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  • 1051.
    Uebbing, Severin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Bolivar, Paulina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Burri, Reto
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ludovic, Dutoit
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Divergence in gene expression within and between two closely related flycatcher speciesManuscript (preprint) (Other academic)
    Abstract [en]

    Compared to DNA sequence evolution, relatively little is known about the character of gene expression evolution as species diverge. For example, it is unclear if gene expression generally evolves in a clock-like manner (by stabilizing selection or from neutral evolution) or if there are frequent episodes of directional selection. To gain insights into the evolutionary divergence of gene expression patterns, we sequenced and compared the transcriptomes of multiple tissues from population samples of collared (Ficedula albicollis) and pied flycatchers (F. hypoleuca), a species pair which diverged less than one million years ago. Tissues resolved into separate clusters in non-metric multidimensional scaling ordination analysis and samples from the two species generally clustered by tissue rather than by species. Tissues differed in the degrees of expression variance within species and divergence between species. Variance was positively correlated with expression breadth and negatively correlated with protein interactivity, suggesting that pleiotropic constraints reduce gene expression variance within species. Variance was correlated with between-species divergence, consistent with a pattern expected from stabilizing selection and neutral evolution. Using an expression QST approach, we identified genes differentially expressed between species. We also identified 10 genes uniquely expressed in one of the species. For one such gene (DPP7, uniquely expressed in collared flycatcher), the absence of expression in pied flycatchers could be associated with a fixed ≈ 20 kb deletion including 11 out of 13 exons in this species. This study conducted in a young vertebrate speciation model system expands our knowledge of how gene expression evolves in natural populations.

  • 1052.
    Uebbing, Severin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Konzer, Anne
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Xu, Luohao
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Quantitative Mass Spectrometry Reveals Partial Translational Regulation for Dosage Compensation in Chicken2015In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 32, no 10, p. 2716-2725Article in journal (Refereed)
    Abstract [en]

    There is increasing evidence that dosage compensation is not a ubiquitous feature following sex chromosome evolution, especially not in organisms where females are the heterogametic sex, like in birds. Even when it occurs, compensation can be incomplete and limited to dosage-sensitive genes. However, previous work has mainly studied transcriptional regulation of sex-linked genes, which may not reflect expression at the protein level. Here, we used liquid chromatography–tandem mass spectrometry to detect and quantify expressed levels of more than 2,400 proteins in ten different tissues of male and female chicken embryos. For comparison, transcriptome sequencing was performed in the same individuals, five of each sex. The proteomic analysis revealed that dosage compensation was incomplete, with a mean male-to-female (M:F) expression ratio of Z-linked genes of 1.32 across tissues, similar to that at the RNA level (1.29). The mean Z chromosome-to-autosome expression ratio was close to 1 in males and lower than 1 in females, consistent with partly reduced Z chromosome expression in females. Although our results exclude a general mechanism for chromosome-wide dosage compensation at translation, 30% of all proteins encoded from Z-linked genes showed a significant change in the M:F ratio compared with the corresponding ratio at the RNA level. This resulted in a pattern where some genes showed balanced expression between sexes and some close to 2-fold higher expression in males. This suggests that proteomic analyses will be necessary to reveal a more complete picture of gene regulation and sex chromosome evolution.

  • 1053. Urioste, J I
    et al.
    Franzén, Jessica
    Stockholm University, Faculty of Social Sciences, Department of Statistics.
    Windig, J J
    Strandberg, E
    Genetic variability of alternative somatic cell count traits and their relationship with clinical and subclinical mastitis2011In: Interbull Bulletin, ISSN 1011-6079, no 44, p. 204-209Article in journal (Refereed)
  • 1054. Valanne, Susanna
    et al.
    Myllymäki, Henna
    Kallio, Jenni
    Schmid, Martin Rudolf
    Kleino, Anni
    Murumägi, Astrid
    Airaksinen, Laura
    Kotipelto, Tapio
    Kaustio, Meri
    Ulvila, Johanna
    Esfahani, Shiva Seyedoleslami
    Engström, Ylva
    Silvennoinen, Olli
    Hultmark, Dan
    Parikka, Mataleena
    Rämet, Mika
    Genome-wide RNA interference in Drosophila cells identifies G protein-coupled receptor kinase 2 as a conserved regulator of NF-kappaB signaling.2010In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 184, no 11Article in journal (Refereed)
    Abstract [en]

    Because NF-kappaB signaling pathways are highly conserved in evolution, the fruit fly Drosophila melanogaster provides a good model to study these cascades. We carried out an RNA interference (RNAi)-based genome-wide in vitro reporter assay screen in Drosophila for components of NF-kappaB pathways. We analyzed 16,025 dsRNA-treatments and identified 10 novel NF-kappaB regulators. Of these, nine dsRNA-treatments affect primarily the Toll pathway. G protein-coupled receptor kinase (Gprk)2, CG15737/Toll pathway activation mediating protein, and u-shaped were required for normal Drosomycin response in vivo. Interaction studies revealed that Gprk2 interacts with the Drosophila IkappaB homolog Cactus, but is not required in Cactus degradation, indicating a novel mechanism for NF-kappaB regulation. Morpholino silencing of the zebrafish ortholog of Gprk2 in fish embryos caused impaired cytokine expression after Escherichia coli infection, indicating a conserved role in NF-kappaB signaling. Moreover, small interfering RNA silencing of the human ortholog GRK5 in HeLa cells impaired NF-kappaB reporter activity. Gprk2 RNAi flies are susceptible to infection with Enterococcus faecalis and Gprk2 RNAi rescues Toll(10b)-induced blood cell activation in Drosophila larvae in vivo. We conclude that Gprk2/GRK5 has an evolutionarily conserved role in regulating NF-kappaB signaling.

  • 1055. Valdiosera, Cristina
    et al.
    García, Nuria
    Dalén, Love
    Stockholm University, Faculty of Science, Department of Zoology. Zoologisk ekologi.
    Smith, Colin
    Kahlke, Ralf-Dietrich
    Lidén, Kerstin
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies. Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies, Archaeological Research Laboratory. Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Angerbjörn, Anders
    Stockholm University, Faculty of Science, Department of Zoology. Zoologisk ekologi.
    Arsuaga, Juan Luis
    Götherström, Anders
    Uppsala universitet.
    Typing single polymorphic nucleotides in mitochondrial DNA as a way to access Middle Pleistocene DNA.2006In: Biol Lett, ISSN 1744-9561, Vol. 2, no 4, p. 601-3Article in journal (Refereed)
  • 1056. 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.

  • 1057.
    Vanhala, Tytti
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Normann, Kjersti R.
    Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway.
    Lundström, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Weller, James L.
    School of Biological Sciences, University of Tasmania, Hobart, TAS 7001, Australia..
    Leino, Matti
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Nordiska museet - Swedish Museum of Cultural History, SE-643 98, Julita, Sweden.
    Hagenblad, Jenny
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Norwegian University of Science and Technology, Trondheim, Norway.
    Flowering time adaption in Swedish landrace pea (Pisum sativum L.)2016In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 17, no 1, p. 117-Article in journal (Refereed)
    Abstract [en]

    Background: Cultivated crops have repeatedly faced new climatic conditions while spreading from their site oforigin. In Sweden, at the northernmost fringe of Europe, extreme conditions with temperature-limited growthseasons and long days require specific adaptation. Pea (Pisum sativum L.) has been cultivated in Sweden formillennia, allowing for adaptation to the local environmental conditions to develop. To study such adaptation, 15Swedish pea landraces were chosen alongside nine European landraces, seven cultivars and three wild accessions.Number of days to flowering (DTF) and other traits were measured and the diversity of the flowering time genesHIGH RESPONSE TO PHOTOPERIOD (HR), LATE FLOWERING (LF) and STERILE NODES (SN) was assessed. Furthermore, theexpression profiles of LF and SN were obtained.Results: DTF was positively correlated with the length of growing season at the site of origin (GSO) of the Swedishlandraces. Alleles at the HR locus were significantly associated with DTF with an average difference of 15.43 daysbetween the two detected haplotypes. LF expression was found to have a significant effect on DTF when analysedon its own, but not when HR haplotype was added to the model. HR haplotype and GSO together explained themost of the detected variation in DTF (49.6 %).Conclusions: We show local adaptation of DTF, primarily in the northernmost accessions, and links betweengenetic diversity and diversity in DTF. The links between GSO and genetic diversity of the genes are less clear-cutand flowering time adaptation seems to have a complex genetic background.

  • 1058.
    Vare, Daniel
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Groth, Petra
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Carlsson, Rickard
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Johansson, Fredrik
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Erixon, Klaus
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Jenssen, Dag
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    DNA interstrand crosslinks induce a potent replication block followed by formation and repair of double strand breaks in intact mammalian cells2012In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 11, no 12, p. 976-985Article in journal (Refereed)
    Abstract [en]

    DNA interstrand crosslinks (ICLs) are highly toxic lesions that covalently link both strands of DNA and distort the DNA helix. Crosslinking agents have been shown to stall DNA replication and failure to repair ICL lesions before encountered by replication forks may induce severe DNA damage. Most knowledge of the ICL repair process has been revealed from studies in bacteria and cell extracts. However, for mammalian cells the process of ICL repair is still unclear and conflicting data exist. In this study we have explored the fate of psoralen-induced ICLs during replication, by employing intact mammalian cells and novel techniques. By comparative studies distinguishing between effects by monoadducts versus ICLs, we have been able to link the block of replication to the ICLs induction. We found that the replication fork was equally blocked by ICLs in wild-type cells as in cells deficient in ERCC1/XPF and XRCC3. The formation of ICL induced double strand breaks (DSBs), detected by formation of 53PB1 foci, was equally induced in the three cell lines suggesting that these proteins are involved at a later step of the repair process. Furthermore, we found that forks blocked by ICLs were neither bypassed, restarted nor restored for several hours. We propose that this process is different from that taking place following monoadduct induction by UV-light treatment where replication bypass is taking place as an early step. Altogether our findings suggest that restoration of an ICL blocked replication fork, likely initiated by a DSB occurs relatively rapidly at a stalled fork, is followed by restoration, which seems to be a rather slow process in intact mammalian cells.

  • 1059.
    Varela, Inés
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Development of genetic tools for hydrogen production in cyanobacteria2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Today, due to the realization of problems such as climate change and limited resources, a lot of focus is being dedicated to find more sustainable and environmentally friendly ways of producing fuels. Cyanobacteria has the ability of meeting these challenges. However, production in cyanobacteria can still not compete with other fuels. Both due to the lack of genetic tools available and their inability of big scales production. During this thesis, we try to increase the amount of genetic tools available and increase hydrogen production in cyanobacteria by the expression of an exogenous gene. Heterocysts specific expression was studied and two promoter were created; one heterocyst specific and one specific for nitrogen deprived conditions. The two promoter can be use for further studies of heterocyst specific expression.

    The full text will be freely available from 2020-01-26 16:00
  • 1060.
    Vargas, Alexander O
    et al.
    Laboratorio de Ontogenia y Filogenia, Departamento de Biología, Facultad de Ciencias Universidad de Chile, Las Palermas, Ñuñoa, Santiago, Chile.
    Krabichler, Quirin
    TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
    Guerrero-Bosagna, Carlos
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    An Epigenetic Perspective on the Midwife Toad Experiments of Paul Kammerer (1880-1926)2017In: Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, ISSN 1552-5007, E-ISSN 1552-5015, Vol. 328, no 1-2, p. 179-192Article, review/survey (Refereed)
    Abstract [en]

    Paul Kammerer was the most outstanding neo-Lamarckian experimentalist of the early 20th century. He reported spectacular results in the midwife toad, including crosses of environmentally modified toads with normal toads, where acquired traits were inherited in Mendelian fashion. Accusations of fraud generated a great scandal, ending with Kammerer's suicide. Controversy reignited in the 1970s, when journalist Arthur Koestler argued against these accusations. Since then, others have argued that Kammerer's results, even if real, were not groundbreaking and could be explained by somatic plasticity, inadvertent selection, or conventional genetics. More recently, epigenetics has uncovered mechanisms by which inheritance can respond directly to environmental change, inviting a reanalysis of Kammerer's descriptions. Previous arguments for mere somatic plasticity have ignored the description of experiments showing heritable germ line modification. Alleged inadvertent selection associated with egg mortality can be discarded, since mortality decreased in a single generation, upon repeated exposures. The challenging implications did not escape the attention of Kammerer's noted contemporary, William Bateson, but he reacted with disbelief, thus encouraging fraud accusations. Nowadays, formerly puzzling phenomena can be explained by epigenetic mechanisms. Importantly, Kammerer described parent-of-origin effects, an effect of parental sex on dominance. Epigenetic mechanisms underlie these effects in genomic imprinting and experiments of transgenerational epigenetic inheritance. In the early 20th century, researchers had no reason to link them with the inheritance of acquired traits. Thus, the parent-of-origin effects in Kammerer's experiments specifically suggest authenticity. Ultimate proof should come from renewed experimentation. To encourage further research, we present a model of possible epigenetic mechanisms.

  • 1061.
    Ventham, N. T.
    et al.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Kennedy, N. A.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Adams, A. T.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Kalla, R.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Heath, S.
    CNAG-CRG, Centro Nacional de Ana´lisis Geno´mico, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
    O'Leary, K. R.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Drummond, H.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    IBD CHARACTER, consortium
    Wilson, D C
    Department of Child Life and Health, University of Edinburgh, Edinburgh, UK.
    Gut, I. G.
    CNAG-CRG, Centro Nacional de Ana´lisis Geno´mico, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
    Nimmo, E. R.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Satsangi, J.
    Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease2016In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, article id 13507Article in journal (Refereed)
    Abstract [en]

    Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8(+) T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression.

  • 1062.
    Vickovic, Sanja
    KTH, School of Biotechnology (BIO), Gene Technology.
    Three-dimensional whole transcriptome analysis of tissue for classification of breast cancer2017Manuscript (preprint) (Other academic)
  • 1063.
    Vickovic, Sanja
    KTH, School of Biotechnology (BIO), Gene Technology.
    Three-dimensional whole transcriptome analysis of tissue for classification of breast cancer. Submitted manuscript.2017Manuscript (preprint) (Other academic)
  • 1064.
    Vickovic, Sanja
    KTH, School of Biotechnology (BIO), Gene Technology.
    Transcriptome-wide analysis in cells and tissues2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    High-throughput sequencing has greatly influenced the amount of data produced and biological questions asked and answered. Sequencing approaches have also enabled rapid development of related technological fields such as single-cell and spatially resolved expression profiling. The introductory parts of this thesis give an overview of the basic molecular and technological apparatus needed to analyse the transcriptome in cells and tissues. This is succeeded by a summary of present investigations that report recent advancements in RNA profiling.

    RNA integrity needs to be preserved for accurate gene expression analysis. A method providing a low-cost alternative for RNA preservation was reported. Namely, a low concentration of buffered formaldehyde was used for fixation of human cell lines and peripheral blood cells (Paper I). The results from bulk RNA sequencing confirmed gene expression was not negatively impacted with the preservation procedure (r2>0.88) and that long-term storage of such samples was possible (r2=0.95). However, it is important to note that a small population of cells overexpressing a limited amount of genes can skew bulk gene expression analyses making them sufficient only in carefully designed studies. Therefore, gene expression should be investigated at the single cell resolution when possible. A method for high-throughput single cell expression profiling termed microarrayed single-cell sequencing was developed (Paper II). The method incorporated fluorescence-activated cell sorting, sample deposition and profiling of thousands of barcoded single cells in one reaction. After sample attachment to a barcoded array, a high-resolution image was taken which linked the position of each array barcode sequence to each individual deposited cell. The cDNA synthesis efficiency was estimated at 17.3% while detecting 27,427 transcripts per cell on average. Additionally, spatially resolved analysis is important in cell differentiation, organ development and pathological changes. Current methods are limited in terms of throughput, cost and time. For that reason, the spatial transcriptomics method was developed (Paper III). Here, the barcoded microarray was used to obtain spatially resolved expression profiles from tissue sections using the same imaging principle. The mouse olfactory bulb was profiled on a whole-transcriptome scale and the results showed that the expression correlated well (r2=0.94-0.97) as compared to bulk RNA sequencing. The method was 6.9% efficient, reported signal diffusion at ~2 μm and accurately deconvoluted layer-specific transcripts in an unbiased manner. Lastly, the spatial transcriptomics concept was applied to profile human breast tumours in three dimensions (Paper IV). Unbiased clustering revealed previously un-annotated regions and classified them as parts of the immune system, providing a detailed view into complex interactions and crosstalk in the whole tissue volume. Spatial tumour classification divulged that certain parts of the tumour clearly classified as other subtypes as compared to bulk analysis providing useful data for current practice diagnostics.

    The last part of the thesis discusses a look towards the future, how the presented methods could be used, improved upon or combined in translational research.

  • 1065.
    Videvall, Elin
    et al.
    Molecular Ecology and Evolution Lab, Department of Biology, Lund University, Lund, Sweden.
    Sletvold, Nina
    Plant Ecology and Evolution, Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Hagenblad, Jenny
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University.
    Ågren, Jon
    Plant Ecology and Evolution, Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Hansson, Bengt
    Molecular Ecology and Evolution Lab, Department of Biology, Lund University, Lund, Sweden.
    Strong Maternal Effects on Gene Expression inArabidopsis lyrata Hybrids2016In: Molecular Biology and Evolution, ISSN 0737-4038, Vol. 33, no 4, p. 984-994Article in journal (Refereed)
    Abstract [en]

    Hybridization between populations or species can have pronounced fitness consequences. Yet little is known about howhybridization affects gene regulation. Three main models have been put forward to explain gene expression patterns inhybrids: additive, dominance, or parental effects. Here, we use high throughput RNA-sequencing to examine the extent towhich hybrid gene expression follows predictions by each of the three models. We performed a reciprocal crossingexperiment between two differentiated populations of the perennial herb Arabidopsis lyrata and sequenced RNA inrosette leaves of 12-week-old plants grown in greenhouse conditions. The two parental populations had highly differentiatedgene expression patterns. In hybrids, a majority of genes showed intermediate expression relative to that of theirparental populations (i.e., additive effects), but expression was frequently more similar to the maternal than to theirpaternal population (i.e., maternal effects). Allele-specific expression analyses showed that in the vast majority of cases,genes with pronounced maternal effect expressed both the maternal and the paternal allele. Maternal effects on hybridgene expression have rarely been documented previously and our study suggests it could be more common thanpreviously assumed. Whether the maternal effect on gene expression persists to later life-stages, and whether thevariation in gene expression is manifested in other aspects of the phenotype, remain to be elucidated. Our findingsare relevant for understanding the consequences of outbreeding and hybridization and open up several questions forfuture studies.

  • 1066.
    Vijay, Nagarjun
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bossu, Christen M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stockholm Univ, Dept Zool Populat Genet, SE-10691 Stockholm, Sweden..
    Poelstra, Jelmer W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Weissensteiner, Matthias H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Suh, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kryukov, Alexey P.
    Russian Acad Sci, Inst Biol & Soil Sci, Far East Branch, Lab Evolutionary Zool & Genet, Vladivostok 690022, Russia..
    Wolf, Jochen B. W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Munich, Div Evolutionary Biol, Grosshaderner St 2, D-82152 Planegg Martinsried, Germany..
    Evolution of heterogeneous genome differentiation across multiple contact zones in a crow species complex2016In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, article id 13195Article in journal (Refereed)
    Abstract [en]

    Uncovering the genetic basis of species diversification is a central goal in evolutionary biology. Yet, the link between the accumulation of genomic changes during population divergence and the evolutionary forces promoting reproductive isolation is poorly understood. Here, we analysed 124 genomes of crow populations with various degrees of genome-wide differentiation, with parallelism of a sexually selected plumage phenotype, and ongoing hybridization. Overall, heterogeneity in genetic differentiation along the genome was best explained by linked selection exposed on a shared genome architecture. Superimposed on this common background, we identified genomic regions with signatures of selection specific to independent phenotypic contact zones. Candidate pigmentation genes with evidence for divergent selection were only partly shared, suggesting context-dependent selection on a multigenic trait architecture and parallelism by pathway rather than by repeated single-gene effects. This study provides insight into how various forms of selection shape genome-wide patterns of genomic differentiation as populations diverge.

  • 1067.
    Vila, C.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Leonard, J.A.
    Iriarte, A.
    O'Brien, S.J.
    Johnson, W.E.
    Wayne, R.K.
    Detecting the vanishing populations of the highly endangered Darwin's fox, Pseudalopex fulvipes.2004In: Animal Conservation, no 7, p. 147-153Article in journal (Refereed)
  • 1068.
    Vilà, C.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Leonard, J.A.
    Origen de los perros del Nuevo Mundo.2004In: Investigación y Ciencia., no 329, p. 33-34Article in journal (Other (popular scientific, debate etc.))
  • 1069.
    Vilà, C.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Seddon, J.
    Ellegren, H.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Genes of domestic mammals augmented by backcrossing with wild ancestors.2005In: Trends in Genetics, no 21, p. 214-218Article in journal (Refereed)
  • 1070.
    Voisin, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Biologie du Developpement et Reproduction, INRA, Jouy-en-Josas.
    Bioinformatic and Biostatistic Analysis of Epigenetic Data from Humans and Mice in the Context of Obesity and its Complications2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Worldwide obesity has more than doubled since 1980 and at least 2.8 million people die each year as a result of being overweight or obese. An elevated body weight is the result of the interplay between susceptibility gene variants and an obesogenic environment, and recent evidence shows that epigenetic processes are likely involved. The growing availability of high-throughput technologies has made it possible to assess quickly the entire epigenome of large samples at a relatively low cost. As a result, vast amounts of data have been generated and researchers are now confronted to both bioinformatic and biostatistic challenges to make sense of such data in the context of obesity and its complications. In this doctoral thesis, we explored associations between the human blood methylome and obesity-associated gene variants as well as dietary fat quality and quantity. We used well described preprocessing techniques and statistical methods, along with publicly available data from consortiums and other research groups, as well as tools for pathway enrichment and chromatin state inference. We found associations between obesityassociated SNPs and methylation levels at proximal promoters and enhancers, and some of these associations were replicated in multiple tissues. We also found that contrary to dietary fat quantity, dietary fat quality associates with methylation levels in the promoter of genes involved in metabolic pathways. Then, using a gene-targeted approach, we looked at the impact of an acute environmental stress (sleep loss) on the methylation and transcription levels of circadian clock genes in skeletal muscle and adipose tissue of healthy men. We found that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in a tissue-specific manner. Finally, we looked at the effects of chronic maternal obesity and subsequent weight loss on the transcription of epigenetic machinery genes in the fetus and placenta of mice. We found that the transcription of epigenetic machinery genes is highly sensitive to maternal weight trajectories, and particularly those of the histone acetylation pathway. Overall, this thesis demonstrated that genetics, obesogenic environment stimuli and maternal programming impact epigenetic marks at genomic locations relevant in the pathogenesis of obesity.

  • 1071.
    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.

  • 1072.
    Waak, Elisabet
    et al.
    Arla FoU, Stockholm, Sweden.
    Tham, Wilhelm
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Fingerprinting of Listeria monocytogenes isolated in silos for raw whole milk of a dairy plant2000In: Nordic PFGE meeting. January 27–28, 2000. Collection of Abstracts, Department of Food Hygiene, Faculty of Veterinary Medicine, SLU, Uppsala / [ed] Marie-Louise Danielsson-Tham och Wilhelm Tham, Uppsala: Dep of Food Hygiene, Faculty of Veterinary Medicine, SLU , 2000, p. 28-28Conference paper (Refereed)
  • 1073.
    Wagner, Gerhart
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Romby, Pascale
    Univ Strasbourg, CNRS, IBMC, Architecture & Reactivite ARN, Strasbourg, France..
    Small RNAs in Bacteria and Archaea: Who They Are, What They Do, and How They Do It2015In: Advances in Genetics, Vol 90, Elsevier, 2015, p. 133-208Chapter in book (Refereed)
    Abstract [en]

    Small RNAs are ubiquitously present regulators in all kingdoms of life. Most bacterial and archaeal small RNAs (sRNAs) act by antisense mechanisms on multiple target mRNAs, thereby globally affecting essentially any conceivable traitestress responses, adaptive metabolic changes, virulence etc. The sRNAs display many distinct mechanisms of action, most of them through effects on target mRNA translation and/or stability, and helper proteins like Hfq often play key roles. Recent data highlight the interplay between posttranscriptional control by sRNAs and transcription factor-mediated transcriptional control, and cross talk through mutual regulation of regulators. Based on the properties that distinguish sRNA-type from transcription factors-type control, we begin to glimpse why sRNAs have evolved as a second, essential layer of gene regulation. This review will discuss the prevalence of sRNAs, who they are, what biological roles they play, and how they carry out their functions.

  • 1074.
    Wahlberg, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Chicken Genomics - Linkage and QTL mapping2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis presents results from genetic studies conducted in the chicken (Gallus gallus). The domestication of chicken is believed to have been initiated approximately 7,000 – 9,000 years ago in Southeast Asia. Since that time, selective breeding has altered the appearance of the wild ancestor, creating highly specialized chicken lines developed for egg and meat production.

    The first part of this thesis describes a detailed genetic analysis conducted on an F2 intercross between two phenotypically diverse chicken lines. The two parental lines used in this experiment originated from the same base population and have been developed by divergent selection for juvenile body-weight. Selection during forty generations has resulted in an eight-fold difference in body-weight between the High-Weight Selected (HWS) and Low-Weight Selected (LWS) line. In an attempt to identify the genetic factors differentiating the two lines, a large intercross population was bred to map Quantitative Trait Loci (QTL) affecting body-weight traits. A linkage map was constructed which included 434 genetic markers covering 31 of the 38 chicken autosomes. Although there is a dramatic phenotypic difference between the two founder lines, the QTL analysis for marginal effect could only identify seven QTL, each with small additive effects, influencing body-weight. We extended the genetic analysis to also include a model testing for pair-wise interactions between loci (epistasis). The analysis revealed 15 QTL pairs that affect body-weight and several of those formed a network of interacting loci. These results suggest that the genetic basis for the large difference in body-weight is most likely a result of a combined effect of multiple genetic factors, including QTL with small additive effects in combination with pair-wise interactions between QTL.

    The second part of this thesis presents two linkage maps. The first map constructed was of the chicken Z chromosome, the second used a genome-wide marker set, including 12,945 SNP markers, to build an updated consensus map of the chicken genome. The resulting consensus map includes 9,268 genetic markers and covers 33 chromosomes, still leaving five microchromosomes without marker coverage. The genome average rate of recombination was estimated to 3.1 cM/Mb, but varied considerably between and within chromosomes. A general trend of elevated recombination rates towards telomeric ends and lower rates near centromeres was observed. This was in concordance to previous reports from mammalian species. Recombination rates in chicken were also found to be highly positively correlated with GC-rich sequences.

  • 1075.
    Waldmann, Patrik
    et al.
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, The Institute of Technology. University of Natural Resources and Life Sciences, Vienna, Austria .
    Mészáros, Gábor
    University of Natural Resources and Life Sciences, Vienna, Austria.
    Gredler, Birgit
    Qualitas AG, Zug, Switzerland.
    Fuerst, Christian
    ZuchtData EDV-Dienstleistungen GmbH, Vienna, Austria .
    Sölkner, Johann
    University of Natural Resources and Life Sciences, Vienna, Austria .
    Evaluation of the lasso and the elastic net in genome-wide association studies2013In: Frontiers in Genetics, ISSN 1664-8021, E-ISSN 1664-8021, Vol. 4, no 270Article in journal (Refereed)
    Abstract [en]

    The number of publications performing genome-wide association studies (GWAS) has increased dramatically. Penalized regression approaches have been developed to overcome the challenges caused by the high dimensional data, but these methods are relatively new in the GWAS field. In this study we have compared the statistical performance of two methods (the least absolute shrinkage and selection operator—lasso and the elastic net) on two simulated data sets and one real data set from a 50 K genome-wide single nucleotide polymorphism (SNP) panel of 5570 Fleckvieh bulls. The first simulated data set displays moderate to high linkage disequilibrium between SNPs, whereas the second simulated data set from the QTLMAS 2010 workshop is biologically more complex. We used cross-validation to find the optimal value of regularization parameter λ with both minimum MSE and minimum MSE + 1SE of minimum MSE. The optimal λ values were used for variable selection. Based on the first simulated data, we found that the minMSE in general picked up too many SNPs. At minMSE + 1SE, the lasso didn't acquire any false positives, but selected too few correct SNPs. The elastic net provided the best compromise between few false positives and many correct selections when the penalty weight α was around 0.1. However, in our simulation setting, this α value didn't result in the lowest minMSE + 1SE. The number of selected SNPs from the QTLMAS 2010 data was after correction for population structure 82 and 161 for the lasso and the elastic net, respectively. In the Fleckvieh data set after population structure correction lasso and the elastic net identified from 1291 to 1966 important SNPs for milk fat content, with major peaks on chromosomes 5, 14, 15, and 20. Hence, we can conclude that it is important to analyze GWAS data with both the lasso and the elastic net and an alternative tuning criterion to minimum MSE is needed for variable selection.

  • 1076.
    Waldén, Tomas
    et al.
    The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden.
    Hansen, Ida R.
    Timmons, James A.
    Cannon, Barbara
    Nedergaard, Jan
    Recruited vs. nonrecruited molecular signatures of brown, "brite" and white adipose tissues2012In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 302, no 1, p. E19-E31Article in journal (Refereed)
    Abstract [en]

    Mainly from cell culture studies, a series of genes that have been suggested to be characteristic of different types of adipocytes have been identified. Here we have examined gene expression patterns in nine defined adipose depots: interscapular BAT, cervical BAT, axillary BAT, mediastinic BAT, cardiac WAT, inguinal WAT, retroperitoneal WAT, mesenteric WAT, and epididymal WAT. We found that each depot displayed a distinct gene expression fingerprint but that three major types of depots were identifiable: the brown, the brite, and the white. Although differences in gene expression pattern were generally quantitative, some gene markers showed, even in vivo, remarkable depot specificities: Zic1 for the classical BAT depots, Hoxc9 for the brite depots, Hoxc8 for the brite and white in contrast to the brown, and Tcf21 for the white depots. The effect of physiologically induced recruitment of thermogenic function (cold acclimation) on the expression pattern of the genes was quantified; in general, the depot pattern dominated over the recruitment effects. The significance of the gene expression patterns for classifying the depots and for understanding the developmental background of the depots is discussed, as are the possible regulatory functions of the genes.                   

  • 1077.
    Wallberg, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Glemin, Sylvain
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Webster, Matthew T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Extreme Recombination Frequencies Shape Genome Variation and Evolution in the Honeybee, Apis mellifera2015In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 4, article id e1005189Article in journal (Refereed)
    Abstract [en]

    Meiotic recombination is a fundamental cellular process, with important consequences for evolution and genome integrity. However, we know little about how recombination rates vary across the genomes of most species and the molecular and evolutionary determinants of this variation. The honeybee, Apis mellifera, has extremely high rates of meiotic recombination, although the evolutionary causes and consequences of this are unclear. Here we use patterns of linkage disequilibrium in whole genome resequencing data from 30 diploid honeybees to construct a fine-scale map of rates of crossing over in the genome. We find that, in contrast to vertebrate genomes, the recombination landscape is not strongly punctate. Crossover rates strongly correlate with levels of genetic variation, but not divergence, which indicates a pervasive impact of selection on the genome. Germ-line methylated genes have reduced crossover rate, which could indicate a role of methylation in suppressing recombination. Controlling for the effects of methylation, we do not infer a strong association between gene expression patterns and recombination. The site frequency spectrum is strongly skewed from neutral expectations in honeybees: rare variants are dominated by AT-biased mutations, whereas GC-biased mutations are found at higher frequencies, indicative of a major influence of GC-biased gene conversion (gBGC), which we infer to generate an allele fixation bias 5 - 50 times the genomic average estimated in humans. We uncover further evidence that this repair bias specifically affects transitions and favours fixation of CpG sites. Recombination, via gBGC, therefore appears to have profound consequences on genome evolution in honeybees and interferes with the process of natural selection. These findings have important implications for our understanding of the forces driving molecular evolution.

  • 1078.
    Wallberg, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Han, Fan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wellhagen, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dahle, Bjørn
    Kawata, Masakado
    Haddad, Nizar
    Simões, Zilá Luz Paulino
    Allsopp, Mike H
    Kandemir, Irfan
    De la Rúa, Pilar
    Pirk, Christian W
    Webster, Matthew T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A worldwide survey of genome sequence variation provides insight into the evolutionary history of the honeybee Apis mellifera2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 10, p. 1081-1088Article in journal (Refereed)
    Abstract [en]

    The honeybee Apis mellifera has major ecological and economic importance. We analyze patterns of genetic variation at 8.3 million SNPs, identified by sequencing 140 honeybee genomes from a worldwide sample of 14 populations at a combined total depth of 634×. These data provide insight into the evolutionary history and genetic basis of local adaptation in this species. We find evidence that population sizes have fluctuated greatly, mirroring historical fluctuations in climate, although contemporary populations have high genetic diversity, indicating the absence of domestication bottlenecks. Levels of genetic variation are strongly shaped by natural selection and are highly correlated with patterns of gene expression and DNA methylation. We identify genomic signatures of local adaptation, which are enriched in genes expressed in workers and in immune system- and sperm motility-related genes that might underlie geographic variation in reproduction, dispersal and disease resistance. This study provides a framework for future investigations into responses to pathogens and climate change in honeybees.

  • 1079.
    Wallberg, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Schoening, Caspar
    Inst Bee Res, Hohen Neuendorf, Germany..
    Webster, Matthew Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hasselmann, Martin
    Univ Hohenheim, Stuttgart, Germany..
    Two extended haplotype blocks are associated with adaptation to high altitude habitats in East African honey bees2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 5, article id e1006792Article in journal (Refereed)
    Abstract [en]

    Understanding the genetic basis of adaption is a central task in biology. Populations of the honey bee Apis mellifera that inhabit the mountain forests of East Africa differ in behavior and morphology from those inhabiting the surrounding lowland savannahs, which likely reflects adaptation to these habitats. We performed whole genome sequencing on 39 samples of highland and lowland bees from two pairs of populations to determine their evolutionary affinities and identify the genetic basis of these putative adaptations. We find that in general, levels of genetic differentiation between highland and lowland populations are very low, consistent with them being a single panmictic population. However, we identify two loci on chromosomes 7 and 9, each several hundred kilobases in length, which exhibit near fixation for different haplotypes between highland and lowland populations. The highland haplotypes at these loci are extremely rare in samples from the rest of the world. Patterns of segregation of genetic variants suggest that recombination between haplotypes at each locus is suppressed, indicating that they comprise independent structural variants. The haplotype on chromosome 7 harbors nearly all octopamine receptor genes in the honey bee genome. These have a role in learning and foraging behavior in honey bees and are strong candidates for adaptation to highland habitats. Molecular analysis of a putative breakpoint indicates that it may disrupt the coding sequence of one of these genes. Divergence between the highland and lowland haplotypes at both loci is extremely high suggesting that they are ancient balanced polymorphisms that greatly predate divergence between the extant honey bee subspecies.

  • 1080.
    Wallin, Anita
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Fysiologisk botanik.
    Iwarsson, Mattias
    Botanical Garden.
    Artonårig provodling av mikroförökad masurbjörk2004In: Lustgården, Vol. 84, p. 35-40Article in journal (Other scientific)
    Abstract [en]

    Propagation and cultivation of masur figure birch. Figure wood has fascinated foresters and craftsmen for centuries. The curly birch, Betula pendula var. carelica, is the most common curly-grained wood, displaying a characteristic pattern of curly fibers. Three different types of curly birch, one with protuberances, one with neck masur and one slow-growing clone, were selected and micropropagated 1985 and planted at Pustnäs at Fyrisån, Uppsala, 1987. Micropropagated individuals of the same clone are very similar in tree morphology, growth and masur characteristics.

    Furthermore a birch from Valls Hage, featuring extreme tumours were micropropageted and plants were replanted in the arboretum.

  • 1081.
    Wallin, Anita
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. fysiologisk botanik.
    Iwarsson, Mattias
    Botanical Garden.
    Mikroförökning av björkar2004In: Lustgården, ISSN 0349-0033, Vol. 84, p. 41-54Article in journal (Other (popular scientific, debate etc.))
    Abstract [en]

    To preserv biodiversity, individual birches of special interest have been propagated in-vitro. All selected clones have characteristics that should have been lost if sexually propagated. Many of the propagated birches were selected and cultivated in Botanical gardens 50 years ago and must be renewed if they shall be saved for future.

    A technical description of the micropropagation process is given, and the development of in-vitro shoots is visually documented

    The history and taxonomy of birches from the time of Carl Linnaeus to present day are reviewed.

  • 1082.
    Waluk, Dominik Paweł
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Biosynthesis and physiological functions of N-acyl amino acids2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    N-acyl amino acids are lipid signalling molecules that have recently been identified in biological systems. These lipids are structurally related to the endocannabinoids, although they do not activate cannabinoid receptors. In 2001, N-arachidonoyl glycine was the first signalling lipid in this group to be identified in bovine and rat brain and since then, about 50 novel N-acyl amino acids have been identified in mammalian systems. These N-acyl amino acids are involved in regulating pain processes, are anti-inflammatory and regulate body temperature, but the metabolic pathways for production and metabolism remain poorly understood.

    This thesis focussed on the identification of pathways for production and regulation of N-acyl amino acids, in particular N-acyl glycines, and in identifying physiological functions for N-acyl amino acids (particularly N-acyl taurines). Our results identified an enzymatic pathway for production of N-acyl glycines in human and we identified that the human glycine N-acyltransferase-like 2 (hGLYATL2) conjugates (amidates) medium- and long-chain, saturated and unsaturated acyl-CoAs with glycine, to produce N-acyl glycines, with the preferential production of N-oleoyl glycine. Furthermore, we have characterized two other members of the gene family of glycine N-acyltransferases (GLYATs) in human, the hGLYATL1 and hGLYATL3 that may be involved in the production of N-acyl amino acids.

    As N-acyl glycines are bioactive signalling molecules, it is likely their production requires a rapid on/off switch. The post-translational modification of proteins can result in enzyme regulation, without the need for transcriptional regulation. We have identified that hGLYATL2 is regulated by acetylation/deacetylation on lysine 19, and using mutation analysis, we show that deacetylation of lysine 19 is important for full enzyme activity.

    The physiological functions of N-acyl amino acids are not well studied to date. In this thesis, we have identified that N-arachidonoyl taurine and N-oleoyl taurine trigger insulin secretion by increasing the calcium flux in pancreatic b-cells via the activation of transient receptor potential vanilloid subfamily 1 (TRPV1).

    This work on N-acyl amino acids has led us to identify new pathways and physiological functions for these lipid signalling molecules, which advances our knowledge of the importance of these lipids in mammalian systems.

  • 1083.
    Walum, Hasse
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Westberg, Lars
    Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Magnusson, Patrik K. E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sex differences in jealousy: a population-based twin study in Sweden2013In: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 16, no 5, p. 941-946Article in journal (Refereed)
    Abstract [en]

    According to the theory of evolved sex differences in jealousy, the challenge for women to ensure paternal investment increased their jealousy response to emotional infidelity, whereas paternal uncertainty exerted selective pressures that shaped men to become more distressed by sexual infidelity. Several studies have investigated whether the effect of these sexually dimorphic selection pressures can be detected in contemporary human populations, with conflicting results. To date, no genetically informed studies of sex differences in jealousy have been conducted. We used data from the Screening Across the Lifespan of Twins Younger (SALTY) sample, containing information concerning self-rated jealousy from 3,197 complete twin pairs collected by the Swedish Twin Registry. Intra-class correlations and structural equation models were used to assess the genetic influence on jealousy and to investigate sex differences at genetic level. We saw a highly significant sex effect on the relationship between infidelity types, indicating that men, relative to women, reported greater jealousy in response to sexual infidelity than in response to emotional infidelity. The twin models revealed significant heritabilities for both sexual (32%) and emotional (26%) jealousy. The heritabilities were of a similar magnitude in both sexes, and no qualitative sex differences could be detected. We show for the first time that variance in jealousy is to some extent explained by genetic factors. Even though our results from the mean value analyses are in line with the theory of evolved sex differences in jealousy, we could not identify any sex differences on a genetic level.

  • 1084.
    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.

  • 1085.
    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.

  • 1086.
    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.

  • 1087.
    Wang, Biao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Ekblom, Robert
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Bunikis, Ignas
    Siitari, Heli
    Höglund, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Whole genome sequencing of the black grouse (Tetrao tetrix): reference guided assembly suggests faster-Z and MHC evolution2014In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, no 180, p. 1-13Article in journal (Refereed)
  • 1088.
    Wang, Biao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Ekblom, Robert
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Strand, Tanja
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Portela-Bens, Silvia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Höglund, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Sequencing of the core MHC region of black grouse (Tetrao tetrix) and comparative genomics of the galliform MHC2012In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, p. 553-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:The MHC, which is regarded as the most polymorphic region in the genomes of jawed vertebrates, plays a central role in the immune system by encoding various proteins involved in the immune response. The chicken MHC-B genomic region has a highly streamlined gene content compared to mammalian MHCs. Its core region includes genes encoding Class I and Class IIB molecules but is only ~92Kb in length. Sequences of other galliform MHCs show varying degrees of similarity as that of chicken. The black grouse (Tetrao tetrix) is a wild galliform bird species which is an important model in conservation genetics and ecology. We sequenced the black grouse core MHC-B region and combined this with available data from related species (chicken, turkey, gold pheasant and quail) to perform a comparative genomics study of the galliform MHC. This kind of analysis has previously been severely hampered by the lack of genomic information on avian MHC regions, and the galliformes is still the only bird lineage where such a comparison is possible.RESULTS:In this study, we present the complete genomic sequence of the MHC-B locus of black grouse, which is 88,390 bp long and contains 19 genes. It shows the same simplicity as, and almost perfect synteny with, the corresponding genomic region of chicken. We also use 454-transcriptome sequencing to verify expression in 17 of the black grouse MHC-B genes. Multiple sequence inversions of the TAPBP gene and TAP1-TAP2 gene block identify the recombination breakpoints near the BF and BLB genes. Some of the genes in the galliform MHC-B region also seem to have been affected by selective forces, as inferred from deviating phylogenetic signals and elevated rates of non-synonymous nucleotide substitutions.CONCLUSIONS:We conclude that there is large synteny between the MHC-B region of the black grouse and that of other galliform birds, but that some duplications and rearrangements have occurred within this lineage. The MHC-B sequence reported here will provide a valuable resource for future studies on the evolution of the avian MHC genes and on links between immunogenetics and ecology of black grouse.

  • 1089. Wang, Chunlin
    et al.
    Sanders, Catherine M.
    Yang, Qunying
    Schroeder, Harry W., Jr.
    Wang, Elijah
    Babrzadeh, Farbod
    Stanford Genome Technology Center, United States .
    Gharizadeh, Baback
    Myers, Richard M.
    Hudson, James R., Jr.
    Davis, Ronald W.
    Han, Jian
    High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 4, p. 1518-1523Article in journal (Refereed)
    Abstract [en]

    Developing T cells face a series of cell fate choices in the thymus and in the periphery. The role of the individual T cell receptor (TCR) in determining decisions of cell fate remains unresolved. The stochastic/selection model postulates that the initial fate of the cell is independent of TCR specificity, with survival dependent on additional TCR/coreceptor "rescue" signals. The "instructive" model holds that cell fate is initiated by the interaction of the TCR with a cognate peptide-MHC complex. T cells are then segregated on the basis of TCR specificity with the aid of critical coreceptors and signal modulators [Chan S, Correia-Neves M, Benoist C, Mathis (1998) Immunol Rev 165: 195-207]. The former would predict a random representation of individual TCR across divergent T cell lineages whereas the latter would predict minimal overlap between divergent T cell subsets. To address this issue, we have used high-throughput sequencing to evaluate the TCR distribution among key T cell developmental and effector subsets from a single donor. We found numerous examples of individual subsets sharing identical TCR sequence, supporting a model of a stochastic process of cell fate determination coupled with dynamic patterns of clonal expansion of T cells bearing the same TCR sequence among both CD4(+) and CD8+ populations.

  • 1090.
    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 Science.
    Ding, Jihua
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences.
    Tan, Biyue
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Stora Enso AB.
    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
    Wallenberg Advanced Bioinformatics Infrastructure, Science for Life Laboratory, Uppsala University.
    Nystedt, Björn
    Wallenberg Advanced Bioinformatics Infrastructure, Science for Life Laboratory, Uppsala University.
    Scofield, Douglas G.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Ecology and Genetics, Evolutionary Biology, Uppsala University.
    Nilsson, Ove
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences.
    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. Department of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences.
    A major locus controls local adaptation and adaptive life history variation in a perennial plantManuscript (preprint) (Other academic)
    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 their 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). We discover a single genomic region containing the PtFT2 gene that mediates local adaptation in the timing of bud set and that 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 affect the phenotypic variation in bud set that we observe in wild natural populations.

    Conclusions: Our results reveal a major effect locus that determine the timing of bud set and that have 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.

  • 1091.
    Wang, Jing
    et al.
    Umea Univ, Dept Ecol & Environm Sci, Umea, SE, Sweden..
    Street, Nathaniel R.
    Umea Univ, Dept Plant Physiol, Umea Plant Sci Ctr, S-90187 Umea, SE, Sweden..
    Scofield, Douglas G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Umea Univ, Dept Ecol & Environm Sci, Umea, SE, Sweden..
    Ingvarsson, Par K.
    Umea Univ, Dept Ecol & Environm Sci, Umea, SE, Sweden..
    Variation in Linked Selection and Recombination Drive Genomic Divergence during Allopatric Speciation of European and American Aspens2016In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 33, no 7, p. 1754-1767Article in journal (Refereed)
    Abstract [en]

    Despite the global economic and ecological importance of forest trees, the genomic basis of differential adaptation and speciation in tree species is still poorly understood. Populus tremula and Populus tremuloides are two of the most widespread tree species in the Northern Hemisphere. Using whole-genome re-sequencing data of 24 P. tremula and 22 P. tremuloides individuals, we find that the two species diverged similar to 2.2-3.1 million years ago, coinciding with the severing of the Bering land bridge and the onset of dramatic climatic oscillations during the Pleistocene. Both species have experienced substantial population expansions following long-term declines after species divergence. We detect widespread and heterogeneous genomic differentiation between species, and in accordance with the expectation of allopatric speciation, coalescent simulations suggest that neutral evolutionary processes can account for most of the observed patterns of genetic differentiation. However, there is an excess of regions exhibiting extreme differentiation relative to those expected under demographic simulations, which is indicative of the action of natural selection. Overall genetic differentiation is negatively associated with recombination rate in both species, providing strong support for a role of linked selection in generating the heterogeneous genomic landscape of differentiation between species. Finally, we identify a number of candidate regions and genes that may have been subject to positive and/or balancing selection during the speciation process.

  • 1092.
    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.

  • 1093.
    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.

  • 1094.
    Wang, Mi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Uebbing, Severin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Allele-specific gene expression inferred by a Bayesian negative binomial approach indicates abundant cis-regulatory variation in natural flycatcher populationsManuscript (preprint) (Other academic)
    Abstract [en]

    Polymorphisms in cis-regulatory sequences can make the two alleles of a gene be expressed at different levels, providing a starting point for the evolution of divergence in gene expression. However, little is known about the genome-wide abundance of regulatory variation in natural populations. We performed RNA-seq of multiple tissues from population samples of two closely related flycatcher species and developed a Bayesian algorithm that maximises data usage by borrowing overdispersion estimates over the whole dataset and combines several SNPs per transcript to detect allele-specific expression (ASE). Of 2,576 transcripts analysed in collared flycatcher, ASE was detected in 185 (7.2%). A similar frequency was seen in the pied flycatcher but these frequencies are likely to be underestimates for several reasons. The proportion of ASE transcripts varied among tissues, being lowest in testis and highest in muscle. Often, ASE was seen in several tissues for particular gene-individual combinations. This is one of only very few large-scale studies investigating the incidence of ASE in the wild. The results suggest that genetic variation in regulatory sequences commonly affect gene expression in natural populations and that it provides a seedbed for phenotypic evolution via divergence in gene expression.

  • 1095.
    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.

  • 1096.
    Wang, Z. Q.
    et al.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria; nternational Agency for Research on Cancer (IARC), F-69008 Lyon, France.
    Stingl, L.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
    Morrison, C.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
    Jantsch, M.
    Department of Cytology and Genetics, University of Vienna, A-1030 Vienna, Austria.
    Los, Marek Jan
    Department of Molecular Oncology/ Pediatry, German Cancer Research Center, D-69120 Heidelberg, Germany.
    Schulze-Osthoff, Klaus
    Medical Clinics, University of Tübingen, D-72076 Tübingen, Germany.
    Wagner, E. F.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
    PARP is important for genomic stability but dispensable in apoptosis1997In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 11, no 18, p. 2347-2358Article in journal (Refereed)
    Abstract [en]

    Mice lacking the gene encoding poly(ADP-ribosyl) transferase (PARP or ADPRT) display no phenotypic abnormalities, although aged mice are susceptible to epidermal hyperplasia and obesity in a mixed genetic background. Whereas embryonic fibroblasts lacking PARP exhibit normal DNA excision repair, they grow more slowly in vitro. Here we investigated the putative roles of PARP in cell proliferation, cell death, radiosensitivity, and DNA recombination, as well as chromosomal stability. We show that the proliferation deficiency in vitro and in vive is most likely caused by a hypersensitive response to environmental stress. Although PARP is specifically cleaved during apoptosis, cells Backing this molecule apoptosed normally in response to treatment with anti-Fas, tumor neurosis factor alpha, gamma-irradiation, and dexamethasone, indicating that PARP is dispensable in apoptosis and that PARP-/-thymocytes are not hypersensitive to ionizing radiation. Furthermore, the capacity of mutant cells to carry out immunoglobulin class switching and V(D)J recombination is normal. Finally, primary PARP mutant fibroblasts and splenocytes exhibited an elevated frequency of spontaneous sister chromatid exchanges and elevated micronuclei formation after treatment with genotoxic agents, establishing an important role for PARP in the maintenance of genomic integrity.

  • 1097. Wanschers, Bas F. J.
    et al.
    Szklarczyk, Radek
    van den Brand, Mariel A. M.
    Jonckheere, An
    Suijskens, Janneke
    Smeets, Roel
    Rodenburg, Richard J.
    Stephan, Katharina
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Helland, Ingrid B.
    Elkamil, Areej
    Rootwelt, Terje
    Ott, Martin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    van den Heuvel, Lambert
    Nijtmans, Leo G.
    Huynen, Martijn A.
    A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability2014In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 23, p. 6356-6365Article in journal (Refereed)
    Abstract [en]

    Complex III (cytochrome bc(1)) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c. Its assembly requires the coordinated expression of mitochondrial-encoded cytochrome b and nuclear-encoded subunits and assembly factors. Complex III deficiency is a severe multisystem disorder caused by mutations in subunit genes or assembly factors. Sequence-profile-based orthology predicts C11orf83, hereafter named UQCC3, to be the ortholog of the fungal complex III assembly factor CBP4. We describe a homozygous c.59T > A missense mutation in UQCC3 from a consanguineous patient diagnosed with isolated complex III deficiency, displaying lactic acidosis, hypoglycemia, hypotonia and delayed development without dysmorphic features. Patient fibroblasts have reduced complex III activity and lower levels of the holocomplex and its subunits than controls. They have no detectable UQCC3 protein and have lower levels of cytochrome b protein. Furthermore, in patient cells, cytochrome b is absent from a high-molecular-weight complex III. UQCC3 is reduced in cells depleted for the complex III assembly factors UQCC1 and UQCC2. Conversely, absence of UQCC3 in patient cells does not affect UQCC1 and UQCC2. This suggests that UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 and is consistent with what is known about the function of Cbp4 and of the fungal orthologs of UQCC1 and UQCC2, Cbp3 and Cbp6. We conclude that UQCC3 functions in complex III assembly and that the c.59T > A mutation has a causal role in complex III deficiency.

  • 1098.
    Warnefors, Maria
    et al.
    Heidelberg University of ZMBH, Germany.
    Mossinger, Katharina
    Heidelberg University of ZMBH, Germany.
    Halbert, Jean
    University of Lausanne, Switzerland.
    Studer, Tania
    Heidelberg University of ZMBH, Germany.
    VandeBerg, John L.
    University of Texas Rio Grande Valley, TX 78520 USA.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Fallahshahroudi, Amir
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Kaessmann, Henrik
    Heidelberg University of ZMBH, Germany.
    Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation2017In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 27, no 12, p. 1961-1973Article in journal (Refereed)
    Abstract [en]

    Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that autosomal testis-biased miRNAs tend to be somatically male-biased, whereas autosomal ovary-biased miRNAs are female-biased, possibly due to broad hormonal control. In chicken, which has a Z/W sex chromosome system, expression output of genes on the Z Chromosome is expected to be male-biased, since there is no global dosage compensation mechanism that restores expression in ZW females after almost all genes on the W Chromosome decayed. Nevertheless, we found that the dominant liver miRNA, miR-122-5p, is Z-linked but expressed in an unbiased manner, due to the unusual retention of a W-linked copy. Another Z-linked miRNA, the male-biased miR-2954-3p, shows conserved preference for dosage-sensitive genes on the Z Chromosome, based on computational and experimental data from chicken and zebra finch, and acts to equalize male-to-female expression ratios of its targets. Unexpectedly, our findings thus establish miRNA regulation as a novel gene-specific dosage compensation mechanism.

  • 1099. Wayne, R.K
    et al.
    Geffen, E.
    Vilà, C.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Conservation Genetics of Canids2004In: Canids: Foxes, Wolves, Jackals and Dogs.: Status Survey and Conservation Aciton Plan, IUCN/SSC Canid Specialist Group, Gland, Switzerland. Cambridge, UK. , 2004Chapter in book (Other scientific)
  • 1100. Wayne, R.K.
    et al.
    Geffen, E.
    Vilà, C.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Population and conservation genetics of canids.2004In: Biology and Conservation of Wild Canids., Oxford University Press , 2004Chapter in book (Other scientific)
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