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  • 101.
    Libby, Eric
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Modularity of the life cycle2019In: Nature Ecology & Evolution, E-ISSN 2397-334X, Vol. 3, no 8, p. 1142-1143Article in journal (Other academic)
    Abstract [en]

    Life stages in Bacillus subtilis are controlled by regulatory blocks that can be kept or lost across species in response to selection in different environments.

  • 102. Lin, Yao-Cheng
    et al.
    Wang, Jing
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Norway.
    Delhomme, Nicolas
    Schiffthaler, Bastian
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Sundström, Görel
    Zuccolo, Andrea
    Nystedt, Björn
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    de la Torre, Amanda
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). School of Forestry, Northern Arizona University, Flagstaff, AZ.
    Cossu, Rosa M.
    Hoeppner, Marc P.
    Lantz, Henrik
    Scofield, Douglas G.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Ecology and Genetics: Evolutionary Biology, Uppsala University, Sweden; Uppsala Multidisciplinary Center for Advanced Computational Science, Uppsala University, Sweden.
    Zamani, Neda
    Johansson, Anna
    Mannapperuma, Chanaka
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Robinson, Kathryn M.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Mähler, Niklas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Leitch, Ilia J.
    Pellicer, Jaume
    Park, Eung-Jun
    Van Montagu, Marc
    Van de Peer, Yves
    Grabherr, Manfred
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Plant Biology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 46, p. E10970-E10978Article in journal (Refereed)
    Abstract [en]

    The Populus genus is one of the major plant model systems, but genomic resources have thus far primarily been available for poplar species, and primarily Populus trichocarpa (Torr. & Gray), which was the first tree with a whole-genome assembly. To further advance evolutionary and functional genomic analyses in Populus, we produced genome assemblies and population genetics resources of two aspen species, Populus tremula L. and Populus tremuloides Michx. The two aspen species have distributions spanning the Northern Hemisphere, where they are keystone species supporting a wide variety of dependent communities and produce a diverse array of secondary metabolites. Our analyses show that the two aspens share a similar genome structure and a highly conserved gene content with P. trichocarpa but display substantially higher levels of heterozygosity. Based on population resequencing data, we observed widespread positive and negative selection acting on both coding and noncoding regions. Furthermore, patterns of genetic diversity and molecular evolution in aspen are influenced by a number of features, such as expression level, coexpression network connectivity, and regulatory variation. To maximize the community utility of these resources, we have integrated all presented data within the PopGenIE web resource (PopGenIE.org).

  • 103.
    Lind, Peter A.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
    Arvidsson, Lars
    Berg, Otto G
    Andersson, Dan I
    Variation in mutational robustness between different proteins and the predictability of fitness effects2017In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 2, p. 408-418Article in journal (Refereed)
    Abstract [en]

    Random mutations in genes from disparate protein classes may have different distributions of fitness effects (DFEs) depending on different structural, functional and evolutionary constraints. We measured the fitness effects of 156 single mutations in the genes encoding AraC (transcription factor), AraD (enzyme), and AraE (transporter) used for bacterial growth on L- arabinose. Despite their different molecular functions these genes all had bimodal DFEs with most mutations either being neutral or strongly deleterious, providing a general expectation for the DFE. This contrasts with the unimodal DFEs previously obtained for ribosomal protein genes where most mutations were slightly deleterious. Based on theoretical considerations, we suggest that the 33-fold higher average mutational robustness of ribosomal proteins is due to stronger selection for reduced costs of translational and transcriptional errors. While the large majority of synonymous mutations were deleterious for ribosomal proteins genes, no fitness effects could be detected for the AraCDE genes. Four mutations in AraC and AraE increased fitness, suggesting that slightly advantageous mutations make up a significant fraction of the DFE, but that they often escape detection due to the limited sensitivity of commonly used fitness assays. We show that the fitness effects of amino acid substitutions can be predicted based on evolutionary conservation, but that weakly deleterious mutations are less reliably detected. This suggests that large-effect mutations and the fraction of highly deleterious mutations can be computationally predicted, but that experiments are required to characterize the DFE close to neutrality, where many mutations ultimately fixed in a population will occur.

  • 104.
    Lind, Peter A
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Massey Univ Albany, New Zealand Inst Adv Study, Auckland, New Zealand; Massey Univ Albany, Allan Wilson Ctr Mol Ecol & Evolut, Auckland, New Zealand.
    Farr, Andrew D
    New Zealand Institute for Advanced Study and Allan Wilson Centre for Molecular Ecology and Evolution, Massey University.
    Rainey, Paul B
    New Zealand Institute for Advanced Study and Allan Wilson Centre for Molecular Ecology and Evolution, Massey University; Department of Microbial Population Biology, Max Planck Institute for Evolutionary Biology; Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris-Tech), PSL Research University.
    Evolutionary convergence in experimental Pseudomonas populations2017In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 11, no 3, p. 589-600Article in journal (Refereed)
    Abstract [en]

    Model microbial systems provide opportunity to understand the genetic bases of ecological traits, their evolution, regulation and fitness contributions. Experimental populations of Pseudomonas fluorescens rapidly diverge in spatially structured microcosms producing a range of surface-colonising forms. Despite divergent molecular routes, wrinkly spreader (WS) niche specialist types overproduce a cellulosic polymer allowing mat formation at the air–liquid interface and access to oxygen. Given the range of ways by which cells can form mats, such phenotypic parallelism is unexpected. We deleted the cellulose-encoding genes from the ancestral genotype and asked whether this mutant could converge on an alternate phenotypic solution. Two new traits were discovered. The first involved an exopolysaccharide encoded by pgaABCD that functions as cell–cell glue similar to cellulose. The second involved an activator of an amidase (nlpD) that when defective causes cell chaining. Both types form mats, but were less fit in competition with cellulose-based WS types. Surprisingly, diguanylate cyclases linked to cellulose overexpression underpinned evolution of poly-beta-1,6-N-acetyl-d-glucosamine (PGA)-based mats. This prompted genetic analyses of the relationships between the diguanylate cyclases WspR, AwsR and MwsR, and both cellulose and PGA. Our results suggest that c-di-GMP regulatory networks may have been shaped by evolution to accommodate loss and gain of exopolysaccharide modules facilitating adaptation to new environments.

  • 105.
    Lind, Peter A
    et al.
    New Zealand Institute for Advanced Study, Massey, New; Allan Wilson Centre for Molecular Ecology and Evolution, Massey University, Auckland.
    Farr, Andrew D
    Rainey, Paul B
    Experimental evolution reveals hidden diversity in evolutionary pathways2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e07074Article in journal (Refereed)
    Abstract [en]

    Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans.

  • 106.
    Lindehell, Henrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Kim, Maria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Proximity ligation assays of protein and RNA interactions in the male-specific lethal complex on Drosophila melanogaster polytene chromosomes2015In: Chromosoma, ISSN 0009-5915, E-ISSN 1432-0886, Vol. 124, no 3, p. 385-395Article in journal (Refereed)
    Abstract [en]

    In Drosophila, the male-specific lethal (MSL) complex specifically targets the male X chromosome and participates in a twofold increase in expression output leading to functional dosage compensation. The complex includes five proteins and two non-coding RNAs (ncRNAs). A number of additional associated factors have also been identified. However, the components' roles and interactions have not been fully elucidated. The in situ proximity ligation assay (PLA) provides a sensitive means to determine whether proteins and other factors have bound to chromosomes in close proximity to each other, and thus may interact. Thus, we modified, tested, and applied the assay to probe interactions of MSL complex components on polytene chromosomes. We show that in situ PLA can detect and map both protein-protein and protein-ncRNA interactions on polytene chromosomes at high resolution. We further show that all five protein components of the MSL complex are in close proximity to each other, and the ncRNAs roX1 and roX2 bind the complex in close proximity to MLE. Our results also indicate that JIL1, a histone H3 Ser10 kinase enriched on the male X chromosome, interacts with MSL1 and MSL2, but not MSL3 of the MSL complex. In addition, we corroborate proposed interactions of the MSL complex with both CLAMP and TopoII.

  • 107.
    Lundberg, Lina
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Aneuploidy compensatory mechanisms and genome-wide regulation of gene expression in Drosophila melanogaster2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stimulation or repression of gene expression by genome-wide regulatory mechanisms is an important epigenetic regulatory function which can act to efficiently regulate larger regions or specific groups of genes, for example by compensating for loss or gain of chromosome copy numbers. In Drosophila melanogaster there are two known chromosome-wide regulatory systems; the MSL complex, which mediates dosage compensation of the single male X-chromosome and POF, which stimulates expression from the heterochromatic 4th chromosome. POF also interacts with the heterochromatin inducing protein HP1a, which represses expression from the 4th chromosome but which also has been assigned stimulatory functions. In addition to these two, there is another more elusive and less well-characterized genome-wide mechanism called buffering, which can act to balance transcriptional output of aneuploidy regions of the genome (i.e. copy number variation).

    In my thesis, I describe the presence of a novel physical link between dosage compensation and heterochromatin; mediate by two female-specific POF binding sites, proximal to roX1 and roX2 on the X chromosome (the two non-coding RNAs in the MSL complex). These sites can also provide clues to the mechanisms behind targeting of chromosome-specific proteins. Furthermore, to clarify the conflicting reports about the function of HP1a, I have suggested a mechanism in which HP1a has adopted its function to different genomic locations and gene types. Different binding mechanisms to the promoter vs. the exon of genes allows HP1a to adopt opposite functions; at the promoter, HP1a binding opens up the chromatin structure and stimulates gene expression, whereas the binding to exons condense the chromatin and thus, represses expression. This also causes long genes to be more bound and repressed by HP1a. Moreover, I show that buffering of monosomic regions is a weak but significant response to loss of chromosomal copy numbers, and that this is mediated via a general mechanism which mainly acts on differentially expressed genes, where the effect becomes stronger for long genes. I also show that POF is the factor which compensates for copy number loss of chromosome 4.

  • 108.
    Lundberg, Lina E
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Figueiredo, Margarida L A
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Buffering and proteolysis are induced by segmental monosomy in Drosophila melanogaster2012In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 40, no 13, p. 5926-5937Article in journal (Refereed)
    Abstract [en]

    Variation in the number of individual chromosomes (chromosomal aneuploidy) or chromosome segments (segmental aneuploidy) is associated with developmental abnormalities and reduced fitness in all species examined; it is the leading cause of miscarriages and mental retardation and a hallmark of cancer. However, despite their documented importance in disease, the effects of aneuploidies on the transcriptome remain largely unknown. We have examined the expression effects of seven heterozygous chromosomal deficiencies, both singly and in all pairwise combinations, in Drosophila melanogaster. The results show that genes in one copy are buffered, i.e. expressed more strongly than the expected 50% of wild-type level, the buffering is general and not influenced by other monosomic regions. Furthermore, long genes are significantly more highly buffered than short genes and gene length appears to be the primary determinant of the buffering degree. For short genes the degree of buffering depends on expression level and expression pattern. Furthermore, the results show that in deficiency heterozygotes the expression of genes involved in proteolysis is enhanced and negatively correlates with the degree of buffering. Thus, enhanced proteolysis appears to be a general response to aneuploidy.

  • 109.
    Lundberg, Lina E
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Kim, Maria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Anna-Mia
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Faucillion, Marie-Line
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Josupeit, Rafael
    Division of Tumor Virology, German Cancer Research Center.
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Targeting of Painting of fourth to roX1 and roX2 proximal sites links dosage compensation to heterochromatin in Drosophila melanogasterManuscript (preprint) (Other academic)
    Abstract [en]

    In Drosophila melanogaster, two chromosome‐specific targeting and regulatory systems have been described. The male‐specific lethal (MSL) complex supports dosage compensation by stimulating gene expression from the male X‐chromosome and the protein Painting of fourth (POF) specifically targets and stimulates expression from the heterochromatic 4th chromosome. The targeting sites of both systems are well characterized, but the principles underlying the targeting mechanisms have remained elusive. Here we present an original observation, namely that POF specifically targets two loci on the X‐chromosome, PoX1 and PoX2 (POF‐on‐X). PoX1 and PoX2 are located close to the roX1 and roX2 genes, which encode ncRNAs important for the correct targeting and spreading of the MSL‐complex. We also found that the targeting of POF to PoX1 and PoX2 is largely dependent on roX expression and identified a high‐affinity target region which ectopically recruits POF. The results presented support a model linking the MSL‐complex to POF and dosage compensation to regulation of heterochromatin.

  • 110.
    Lundberg, Lina E
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Kim, Maria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Anna-Mia
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Faucillion, Marie-Line
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Josupeit, Rafael
    German Cancer Research Center (DKFZ).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Targeting of painting of fourth to roX1 and roX2 proximal sites suggests evolutionary links between dosage compensation and the regulation of the 4th chromosome in Drosophila melanogaster2013In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 3, no 8, p. 1325-1334Article in journal (Refereed)
    Abstract [en]

    In Drosophila melanogaster, two chromosome-specific targeting and regulatory systems have been described. The male-specific lethal (MSL) complex supports dosage compensation by stimulating gene expression from the male X-chromosome and the protein Painting of fourth (POF) specifically targets and stimulates expression from the heterochromatic 4(th) chromosome. The targeting sites of both systems are well characterized, but the principles underlying the targeting mechanisms have remained elusive. Here we present an original observation, namely that POF specifically targets two loci on the X-chromosome, PoX1 and PoX2 (POF-on-X). PoX1 and PoX2 are located close to the roX1 and roX2 genes, which encode ncRNAs important for the correct targeting and spreading of the MSL-complex. We also found that the targeting of POF to PoX1 and PoX2 is largely dependent on roX expression and identified a high-affinity target region which ectopically recruits POF. The results presented support a model linking the MSL-complex to POF and dosage compensation to regulation of heterochromatin.

  • 111.
    Lundberg, Lina E
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    HP1a, Su(var)3-9, SETDB1 and POF stimulate or repress gene expression depending on genomic position, gene length and expression pattern in Drosophila melanogaster2013In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 41, no 8, p. 4481-4494Article in journal (Refereed)
    Abstract [en]

    Heterochromatin protein 1a (HP1a) is a chromatin-associated protein important for the formation and maintenance of heterochromatin. In Drosophila, the two histone methyltransferases SETDB1 and Su(var)3-9 mediate H3K9 methylation marks that initiates the establishment and spreading of HP1a-enriched chromatin. Although HP1a is generally regarded as a factor that represses gene transcription, several reports have linked HP1a binding to active genes, and in some cases, it has been shown to stimulate transcriptional activity. To clarify the function of HP1a in transcription regulation and its association with Su(var)3-9, SETDB1 and the chromosome 4-specific protein POF, we conducted genome-wide expression studies and combined the results with available binding data in Drosophila melanogaster. The results suggest that HP1a, SETDB1 and Su(var)3-9 repress genes on chromosome 4, where non-ubiquitously expressed genes are preferentially targeted, and stimulate genes in pericentromeric regions. Further, we showed that on chromosome 4, Su(var)3-9, SETDB1 and HP1a target the same genes. In addition, we found that transposons are repressed by HP1a and Su(var)3-9 and that the binding level and expression effects of HP1a are affected by gene length. Our results indicate that genes have adapted to be properly expressed in their local chromatin environment.

  • 112. Lundberg, Max
    et al.
    Liedvogel, Miriam
    Larson, Keith
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Sigeman, Hanna
    Grahn, Mats
    Wright, Anthony
    Akesson, Susanne
    Bensch, Steffan
    Genetic differences between willow warbler migratory phenotypes are few and cluster in large haplotype blocks2017In: EVOLUTION LETTERS, ISSN 2056-3744, Vol. 1, no 3, p. 155-168Article in journal (Refereed)
    Abstract [en]

    It is well established that differences in migratory behavior between populations of songbirds have a genetic basis but the actual genes underlying these traits remains largely unknown. In an attempt to identify such candidate genes we de novo assembled the genome of the willow warbler Phylloscopus trochilus, and used whole-genome resequencing and a SNP array to associate genomic variation with migratory phenotypes across two migratory divides around the Baltic Sea that separate SW migrating P. t. trochilus wintering in western Africa and SSE migrating P. t. acredula wintering in eastern and southern Africa. We found that the genomes of the two migratory phenotypes lack clear differences except for three highly differentiated regions located on chromosomes 1, 3, and 5 (containing 146, 135, and 53 genes, respectively). Within each migratory phenotype we found virtually no differences in allele frequencies for thousands of SNPs, even when comparing geographically distant populations breeding in Scandinavia and Far East Russia (>6000 km). In each of the three differentiated regions, multidimensional scaling-based clustering of SNP genotypes from more than 1100 individuals demonstrates the presence of distinct haplotype clusters that are associated with each migratory phenotype. In turn, this suggests that recombination is absent or rare between haplotypes, which could be explained by inversion polymorphisms. Whereas SNP alleles on chromosome 3 correlate with breeding altitude and latitude, the allele distribution within the regions on chromosomes 1 and 5 perfectly matches the geographical distribution of the migratory phenotypes. The most differentiated 10 kb windows and missense mutations within these differentiated regions are associated with genes involved in fatty acid synthesis, possibly representing physiological adaptations to the different migratory strategies. The similar to 200 genes in these regions, of which several lack described function, will direct future experimental and comparative studies in the search for genes that underlie important migratory traits.

  • 113. Lutz, Ulrich
    et al.
    Posé, David
    Pfeifer, Matthias
    Gundlach, Heidrun
    Hagmann, Jörg
    Wang, Congmao
    Weigel, Detlef
    Mayer, Klaus F. X.
    Schmid, Markus
    Max Planck Institute for Developmental Biology, Department of Molecular Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
    Schwechheimer, Claus
    Modulation of Ambient Temperature-Dependent Flowering in Arabidopsis thaliana by Natural Variation of FLOWERING LOCUS M2015In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 10, article id e1005588Article in journal (Refereed)
    Abstract [en]

    Plants integrate seasonal cues such as temperature and day length to optimally adjust their flowering time to the environment. Compared to the control of flowering before and after winter by the vernalization and day length pathways, mechanisms that delay or promote flowering during a transient cool or warm period, especially during spring, are less well understood. Due to global warming, understanding this ambient temperature pathway has gained increasing importance. In Arabidopsis thalianaFLOWERING LOCUS M (FLM) is a critical flowering regulator of the ambient temperature pathway. FLM is alternatively spliced in a temperature-dependent manner and the two predominant splice variants, FLM-ß and FLM-δ, can repress and activate flowering in the genetic background of the Athaliana reference accession Columbia-0. The relevance of this regulatory mechanism for the environmental adaptation across the entire range of the species is, however, unknown. Here, we identify insertion polymorphisms in the first intron of FLM as causative for accelerated flowering in many natural A. thaliana accessions, especially in cool (15°C) temperatures. We present evidence for a potential adaptive role of this structural variation and link it specifically to changes in the abundance of FLM-ß. Our results may allow predicting flowering in response to ambient temperatures in the Brassicaceae.

  • 114.
    Ma, Xiao-Fei
    et al.
    Program in Evolutionary Functional Genomics, Evolutionary Biology Center, Uppsala University.
    Hall, David
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    St. Onge, Katherine
    Program in Evolutionary Functional Genomics, Evolutionary Biology Center, Uppsala University.
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Genetic differentiation, clinal variation and phenotypic associations with growth cessation across the Populus tremula Photoperiodic Pathway2010In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 186, p. 1033-1044Article in journal (Refereed)
    Abstract [en]

    Perennial plants monitor seasonal changes through changes inenvironmental conditions such as the quantity and quality oflight. To ensure a correct initiation of critical developmentalprocesses, such as the initiation and cessation of growth, plantshave adapted to a spatially variable light regime and genesin the photoperiodic pathway have been implicated as likelysources for these adaptations. Here we examine genetic variationin genes from the photoperiodic pathway in Populus tremula (Salicaceae)for signatures diversifying selection in response to varyinglight regimes across a latitudinal gradient. We fail to identifyany loci with unusually high levels of genetic differentiationamong populations despite identifying four SNPs that show significantallele frequency clines with latitude. We do, however, observelarge covariance in allelic effects across populations for growthcessation, a highly adaptive trait in P. tremula. High covariancein allelic effects is a signature compatible with diversifyingselection along an environmental gradient. We also observe significantlyhigher heterogeneity in genetic differentiation among SNPs fromthe photoperiod genes than among SNPs from randomly chosen genes.This suggests that spatially variable selection could be affectinggenes from the photoperiod pathway even if selection is notstrong enough to cause individual loci to be identified as outliers.SNPs from three genes in the photoperiod pathway (PHYB2, LHY1,and LHY2) show significant associations with natural variationin growth cessation. Collectively these SNPs explain 10–15%of the phenotypic variation in growth cessation. Covariancesin allelic effects across populations help explain an additional5–7% of the phenotypic variation in growth cessation.

  • 115.
    Mair, Andrea
    et al.
    Vienna, Austria.
    Pedrotti, Lorenzo
    Würzburg, Germany.
    Wurzinger, Bernhard
    Vienna, Austria.
    Anrather, Dorothea
    Vienna, Austria.
    Simeunovic, Andrea
    Vienna, Austria.
    Weiste, Christoph
    Würzburg, Germany.
    Valerio, Concetta
    Oeiras, Portugal.
    Dietrich, Katrin
    Würzburg, Germany.
    Kirchler, Tobias
    Tübingen, Germany.
    Nägele, Thomas
    Vienna, Austria.
    Vicente Carbajosa, Jesús
    Madrid, Spain.
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Molecular Plant Physiology, Utrecht University, Utrecht, The Netherlands.
    Baena-González, Elena
    Oeiras, Portugal.
    Chaban, Christina
    Tübingen, Germany.
    Weckwerth, Wolfram
    Vienna, Austria.
    Dröge-Laser, Wolfgang
    Würzburg, Germany.
    Teige, Markus
    Vienna, Austria.
    SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e05828Article in journal (Refereed)
    Abstract [en]

    Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites.

  • 116. Makarova, Kira S
    et al.
    Wolf, Yuri I
    Alkhnbashi, Omer S
    Costa, Fabrizio
    Shah, Shiraz A
    Saunders, Sita J
    Barrangou, Rodolphe
    Brouns, Stan J J
    Charpentier, Emmanuelle
    Department of Regulation in Infection, Max Planck Institute for Infection Biology.
    Haft, Daniel H
    Horvath, Philippe
    Moineau, Sylvain
    Mojica, Francisco J M
    Terns, Rebecca M
    Terns, Michael P
    White, Malcolm F
    Yakunin, Alexander F
    Garrett, Roger A
    van der Oost, John
    Backofen, Rolf
    Koonin, Eugene V
    An updated evolutionary classification of CRISPR-Cas systems2015In: Nature Reviews Microbiology, ISSN 1740-1526, E-ISSN 1740-1534, Vol. 13, no 11, p. 722-736Article in journal (Refereed)
    Abstract [en]

    The evolution of CRISPR-cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR-cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR-Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized.

  • 117. Mattsson, Åse
    et al.
    Lundstedt, Staffan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stenius, Ulla
    Exposure of HepG2 cells to low levels of PAH-containing extracts from contaminated soils results in unpredictable genotoxic stress responses2009In: Environmental and Molecular Mutagenesis, ISSN 0893-6692, E-ISSN 1098-2280, Vol. 50, no 4, p. 337-348Article in journal (Refereed)
    Abstract [en]

    Contaminated soil is a serious environmental problem, constituting a risk to humans and the environment. Polycyclic aromatic hydrocarbons (PAHs) are often present at contaminated sites. However, risk levels are difficult to estimate because of the complexity of contaminants present. Here, we compare cellular effects of extracts from contaminated soils collected at six industrial settings in Sweden. Chemical analysis showed that all soils contained complex mixtures of PAHs and oxy-PAHs. Western blotting and immunocytochemistry were used to investigate DNA damage signaling in HepG2 cells exposed to extracts from these soils. The effects on phosphorylated Mdm2, p53, Erk, H2AX, 53BP1, and Chk2, cell cycle regulating proteins (cyclin D1 and p21), and cell proliferation were compared. We found that most soil extracts induced phosphorylation of Mdm2 at the 2A10 epitope at low concentrations. This is in line with previous studies suggesting that this endpoint reflects readily repaired DNA-damage. However, we found concentration and time-dependent gamma H2AX and 53BP1 responses that were sustained for 48 hr. These endpoints may reflect the presence of different types of persistent DNA-damage. High concentrations of soil extracts decreased cyclin D1 and increased p21 response, indicating cell cycle arrest. Phosphorylation of Mdm2 at Ser 166, which attenuates the p53 response and is induced by many tumor promoters, was induced in a time-dependent manner and was associated with Erk phosphorylation. Taken together, the PAH extracts elicited unpredictable signaling responses that differed between samples. More polar compounds, i.e., oxy-PAHs, also contributed to the complexity.

  • 118.
    Maurya, Devendra Kumar
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Bohm, Staffan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Alenius, Mattias
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Hedgehog signaling regulates ciliary localization of mouse odorant receptors2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 44, p. E9386-E9394Article in journal (Refereed)
    Abstract [en]

    The ciliary localization of odorant receptors (ORs) is evolutionary conserved and essential for olfactory transduction. However, how the transport of ORs is regulated in mammalian olfactory sensory neurons is poorly understood. Here we demonstrate that odorant responsiveness and OR transport is regulated by the Hedgehog pathway. OR transport is inhibited by conditional gene inactivation of the Hedgehog signal mediator Smoothened (Smo) as well as by systemic administration of the Smo inhibitor vismodegib, a clinically used anticancer drug reported to distort smell perception in patients. The ciliary phenotype of Smo inhibition is haploinsufficient, cell autonomous, and correlates with the accumulation of OR-containing putative transport vesicles in the cytosol. The Smo-dependent OR transport route works in parallel with a low basal transport of vesicle containing both ORs and other olfactory transduction components. These findings both define a physio logical function of Hedgehog signaling in olfaction and provide an important evolutionary link between olfaction and the requirement of a ciliary compartment for Hedgehog signaling.

  • 119.
    Melin, Beatrice S.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nordfjall, Katarina
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    hTERT Cancer Risk Genotypes Are Associated With Telomere Length2012In: Genetic Epidemiology, ISSN 0741-0395, E-ISSN 1098-2272, Vol. 36, no 4, p. 368-372Article in journal (Refereed)
    Abstract [en]

    Telomere biology is associated with cancer initiation and prognosis. Collected data suggest that blood cell telomere length (TL) can change over time, which may be related to development of common disorders, such as cardiovascular diseases and cancer. Recently, single nucleotide polymorphisms in the region of the human telomerase reverse transcriptase (hTERT) gene were associated with various malignancies, including glioma, lung and urinary bladder cancer, and telomerase RNA gene hTERC genotypes were recently linked to TL. In the present study a hypothetical association between identified genotypes in hTERT and hTERC genes and TL were investigated. We analyzed 21 polymorphisms, covering 90% of the genetic variance, in the hTERT gene, two genetic variants in hTERC, and relative TL(RTL) at average age 50 and 60 in 959 individuals with repeated blood samples. Mean RTL at age 60 was associated with four genetic variants of the hTERT gene (rs2736100, rs2853672, rs2853677, and rs2853676), two of which reported to be associated with cancer risk. Two alleles (rs12696304, rs16847897) near the hTERC gene were confirmed as also being associated with RTL at age 60. Our data suggest that hTERT and hTERC genotypes have an impact on TL of potential relevance and detectable first at higher ages, which gives us further insight to the complex regulation of TL. Genet. Epidemiol. 36:368-372, 2012. (c) 2012 Wiley Periodicals, Inc.

  • 120.
    Monroe, Melanie J
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Does competition drive character differences between species on a macroevolutionary scale?2012In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 25, no 11, p. 2341-2347Article in journal (Refereed)
    Abstract [en]

    Sympatric sister species generally have a degree of phenotypic differentiation that allows them to coexist. It has been well documented that phenotypic similarity results, through resource competition, in one of two major outcomes: local extinction of either competitor or character displacement. Limiting similarity suggests that there is a maximum degree of phenotypic niche overlap with which similar species may coexist. Breaching that maximum would result in exclusion. Character displacement, on the other hand, implies that the species differentiate phenotypically so that resource competition is reduced to the point where coexistence is possible. While it has been suggested that these theories have the potential to accelerate (character displacement) or limit phenotypic evolution (competitive exclusion) on microevolutionary time scales, their effects on macroevolution remain under-studied. If competition accelerates evolution on a macroevolutionary scale, one would expect that phenotypic diversity increases as novel species push aside existing species. On the other hand, one might also expect that phenotypic evolution comes to a halt as novel species are trapped in the (ever decreasing) phenotypic space not yet occupied by existing species, except at the extremes of the phenotypic spectrum. Studying the current geographical ranges of more than 3000 extant species representing 29 mammalian families and their respective body masses, I found little evidence of competition accelerating body size differentiation between species.

  • 121.
    Monroe, Melanie J.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Ecology and Genetics, Evolutionary Biology Center, Uppsala University, Uppsala, Sweden.
    Amundsen, T.
    Utne-Palm, A. C.
    Mobley, Kenyon B.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, Plön, Germany.
    Seasonal variation in male alternative reproductive tactics2016In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 29, no 12, p. 2362-2372Article in journal (Refereed)
    Abstract [en]

    Genetic parentage analyses reveal considerable diversity in alternative reproductive behaviours (e.g. sneaking) in many taxa. However, little is known about whether these behaviours vary seasonally and between populations. Here, we investigate seasonal variation in male reproductive behaviours in a population of two-spotted gobies (Gobiusculus flavescens) in Norway. Male two-spotted gobies guard nests, attract females and care for fertilized eggs. We collected clutches and nest-guarding males early and late in the breeding season in artificial nests and used microsatellite markers to reconstruct parentage from a subset of offspring from each nest. We hypothesized that mating, reproductive success and sneaking should be more prevalent early in the breeding season when competition for mates among males is predicted to be higher. However, parentage analyses revealed similar values of mating, reproductive success and high frequencies of successful sneaking early (30% of nests) and late (27% of nests) in the season. We also found that multiple females with eggs in the same nest were fertilized by one or more sneaker males, indicating that some males in this population engage in a satellite strategy. We contrast our results to previous work that demonstrates low levels of cuckoldry in a population in Sweden. Our results demonstrate marked stability in both the genetic mating system and male alternative reproductive tactics over the breeding season. However, sneaking rates may vary geographically within a species, likely due to local selection influencing ecological factors encountered at different locations.

  • 122.
    Moreno, Renata
    et al.
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Zafra, Olga
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Cava, Felipe
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Berenguer, José
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Development of a gene expression vector for Thermus thermophilus based on the promoter of the respiratory nitrate reductase2003In: Plasmid, ISSN 0147-619X, E-ISSN 1095-9890, Vol. 49, no 1, p. 2-8Article in journal (Refereed)
    Abstract [en]

    A specific expression system for Thermus spp. is described. Plasmid pMKE1 contains replicative origins for Escherichia coli and Thermus spp., a selection gene encoding a thermostable resistance to kanamycin, and a 720 bp DNA region containing the promoter (Pnar), and the regulatory sequences of the respiratory nitrate reductase operon of Thermus thermophilus HB8. Two genes, encoding a thermophilic beta-galactosidase and an alkaline phosphatase were cloned in pMKE1 as cytoplasmic and periplasmic reporters, respectively. The expression of the reporters was specifically induced by the combined action of nitrate and anoxia in facultative anaerobic derivatives of T. thermophilus HB27 to which the gene cluster for nitrate respiration was transferred by conjugation. Overexpressions in the range of approximately 200-fold were obtained for the cytoplasmic reporter, whereas that of the periplasmic reporter was limited to approximately 20-fold, with respect to their intrinsic respective activities.

  • 123. Mosing, Miriam
    et al.
    Johannesson, Magnus
    Madison, Guy
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Magnusson, Patrik
    Cesarini, David
    Nakamura, Jeanne
    Pedersen, Nancy
    Ullen, Fredrik
    Genetic influences on flow proneness and its relationship to behavioral inhibition and locus of control2012In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 42, no 6, p. 956-956Article in journal (Other academic)
  • 124. Mosing, Miriam
    et al.
    Madison, Guy
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Pedersen, Nancy
    Ullén, Fredrik
    Genetic and environmental influences on the relationship between different measures of music ability and IQ2013In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 43, no 6, p. 533-533Article in journal (Other academic)
  • 125. Moussy, Caroline
    et al.
    Arlettaz, Raphaël
    Copete, José Luis
    Dale, Svein
    Dombrovski, Valery
    Elts, Jaanus
    Lorrillière, Romain
    Marja, Riho
    Pasquet, Eric
    Piha, Markus
    Seimola, Tuomas
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Agricultural Research in Northern Sweden, Swedish University of Agricultural Sciences.
    Selstam, Gunnar
    Jiguet, Frédéric
    The genetic structure of the European breeding populations of a declining farmland bird, the ortolan bunting (Emberiza hortulana), reveals conservation priorities2018In: Conservation Genetics, ISSN 1566-0621, E-ISSN 1572-9737, Vol. 19, no 4, p. 909-922Article in journal (Refereed)
    Abstract [en]

    Anthropogenic activities, such as agricultural intensification, caused large declines in biodiversity, including farmland birds. In addition to demographic consequences, anthropogenic activities can result in loss of genetic diversity, reduction of gene flow and altered genetic structure. We investigated the distribution of the genetic variation of a declining farmland and long-distance migratory bird, the ortolan bunting Emberiza hortulana, across its European breeding range to assess the impact of human-driven population declines on genetic diversity and structure in order to advise conservation priorities. The large population declines observed have not resulted in dramatic loss of genetic diversity, which is moderate to high and constant across all sampled breeding sites. Extensive gene flow occurs across the breeding range, even across a migratory divide, which contributes little to genetic structuring. However, gene flow is asymmetric, with the large eastern populations acting as source populations for the smaller western ones. Furthermore, breeding populations that underwent the largest declines, in Fennoscandia and Baltic countries, appear to be recently isolated, with no gene exchange occurring with the eastern or the western populations. These are signs for concern as declines in the eastern populations could affect the strength of gene flow and in turn affect the western populations. The genetic, and demographic, isolation of the northern populations make them particularly sensitive to loss of genetic diversity and to extinction as no immigration is occurring to counter-act the drastic declines. In such a situation, conservation efforts are needed across the whole breeding range: in particular, protecting the eastern populations due to their key role in maintaining gene flow across the range, and focussing on the northern populations due to their recent isolation and endangered status.

  • 126. Neale, David B
    et al.
    Ingvarsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Population, quantitative and comparative genomics of adaptation in forest trees2008In: Current opinion in plant biology, ISSN 1369-5266, E-ISSN 1879-0356, Vol. 11, no 2, p. 149-155Article in journal (Refereed)
    Abstract [en]

    High-throughput DNA sequencing and genotyping technologies have enabled a new generation of research in plant genetics where combined quantitative and population genetic approaches can be used to better understand the relationship between naturally occurring genotypic and phenotypic diversity. Forest trees are highly amenable to such studies because of their combined undomesticated and partially domesticated state. Forest geneticists are using association genetics to dissect complex adaptive traits and discover the underlying genes. In parallel, they are using resequencing of candidate genes and modern population genetics methods to discover genes under natural selection. This combined approach is identifying the most important genes that determine patterns of complex trait adaptation observed in many tree populations.

  • 127.
    Netotea, Sergiu
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Sundell, David
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    ComPlEx: conservation and divergence of co-expression networks in A. thaliana, Populus and O. sativa2014In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, p. 106-Article in journal (Refereed)
    Abstract [en]

    Background: Divergence in gene regulation has emerged as a key mechanism underlying species differentiation. Comparative analysis of co-expression networks across species can reveal conservation and divergence in the regulation of genes. Results: We inferred co-expression networks of A. thaliana, Populus spp. and O. sativa using state-of-the-art methods based on mutual information and context likelihood of relatedness, and conducted a comprehensive comparison of these networks across a range of co-expression thresholds. In addition to quantifying gene-gene link and network neighbourhood conservation, we also applied recent advancements in network analysis to do cross-species comparisons of network properties such as scale free characteristics and gene centrality as well as network motifs. We found that in all species the networks emerged as scale free only above a certain co-expression threshold, and that the high-centrality genes upholding this organization tended to be conserved. Network motifs, in particular the feed-forward loop, were found to be significantly enriched in specific functional subnetworks but where much less conserved across species than gene centrality. Although individual gene-gene co-expression had massively diverged, up to similar to 80% of the genes still had a significantly conserved network neighbourhood. For genes with multiple predicted orthologs, about half had one ortholog with conserved regulation and another ortholog with diverged or non-conserved regulation. Furthermore, the most sequence similar ortholog was not the one with the most conserved gene regulation in over half of the cases. Conclusions: We have provided a comprehensive analysis of gene regulation evolution in plants and built a web tool for Comparative analysis of Plant co-Expression networks (ComPlEx, http:// complex. plantgenie. org/). The tool can be particularly useful for identifying the ortholog with the most conserved regulation among several sequence-similar alternatives and can thus be of practical importance in e. g. finding candidate genes for perturbation experiments.

  • 128.
    Nordström, Stefan
    Umeå University, Faculty of Science and Technology.
    Genealogi och genetik: Beskrivning av sex projektområden där kyrkböcker använts i genetisk forskning1991Report (Other academic)
  • 129.
    Nordström, Stefan
    Umeå University, Faculty of Science and Technology.
    Genealogical and genetical studies of hereditary macular degeneration in the county of Västerbotten, Sweden1974Doctoral thesis, comprehensive summary (Other academic)
  • 130.
    Nordström, Stefan
    Umeå University.
    Livets trådar - livets väv2003In: Scriptum : rapportserie / utg. av Forskningsarkivet vid Umeå universitet, ISSN 0284-3161, Vol. 52, p. 62-67Article in journal (Other academic)
  • 131.
    Norman, Anita J.
    et al.
    Sveriges lantbruksuniversitet.
    Street, Nathaniel Robert
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Spong, Goran
    Sveriges lantbruksuniversitet.
    De Novo SNP Discovery in the Scandinavian Brown Bear (Ursus arctos)2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. e81012-Article in journal (Refereed)
    Abstract [en]

    Information about relatedness between individuals in wild populations is advantageous when studying evolutionary, behavioural and ecological processes. Genomic data can be used to determine relatedness between individuals either when no prior knowledge exists or to confirm suspected relatedness. Here we present a set of 96 SNPs suitable for inferring relatedness for brown bears (Ursus arctos) within Scandinavia. We sequenced reduced representation libraries from nine individuals throughout the geographic range. With consensus reads containing putative SNPs, we applied strict filtering criteria with the aim of finding only high-quality, highly-informative SNPs. We tested 150 putative SNPs of which 96% were validated on a panel of 68 individuals. Ninety-six of the validated SNPs with the highest minor allele frequency were selected. The final SNP panel includes four mitochondrial markers, two monomorphic Y-chromosome sex-determination markers, three X-chromosome SNPs and 87 autosomal SNPs. From our validation sample panel, we identified two previously known parent-offspring dyads with reasonable accuracy. This panel of SNPs is a promising tool for inferring relatedness in the brown bear population in Scandinavia.

  • 132.
    Norregaard, Kamilla
    et al.
    The Niels Bohr Institute.
    Andersson, Magnus
    Umeå University, Faculty of Science and Technology, Department of Physics. Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
    Nielsen, Peter
    Department of Cellular and Molecular Medicine, Faculty of Health and Sciences, University of Copenhagen, Copenhagen, Denmark.
    Brown, Stanley
    Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark .
    Oddershede, Lene
    Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
    Tethered particle analysis of supercoiled circular DNA using PNA handles2014In: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 9, no 9, p. 2206-2223Article in journal (Refereed)
  • 133.
    Obudulu, Ogonna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bygdell, Joakim
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sundberg, Bjorn
    Moritz, Thomas
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. 5 Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Norway.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wingsle, Gunnar
    Quantitative proteomics reveals protein profiles underlying major transitions in aspen wood development2016In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 17, article id 119Article in journal (Refereed)
    Abstract [en]

    Background: Wood development is of outstanding interest both to basic research and industry due to the associated cellulose and lignin biomass production. Efforts to elucidate wood formation (which is essential for numerous aspects of both pure and applied plant science) have been made using transcriptomic analyses and/or low-resolution sampling. However, transcriptomic data do not correlate perfectly with levels of expressed proteins due to effects of post-translational modifications and variations in turnover rates. In addition, high-resolution analysis is needed to characterize key transitions. In order to identify protein profiles across the developmental region of wood formation, an in-depth and tissue specific sampling was performed. Results: We examined protein profiles, using an ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry system, in high-resolution tangential sections spanning all wood development zones in Populus tremula from undifferentiated cambium to mature phloem and xylem, including cell expansion and cell death zones. In total, we analyzed 482 sections, 20-160 mu m thick, from four 47-year-old trees growing wild in Sweden. We obtained high quality expression profiles for 3,082 proteins exhibiting consistency across the replicates, considering that the trees were growing in an uncontrolled environment. A combination of Principal Component Analysis (PCA), Orthogonal Projections to Latent Structures (OPLS) modeling and an enhanced stepwise linear modeling approach identified several major transitions in global protein expression profiles, pinpointing (for example) locations of the cambial division leading to phloem and xylem cells, and secondary cell wall formation zones. We also identified key proteins and associated pathways underlying these developmental landmarks. For example, many of the lignocellulosic related proteins were upregulated in the expansion to the early developmental xylem zone, and for laccases with a rapid decrease in early xylem zones. We observed upregulation of two forms of xylem cysteine protease (Potri.002G005700.1 and Potri.005G256000.2; Pt-XCP2.1) in early xylem and their downregulation in late maturing xylem. Our data also show that Pt-KOR1.3 (Potri.003G151700.2) exhibits an expression pattern that supports the hypothesis put forward in previous studies that this is a key xyloglucanase involved in cellulose biosynthesis in primary cell walls and reduction of cellulose crystallinity in secondary walls. Conclusion: Our novel multivariate approach highlights important processes and provides confirmatory insights into the molecular foundations of wood development.

  • 134. Oei, Ling
    et al.
    Hsu, Yi-Hsiang
    Styrkarsdottir, Unnur
    Eussen, Bert H
    de Klein, Annelies
    Peters, Marjolein J
    Halldorsson, Bjarni
    Liu, Ching-Ti
    Alonso, Nerea
    Kaptoge, Stephen K
    Thorleifsson, Gudmar
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hocking, Lynne J
    Husted, Lise Bjerre
    Jameson, Karen A
    Kruk, Marcin
    Lewis, Joshua R
    Patel, Millan S
    Scollen, Serena
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Trompet, Stella
    van Schoor, Natasja M
    Zhu, Kun
    Buckley, Brendan M
    Cooper, Cyrus
    Ford, Ian
    Goltzman, David
    González-Macías, Jesús
    Langdahl, Bente Lomholt
    Leslie, William D
    Lips, Paul
    Lorenc, Roman S
    Olmos, José M
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Reid, David M
    Riancho, José A
    Slagboom, P Eline
    Garcia-Ibarbia, Carmen
    Ingvarsson, Thorvaldur
    Johannsdottir, Hrefna
    Luben, Robert
    Medina-Gómez, Carolina
    Arp, Pascal
    Nandakumar, Kannabiran
    Palsson, Stefan Th
    Sigurdsson, Gunnar
    van Meurs, Joyce B J
    Zhou, Yanhua
    Hofman, Albert
    Jukema, J Wouter
    Pols, Huibert A P
    Prince, Richard L
    Cupples, L Adrienne
    Marshall, Christian R
    Pinto, Dalila
    Sato, Daisuke
    Scherer, Stephen W
    Reeve, Jonathan
    Thorsteinsdottir, Unnur
    Karasik, David
    Richards, J Brent
    Stefansson, Kari
    Uitterlinden, André G
    Ralston, Stuart H
    Ioannidis, John P A
    Kiel, Douglas P
    Rivadeneira, Fernando
    Estrada, Karol
    A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus2014In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 51, no 2, p. 122-131Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.

    AIM: To identify CNVs associated with osteoporotic bone fracture risk.

    METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.

    RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.

    CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

  • 135.
    Olofsson, Jonas
    et al.
    Stockholms universitet.
    Örestig, Johan
    Umeå University, Faculty of Social Sciences, Department of Education.
    Evolutionsteori och människans natur2015Book (Other academic)
  • 136.
    Olsson, Jenny
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Genetic diversity and hardiness in Scots pine from Scandinavia to Russia2019Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    The postglacial recolonization of northern Europe supposedly originated from Western Europe and the Russian Plain, however, recent molecular and macrofossil-based investigations suggest that the history may be more complex than previously thought. This study aims to investigate the genetic diversity and population structure of Scots pine from Scandinavia to Russia to re-evaluate its recolonization history, and to examine whether the pattern of spatial genetic diversity has any adaptive significance. Populations ranging from Norway to Russia were sampled and genotyped using genotyping-by-sequencing. The seedlings were freeze tested to provide an average degree of hardiness for every population. Eight hundred and thirty-two seedlings were analyzed, and 6,034 SNPs were recovered in these individuals after stringent filtering. Population structure was investigated using fastStructure and differentiation between populations was estimated with pairwise FST and analysis of molecular variance (AMOVA) to assess the genetic variability. Genetic diversity was measured as observed heterozygosity, H0, in populations, clusters and overall. Two genetic clusters were detected in the samples, one in Norway and Sweden and one in Russia. These clusters are weakly differentiated (FST = 0.01202) with only 0.66 % variation between them. Highest variation was found within populations (98.8 %) and the overall genetic diversity for all populations was high (Ho = 0.2573). The weak differentiation and high diversity are indicative of extensive gene flow between populations in this species. The composition of the clusters across the sampled area suggests a westward recolonization from the Russian Plain into Scandinavia, and a possible local origin of another polymorphism in Norway and Sweden. No clear relationship between cold hardiness and genetic variation was detected. The clinal variation in cold hardiness reflects local adaptation, and the difference between genetic and phenotypic variation is likely due to epigenetic regulation or polygenic inheritance. More extensive genome scan is needed to understand the genetic basis of local adaptation.

  • 137.
    Pacurar, Daniel Ioan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Pacurar, Monica Lacramioara
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Bussell, John Desmond
    Pop, Tiberia Ioana
    Gutierrez, Laurent
    Bellini, Catherine
    A collection of INDEL markers for map-based cloning in seven Arabidopsis accessions2012In: Journal of Experimental Botany, ISSN 0022-0957, E-ISSN 1460-2431, Vol. 63, no 7, p. 2491-2501Article in journal (Refereed)
    Abstract [en]

    The availability of a comprehensive set of resources including an entire annotated reference genome, sequenced alternative accessions, and a multitude of marker systems makes Arabidopsis thaliana an ideal platform for genetic mapping. PCR markers based on INsertions/DELetions (INDELs) are currently the most frequently used polymorphisms. For the most commonly used mapping combination, ColumbiaxLandsberg erecta (Col-0xLer-0), the Cereon polymorphism database is a valuable resource for the generation of polymorphic markers. However, because the number of markers available in public databases for accessions other than Col-0 and Ler-0 is extremely low, mapping using other accessions is far from straightforward. This issue arose while cloning mutations in the Wassilewskija (Ws-4) background. In this work, approaches are described for marker generation in Ws-4 x Col-0. Complementary strategies were employed to generate 229 INDEL markers. Firstly, existing Col-0/Ler-0 Cereon predicted polymorphisms were mined for transferability to Ws-4. Secondly, Ws-0 ecotype Illumina sequence data were analyzed to identify INDELs that could be used for the development of PCR-based markers for Col-0 and Ws-4. Finally, shotgun sequencing allowed the identification of INDELs directly between Col-0 and Ws-4. The polymorphism of the 229 markers was assessed in seven widely used Arabidopsis accessions, and PCR markers that allow a clear distinction between the diverged Ws-0 and Ws-4 accessions are detailed. The utility of the markers was demonstrated by mapping more than 35 mutations in a Col-0xWs-4 combination, an example of which is presented here. The potential contribution of next generation sequencing technologies to more traditional map-based cloning is discussed.

  • 138.
    Papageorgiou, Aristotelis C.
    et al.
    Department of Forestry, Environment and Natural Resources, Democritus University of Thrace, Orestiada, Greece.
    Vidalis, Amaryllis
    Department of Forestry, Environment and Natural Resources, Democritus University of Thrace, Orestiada, Greece.
    Gailing, Oliver
    Institut für Forstgenetik und Forstpflanzenzüchtung, Georg-August-Universität Göttingen, Göttingen, Germany.
    Tsiripidis, Ioannis
    Biology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece .
    Hatziskakis, Seraphim
    Department of Forestry, Environment and Natural Resources, Democritus University of Thrace, Orestiada, Greece.
    Boutsios, Stefanos
    Department of Forestry, Environment and Natural Resources, Democritus University of Thrace, Orestiada, Greece .
    Galatsidas, Spiros
    Department of Forestry, Technical Educational Institute of Kavala, Drama, Greece .
    Finkeldey, Reiner
    Institut für Forstgenetik und Forstpflanzenzüchtung, Georg-August-Universität Göttingen, Göttingen, Germany.
    Genetic variation of beech (Fagus sylvatica L.) in Rodopi (NE Greece)2008In: European Journal of Forest Research, ISSN 1612-4669, E-ISSN 1612-4677, Vol. 127, no 1, p. 81-88Article in journal (Refereed)
    Abstract [en]

    The recent taxonomic classification of beech in Europe considers existence of one species (Fagus sylvatica L.) with two subspecies: F. sylvatica ssp. sylvatica and F. sylvatica ssp. orientalis. Four beech populations growing on the Greek part of the Rodopi Mountains were studied using morphological traits as well as DNA molecular markers (AFLPs and chloroplast DNA SSR). The aim of the study was to describe the variation patterns of beech in the Rodopi Mountains and to test the hypothesis of possible introgression between the beech subspecies' sylvatica and orientalis in this area. Both morphological traits and gene markers revealed a possible influence of F. orientalis on the east side of Rodopi and at the low elevations, while characters resembling F. sylvatica were observed mainly on the western part of the mountains and in higher altitudes. There was a clinal increase of genetic diversity from the west to the east, reaching a level firstly reported for beech populations. These results can be explained either by the existence of a main refugial area for beech during the last glaciation or by the occurrence of a recent hybridization among the subspecies, which were spatially isolated during the last glaciation and came into reproductive contact during their postglacial remigration. These two scenarios are not necessarily mutually exclusive.

  • 139.
    Philip, Philge
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Mining DNA elements involved in targeting of chromatin modifiers2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: In all higher organisms, the nuclear DNA is condensed into nucleosomes that consist of DNA wrapped around a core of highly conserved histone proteins. DNA bound to histones and other structural proteins form the chromatin. Generally, only few regions of DNA are accessible and most of the time RNA polymerase and other DNA binding proteins have to overcome this compaction to initiate transcription. Several proteins are involved in making the chromatin more compact or open. Such chromatin-modifying proteins make distinct post-translational modifications of histones – especially in the histone tails – to alter their affinity to DNA. Aim: The main aim of my thesis work is to study the targeting of chromatin modifiers important for correct gene expression in Drosophila melanogaster (fruit flies). Primary DNA sequences, chromatin associated proteins, transcription, and non-coding RNAs are all likely to be involved in targeting mechanisms. This thesis work involves the development of new computational methods for identification of DNA motifs and protein factors involved in the targeting of chromatin modifiers. Targeting and functional analysis of two chromatin modifiers, namely male-specific lethal (MSL) complex and CREB-binding protein (CBP) are specifically studied. The MSL complex is a protein complex that mediates dosage compensation in flies. CBP protein is known as a transcriptional co-regulator in metazoans and it has histone acetyl transferase activity and CBP has been used to predict novel enhancers. Results: My studies of the binding sites of MSL complex shows that promoters and coding sequences of MSL-bound genes on the X-chromosome of Drosophila melanogaster can influence the spreading of the complex along the X-chromosome. Analysis of MSL binding sites when two non-coding roX RNAs are mutated shows that MSL-complex recruitment to high-affinity sites on the Xchromosome is independent of roX, and the role of roX RNAs is to prevent binding to repeats in autosomal sites. Functional analysis of MSL-bound genes using their dosage compensation status shows that the function of the MSL complex is to enhance the expression of short housekeeping genes, but MSL-independent mechanisms exist to achieve complete dosage compensation. Studies of the binding sites of the CBP protein show that, in early embryos, Dorsal in cooperation with GAGA factor (GAF) and factors like Medea and Dichaete target CBP to its binding sites. In the S2 cell line, GAF is identified as the targeting factor of CBP at promoters and enhancers, and GAF and CBP together are found to induce high levels of polymerase II pausing at promoters. In another study using integrated data analysis, CBP binding sites could be classified into polycomb protein binding sites, repressed enhancers, insulator protein-bound regions, active promoters, and active enhancers, and this suggested different potential roles for CBP. A new approach was also developed to eliminate technical bias in skewed experiments. Our study shows that in the case of skewed datasets it is always better to identify non-altered variables and to normalize the data using only such variables.

  • 140.
    Philip, Philge
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Computational Life Science Cluster (CLiC), Umeå University, Sweden.
    Boija, Ann
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden.
    Mannervik, Mattias
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Computational Life Science Cluster (CLiC), Umeå University, Sweden.
    CBP functions outside of promoters and enhancers in Drosophila melanogasterManuscript (preprint) (Other academic)
  • 141.
    Philip, Philge
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Pettersson, Fredrik
    Umbio, 907 19 Umeå, Sweden.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Sequence signatures involved in targeting the male-specific lethal complex to X-chromosomal genes in Drosophila melanogaster2012In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, p. 97-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In Drosophila melanogaster, the dosage-compensation system that equalizes X-linked gene expression between males and females, thereby assuring that an appropriate balance is maintained between the expression of genes on the X chromosome(s) and the autosomes, is at least partially mediated by the Male-Specific Lethal (MSL) complex. This complex binds to genes with a preference for exons on the male X chromosome with a 3' bias, and it targets most expressed genes on the X chromosome. However, a number of genes are expressed but not targeted by the complex. High affinity sites seem to be responsible for initial recruitment of the complex to the X chromosome, but the targeting to and within individual genes is poorly understood.

    RESULTS: We have extensively examined X chromosome sequence variation within five types of gene features (promoters, 5' UTRs, coding sequences, introns, 3' UTRs) and intergenic sequences, and assessed its potential involvement in dosage compensation. Presented results show that: the X chromosome has a distinct sequence composition within its gene features; some of the detected variation correlates with genes targeted by the MSL-complex; the insulator protein BEAF-32 preferentially binds upstream of MSL-bound genes; BEAF-32 and MOF co-localizes in promoters; and that bound genes have a distinct sequence composition that shows a 3' bias within coding sequence.

    CONCLUSIONS: Although, many strongly bound genes are close to a high affinity site neither our promoter motif nor our coding sequence signatures show any correlation to HAS. Based on the results presented here, we believe that there are sequences in the promoters and coding sequences of targeted genes that have the potential to direct the secondary spreading of the MSL-complex to nearby genes.

  • 142.
    Philip, Philge
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Male X-linked genes in Drosophila melanogaster are compensated independently of the Male-Specific Lethal complex2013In: Epigenetics & Chromatin, ISSN 1756-8935, E-ISSN 1756-8935, Vol. 6, no Article number: 35Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In organisms where the two sexes have unequal numbers of X-chromosomes, the expression of X-linked genes needs to be balanced not only between the two sexes, but also between X and the autosomes. In Drosophila melanogaster, the Male-Specific Lethal (MSL) complex is believed to produce a 2-fold increase in expression of genes on the male X, thus restoring this balance.

    RESULTS: Here we show that almost all the genes on the male X are effectively compensated. However, many genes are compensated without any significant recruitment of the MSL-complex. These genes are very weakly, if at all, affected by mutations or RNAi against MSL-complex components. In addition, even the genes that are strongly bound by MSL rely on mechanisms other than the MSL-complex for proper compensation. We find that long, non-ubiquitously expressed genes tend to rely less on the MSL-complex for their compensation and genes that in addition are far from High Affinity Sites tend to not bind the complex at all or very weakly.

    CONCLUSIONS: We conclude that most of the compensation of X-linked genes is produced by an MSL-independent mechanism. Similar to the case of the MSL-mediated compensation we do not yet know the mechanism behind the MSL-independent compensation that appears to act preferentially on long genes. Even if we observe similarities, it remains to be seen if the mechanism is related to the buffering that is observed in autosomal aneuploidies.

  • 143. Pontarp, Mikael
    et al.
    Bunnefeld, Lynsey
    Cabral, Juliano Sarmento
    Etienne, Rampal S.
    Fritz, Susanne A.
    Gillespie, Rosemary
    Graham, Catherine H.
    Hagen, Oskar
    Hartig, Florian
    Huang, Shan
    Jansson, Roland
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Maliet, Odile
    Münkemüller, Tamara
    Pellissier, Loïc
    Rangel, Thiago F.
    Storch, David
    Wiegand, Thorsten
    Hurlbert, Allen H.
    The Latitudinal Diversity Gradient: Novel Understanding through Mechanistic Eco-evolutionary2019In: Trends in Ecology & Evolution, ISSN 0169-5347, E-ISSN 1872-8383, Vol. 34, no 3, p. 211-223Article, review/survey (Refereed)
    Abstract [en]

    The latitudinal diversity gradient (LDG) is one of the most widely studied patterns in ecology, yet no consensus has been reached about its underlying causes. We argue that the reasons for this are the verbal nature of existing hypotheses, the failure to mechanistically link interacting ecological and evolutionary processes to the LDG, and the fact that empirical patterns are often consistent with multiple explanations. To address this issue, we synthesize current LDG hypotheses, uncovering their eco-evolutionary mechanisms, hidden assumptions, and commonalities. Furthermore, we propose mechanistic eco-evolutionary modeling and an inferential approach that makes use of geographic, phylogenetic, and trait-based patterns to assess the relative importance of different processes for generating the LDG.

  • 144. Rainey, Paul B.
    et al.
    Remigi, Philippe
    Farr, Andrew D.
    Lind, Peter A.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Darwin was right: where now for experimental evolution?2017In: Current Opinion in Genetics and Development, ISSN 0959-437X, E-ISSN 1879-0380, Vol. 47, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Over the last two decades interest in direct realisation of evolutionary process and the possibilities presented by real time evolution experiments with microbes have escalated. Long-term selection experiments with bacteria have made increasingly transparent the process of evolution by natural selection. In this short article we consider what next for the field and do so by highlighting two areas of interest: the genotype-to-phenotype map and the constraints it imposes on evolution, and studies on major evolutionary transitions and in particular the importance of selection working over more than one timescale. The latter we discuss in light of new technologies that allow imposition of Darwinian properties on populations and communities and how this allows exploration of new avenues of research. We conclude by commenting on microbial communities and the operation of evolutionary processes that are likely intrinsic — and specific — to communities.

  • 145. Randall, Ricardo S.
    et al.
    Miyashima, Shunsuke
    Blomster, Tiina
    Zhang, Jing
    Elo, Annakaisa
    Karlberg, Anna
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Immanen, Juha
    Nieminen, Kaisa
    Lee, Ji-Young
    Kakimoto, Tatsuo
    Blajecka, Karolina
    Melnyk, Charles W.
    Alcasabas, Annette
    Forzani, Celine
    Matsumoto-Kitano, Miho
    Maehoenen, Ari Pekka
    Bhalerao, Rishikesh
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Dewitte, Walter
    Helariutta, Ykae
    Murray, James A. H.
    AINTEGUMENTA and the D-type cyclin CYCD3;1 regulate root secondary growth and respond to cytokinins2015In: Biology Open, ISSN 2046-6390, Vol. 4, no 10, p. 1229-1236Article in journal (Refereed)
    Abstract [en]

    Higher plant vasculature is characterized by two distinct developmental phases. Initially, a well-defined radial primary pattern is established. In eudicots, this is followed by secondary growth, which involves development of the cambium and is required for efficient water and nutrient transport and wood formation. Regulation of secondary growth involves several phytohormones, and cytokinins have been implicated as key players, particularly in the activation of cell proliferation, but the molecular mechanisms mediating this hormonal control remain unknown. Here we show that the genes encoding the transcription factor AINTEGUMENTA (ANT) and the D-type cyclin CYCD3;1 are expressed in the vascular cambium of Arabidopsis roots, respond to cytokinins and are both required for proper root secondary thickening. Cytokinin regulation of ANT and CYCD3 also occurs during secondary thickening of poplar stems, suggesting this represents a conserved regulatory mechanism.

  • 146.
    Rasmuson, Marianne
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Trends in genetics - before the molecular era2010In: Hereditas, ISSN 0018-0661, E-ISSN 1601-5223, Vol. 147, no 5, p. 243-249Article in journal (Refereed)
    Abstract [en]

    Genetics grew into a scientific discipline during the first decade of the twentieth century, it prospered and became acknowledged in its first half, it widened into the molecular field during its second half. This expansion attracted scientists from nearby branches such as biochemistry, biophysics, cell biology, statistics and computer science, which started to call themselves geneticists without deeper insights into the classical genetics. They may be unaware of how far the science had advanced already before the molecular window was opened. Then, what is the essence of genetics? It is involved in all aspects of biology, and has branched into different disciplines, rather far apart. Still it is held together by its core, the evolutionary coalescence of all living organisms on earth and their surprisingly great conformity in physiological and hereditary mechanisms. In the early definitions before the year 1900 the word variation is often included, most bluntly as the science of variation. Similarities and differences between parent and offspring are also emphasised. Inheritance causes similarities but not complete likeness. The name of the subject, genetics, was introduced by W. Bateson in 1906 and defined as the scientific study of the heredity of individuals. Later definitions have become more extensive and include not only the transmission of the hereditary factors but also their nature and the way in which they influence the living organism at different stages and at different levels, from molecules to populations and ecosystems.

  • 147. Raychaudhuri, Saumya
    et al.
    Jain, Vibhu
    Dongre, Mitesh
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Identification of a constitutively active variant of LuxO that affects production of HA/protease and biofilm development in a non-O1, non-O139 Vibrio cholerae O110.2006In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 369, p. 126-33Article in journal (Refereed)
    Abstract [en]

    Pathogenesis of Vibrio cholerae depends on the concerted action of numerous virulence factors that includes a secreted hemagglutinin (HA) protease. Recent studies have evidenced that the expression of these virulence factors as well as the genes responsible for biofilm development is subject to control by quorum sensing in this organism. At low cell density, LuxO, the pivotal regulator of quorum-sensing circuit, has been shown to be phosphorylated at aspartate-47. Working in concert with sigma-54, LuxO-P activates the downstream repressor, which turned out to be four sRNAs [Lenz, D.H., Mok, K.C., Lilley, B.N., Kulkarni, R.V., Wingreen, N.S., Bassler, B.L., 2004. The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118, 69-82]. Subsequently, these sRNAs form complex with sRNA chaperone, Hfq. The Hfq-sRNA complex causes the destabilization of hapR mRNA transcript. HapR is a positive regulator of hapA that encodes HA/protease. At high cell density, dephosphorylation of LuxO impairs its function to activate the expression of sRNA, which in turn promotes HapR expression and causes protease production. It has been demonstrated that conversion of aspartate to glutamate (D47E) renders the LuxO molecule active without being phosphorylated. This variant of LuxO is referred as constitutively active LuxO or con-LuxO [Freeman, J.A., Bassler, B.L., 1999. A genetic analysis of the function of LuxO, a two-component response regulator involved in quorum sensing in Vibrio harveyi. Mol Microbiol 31, 665-677]. Other than D47E, mutation at L104Q also develops con-LuxO [Vance, R.E., Zhu, J., Mekalanos, J.J., 2003. A constitutively active variant of the quorum-sensing regulator LuxO affects protease production and biofilm formation in Vibrio cholerae. Infect. Immun. 71, 2571-2576]. The purpose of this study was to investigate the cause of protease negative phenotype of a non-O1, non-O139 strain of V. cholerae O110. In the process of exploring the nature of the phenotype, a constitutively active variant of LuxO molecule was characterized which represses protease production and enhances biofilm formation by this strain. Unlike luxU, disruption of luxO restored the protease production, which showed the constitutively active nature of LuxO protein in this strain.

  • 148. Robertson, Fiona M.
    et al.
    Gundappa, Manu Kumar
    Grammes, Fabian
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Redmond, Anthony K.
    Lien, Sigbjørn
    Martin, Samuel A. M.
    Holland, Peter W. H.
    Sandve, Simen R.
    Macqueen, Daniel J.
    Lineage-specific rediploidization is a mechanism to explain time-lags between genome duplication and evolutionary diversification2017In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 18, article id 111Article in journal (Refereed)
    Abstract [en]

    Background: The functional divergence of duplicate genes (ohnologues) retained from whole genome duplication (WGD) is thought to promote evolutionary diversification. However, species radiation and phenotypic diversification are often temporally separated from WGD. Salmonid fish, whose ancestor underwent WGD by autotetraploidization similar to 95 million years ago, fit such a 'time-lag' model of post-WGD radiation, which occurred alongside a major delay in the rediploidization process. Here we propose a model, 'lineage-specific ohnologue resolution' (LORe), to address the consequences of delayed rediploidization. Under LORe, speciation precedes rediploidization, allowing independent ohnologue divergence in sister lineages sharing an ancestral WGD event. Results: Using cross-species sequence capture, phylogenomics and genome-wide analyses of ohnologue expression divergence, we demonstrate the major impact of LORe on salmonid evolution. One-quarter of each salmonid genome, harbouring at least 4550 ohnologues, has evolved under LORe, with rediploidization and functional divergence occurring on multiple independent occasions >50 million years post-WGD. We demonstrate the existence and regulatory divergence of many LORe ohnologues with functions in lineage-specific physiological adaptations that potentially facilitated salmonid species radiation. We show that LORe ohnologues are enriched for different functions than 'older' ohnologues that began diverging in the salmonid ancestor. Conclusions: LORe has unappreciated significance as a nested component of post-WGD divergence that impacts the functional properties of genes, whilst providing ohnologues available solely for lineage-specific adaptation. Under LORe, which is predicted following many WGD events, the functional outcomes of WGD need not appear 'explosively', but can arise gradually over tens of millions of years, promoting lineage-specific diversification regimes under prevailing ecological pressures.

  • 149. Roe, Amanda D.
    et al.
    MacQuarrie, Chris J. K.
    Gros-Louis, Marie-Claude
    Simpson, J. Dale
    Lamarche, Josyanne
    Beardmore, Tannis
    Thompson, Stacey L.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Tanguay, Philippe
    Isabel, Nathalie
    Fitness dynamics within a poplar hybrid zone: I. Prezygotic and postzygotic barriers impacting a native poplar hybrid stand2014In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 4, no 9, p. 1629-1647Article in journal (Refereed)
    Abstract [en]

    Hybridization and introgression are pervasive evolutionary phenomena that provide insight into the selective forces that maintain species boundaries, permit gene flow, and control the direction of evolutionary change. Poplar trees (Populus L.) are well known for their ability to form viable hybrids and maintain their distinct species boundaries despite this interspecific gene flow. We sought to quantify the hybridization dynamics and postzygotic fitness within a hybrid stand of balsam poplar (Populus balsamifera L.), eastern cottonwood (P.deltoides Marsh.), and their natural hybrids to gain insight into the barriers maintaining this stable hybrid zone. We observed asymmetrical hybrid formation with P.deltoides acting as the seed parent, but with subsequent introgression biased toward P.balsamifera. Native hybrids expressed fitness traits intermediate to the parental species and were not universally unfit. That said, native hybrid seedlings were absent from the seedling population, which may indicate additional selective pressures controlling their recruitment. It is imperative that we understand the selective forces maintaining this native hybrid zone in order to quantify the impact of exotic poplar hybrids on this native system.

  • 150. Roe, Amanda D.
    et al.
    MacQuarrie, Chris J. K.
    Gros-Louis, Marie-Claude
    Simpson, J. Dale
    Lamarche, Josyanne
    Beardmore, Tannis
    Thompson, Stacey L.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Tanguay, Philippe
    Isabel, Nathalie
    Fitness dynamics within a poplar hybrid zone: II. Impact of exotic sex on native poplars in an urban jungle2014In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 4, no 10, p. 1876-1889Article in journal (Refereed)
    Abstract [en]

    Trees bearing novel or exotic gene components are poised to contribute to the bioeconomy for a variety of purposes such as bioenergy production, phytoremediation, and carbon sequestration within the forestry sector, but sustainable release of trees with novel traits in large-scale plantations requires the quantification of risks posed to native tree populations. Over the last century, exotic hybrid poplars produced through artificial crosses were planted throughout eastern Canada as ornamentals or windbreaks and these exotics provide a proxy by which to examine the fitness of exotic poplar traits within the natural environment to assess risk of exotic gene escape, establishment, and spread into native gene pools. We assessed postzygotic fitness traits of native and exotic poplars within a naturally regenerated stand in eastern Canada (Quebec City, QC). Pure natives (P.balsamifera and P.deltoides spp. deltoides), native hybrids (P.deltoidesxP.balsamifera), and exotic hybrids (trees bearing Populus nigra and P.maximowiczii genetic components) were screened for reproductive biomass, yield, seed germination, and fungal disease susceptibility. Exotic hybrids expressed fitness traits intermediate to pure species and were not significantly different from native hybrids. They formed fully viable seed and backcrossed predominantly with P.balsamifera. These data show that exotic hybrids were not unfit and were capable of establishing and competing within the native stand. Future research will seek to examine the impact of exotic gene regions on associated biotic communities to fully quantify the risk exotic poplars pose to native poplar forests.

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