background: The initiation of growth cessation and dormancy represent critical life history trade offs between survival and growth and have important fitness effects in perennial plants Such adaptive life history traits often show strong local adaptation along environmental gradients but, despite then importance, the genetic architecture of these traits remains poorly understood.

    Results: We integrate whole genome re sequencing with environmental and phenotypic data from common garden experiments to investigate the genomic basis of local adaptation across a latitudinal gradient in European aspen (Populus tremula). A single genomic region containing the PtFT2 gene mediates local adaptation in the timing of bud set and explains 65% of the observed genetic variation in bud set This locus is the likely target of a recent selective sweep that originated right before or during colonization of northern Scandinavia following the last glaciation Field and greenhouse experiments confirm that variation in PtFT2 gene expression affects the phenotypic variation in bud set that we observe in wild natural populations.

    Conclusions: Our results reveal a major effect locus that determines the timing of bud set and that has facilitated rapid adaptation to shorter growing seasons and colder climates in European aspen. The discovery of a single locus explaining a substantial fraction of the variation in a key life-history trait is remarkable, given that such traits are generally considered to be highly polygenic. These findings provide a dramatic illustration of how loci of large effect for adaptive traits can arise and be maintained over large geographical scales in natural populations.

  • 197.
    Wang, Jing
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    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.
    Scofield, Douglas
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Ecology and Genetics: Evolutionary Biology, Uppsala University, Uppsala; Uppsala Multidisciplinary Center for Advanced Computational Science, Uppsala University, Uppsala .
    Ingvarsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Natural Selection and Recombination Rate Variation Shape Nucleotide Polymorphism Across the Genomes of Three Related Populus Species2016In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 202, no 3, p. 1185-1200Article in journal (Refereed)
    Abstract [en]

    A central aim of evolutionary genomics is to identify the relative roles that various evolutionary forces have played in generating and shaping genetic variation within and among species. Here we use whole-genome resequencing data to characterize and compare genome-wide patterns of nucleotide polymorphism, site frequency spectrum, and population-scaled recombination rates in three species of PopulusPopulus tremulaP. tremuloides, and P. trichocarpa. We find that P. tremuloides has the highest level of genome-wide variation, skewed allele frequencies, and population-scaled recombination rates, whereas P. trichocarpa harbors the lowest. Our findings highlight multiple lines of evidence suggesting that natural selection, due to both purifying and positive selection, has widely shaped patterns of nucleotide polymorphism at linked neutral sites in all three species. Differences in effective population sizes and rates of recombination largely explain the disparate magnitudes and signatures of linked selection that we observe among species. The present work provides the first phylogenetic comparative study on a genome-wide scale in forest trees. This information will also improve our ability to understand how various evolutionary forces have interacted to influence genome evolution among related species.

  • 198.
    Wang, Jing
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Tan, Biyue
    Street, Nathaniel
    Scofield, Douglas
    Ingvarsson, Pär
    The signatures of local adaptation at the genomic level in European aspen (Populus tremula)Manuscript (preprint) (Other academic)
    Abstract [en]

    Although local adaptation plays a fundamental role in maintaining adaptive genetic variation as a response to changing environments, its underlying genetic mechanisms remains poorly understood. In this study, we integrate “top-down” and “bottom-up” approaches to search for genomic signatures of local adaptation in Populus tremula along a latitudinal gradient across Sweden. We find that a majority of single nucleotide polymorphisms (SNPs) (~95%) identified as being involved in local adaptation are tightly clustered in a single genomic region on chromosome 10. This region harbors the candidate gene FLOWERING LOCUS T2 (FT2) that has long been known to play important roles in the regulation of growth cessation and dormancy induction in perennial plants. Our results provide empirical evidence suggesting that in the context of high rates of gene flow, the genomic architecture of local adaptation tends to enrich for few large-effect and/or tightly clustered loci rather than many independent loci of small effect. The signatures of selection at the candidate region are mostly consistent with soft selective sweeps, where different adaptive haplotypes originating from standing genetic variation sweep to high frequency in different latitudinal regions. In particular, we identify a recent and strong selective sweep that is regionally restricted to the northernmost populations. This indicates that high-latitude populations likely have undergone a stronger adaptive response to the greater environmental perturbation during the post-glacial colonization of northern Scandinavia.

  • 199.
    Wang, Wei-Zhou
    et al.
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China; Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Guo, Xiong
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Duan, Chen
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Ma, Wei Juan
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Y G
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Xu, P
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Gao, Z Q
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Wang, Z F
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Yan, H
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Zhang, Y F
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Yu, Y X
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Chen, J C
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Comparative analysis of gene expression profiles between the normal human cartilage and the one with endemic osteoarthritis.2009In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 17, no 1, p. 83-90, article id 18579416Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the differences in gene expression profiles of adult articular cartilage with endemic osteoarthritis (OA), Kashin-Beck disease (KBD), and the same regions in the normal joint.

    METHODS: The messenger RNA expression profiles of articular cartilage with KBD diagnosed according to "Diagnosing Criteria of Kashin-Beck Disease in China" were compared with the normal cartilage. Total RNA isolated separately from four pairs of the KBD and normal cartilage samples were evaluated by oligonucleotide microarray analysis. The microarray data were confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) amplification and were compared with previously published experiments.

    RESULTS: About 4100 transcripts, which corresponded to 35% of the expressed transcripts, showed >or=twofold differences in expression between the cartilage tissues in pairs. Approximately 2% of the expressed genes (79, 55 genes expressed in KBD>normal; 24 genes expressed in KBD<normal) were commonly expressed in the four pairs of samples. The expression of some genes related to the metabolism, apoptosis, cell proliferation and matrix degradation activity was significantly different in KBD cartilage than in the normal, similar to the findings for genes that inhibit matrix degradation. Comparisons of qRT-PCR data and the previously reported data with the result of gene chips support the validity of our microarray data.

    CONCLUSION: Differences between KBD cartilage and the normal exhibited a similar pattern among the four pairs examined, indicating the presence of common mechanisms mainly including chondrocyte metabolism and apoptosis that contribute to cartilage destruction in KBD.

  • 200. Wedin, Mats
    et al.
    Wiklund, Elisabeth
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Jorgensen, Per Magnus
    Ekman, Stefan
    Slippery when wet: phylogeny and character evolution in the gelatinous cyanobacterial lichens (Peltigerales, Ascomycetes)2009In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 53, no 3, p. 862-871Article in journal (Refereed)
    Abstract [en]

    Many lichen fungi form symbioses with filamentous Nostoc cyanobacteria, which cause the lichen to swell and become extremely gelatinous when moist. Within the Lecanoromycetes, such gelatinous lichens are today mainly classified in the Collemataceae (Peltigerales, Ascomycota). We performed Bayesian MCMC, maximum likelihood, and maximum parsimony analyses of three independent markers (mtSSU rDNA, nuLSU rDNA, and RPB1), to improve our understanding of the phylogeny and classification in the Peltigerales, as well as the evolution of morphological characters that have been used for classification purposes in this group. The Collemataceae and the non-gelatinous Parmariaceae are paraphyletic but can be re-circumscribed as monophyletic if Leciophysma, Physma, Ramalodium and Staurolemma are transferred to the Parmariaceae. The gelatinous taxa transferred to the Parmariaceae deviate from other Collemataceae in having simple ascospores, and several also have a ring-shaped exciple as in other Pannariaceae, rather than the disc-shaped exciple found in the typical Collemataceae. Both Collema and Leptogium are non-monophyletic. The re-circumscribed Collemataceae shares a distinct ascus type with the sister group Placynthiaceae and the Coccocarpiaceae, whereas Parmariaceae includes a variety of structures. All Parmariaceae have one-celled ascospores, whereas all Collemataceae have two- or multi-celled spores. Reconstructions of the number of character state transformations in exciple structure, thallus gelatinosity, and ascus apex structure indicate that the number of transformations is distinctly higher than the minimum possible. Most state transformations in the exciple took place from a ring-shaped to a disc-shaped exciple. Depending on the reconstruction method, most or all transformations in thallus structure took place from a non-gelatinous to a gelatinous thallus. Gains and losses of internal structures in the ascus apex account for all or a vast majority of the number of transformations in the ascus, whereas direct transformations between asci with internal structures appear to have been rare.

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