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  • 1101.
    Wang, Mi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Uebbing, Severin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Allele-specific gene expression inferred by a Bayesian negative binomial approach indicates abundant cis-regulatory variation in natural flycatcher populationsManuscript (preprint) (Other academic)
    Abstract [en]

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

  • 1102.
    Wang, Wei-Zhou
    et al.
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China; Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Guo, Xiong
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Duan, Chen
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Ma, Wei Juan
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Y G
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Xu, P
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Gao, Z Q
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Wang, Z F
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Yan, H
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Zhang, Y F
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Yu, Y X
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Chen, J C
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Comparative analysis of gene expression profiles between the normal human cartilage and the one with endemic osteoarthritis.2009In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 17, no 1, p. 83-90, article id 18579416Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 1103.
    Wang, Z. Q.
    et al.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria; nternational Agency for Research on Cancer (IARC), F-69008 Lyon, France.
    Stingl, L.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
    Morrison, C.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
    Jantsch, M.
    Department of Cytology and Genetics, University of Vienna, A-1030 Vienna, Austria.
    Los, Marek Jan
    Department of Molecular Oncology/ Pediatry, German Cancer Research Center, D-69120 Heidelberg, Germany.
    Schulze-Osthoff, Klaus
    Medical Clinics, University of Tübingen, D-72076 Tübingen, Germany.
    Wagner, E. F.
    Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
    PARP is important for genomic stability but dispensable in apoptosis1997In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 11, no 18, p. 2347-2358Article in journal (Refereed)
    Abstract [en]

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

  • 1104. Wanschers, Bas F. J.
    et al.
    Szklarczyk, Radek
    van den Brand, Mariel A. M.
    Jonckheere, An
    Suijskens, Janneke
    Smeets, Roel
    Rodenburg, Richard J.
    Stephan, Katharina
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Helland, Ingrid B.
    Elkamil, Areej
    Rootwelt, Terje
    Ott, Martin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    van den Heuvel, Lambert
    Nijtmans, Leo G.
    Huynen, Martijn A.
    A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability2014In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 23, p. 6356-6365Article in journal (Refereed)
    Abstract [en]

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

  • 1105.
    Warnefors, Maria
    et al.
    Heidelberg University of ZMBH, Germany.
    Mossinger, Katharina
    Heidelberg University of ZMBH, Germany.
    Halbert, Jean
    University of Lausanne, Switzerland.
    Studer, Tania
    Heidelberg University of ZMBH, Germany.
    VandeBerg, John L.
    University of Texas Rio Grande Valley, TX 78520 USA.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Fallahshahroudi, Amir
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Kaessmann, Henrik
    Heidelberg University of ZMBH, Germany.
    Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation2017In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 27, no 12, p. 1961-1973Article in journal (Refereed)
    Abstract [en]

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

  • 1106. Wayne, R.K
    et al.
    Geffen, E.
    Vilà, C.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Conservation Genetics of Canids2004In: Canids: Foxes, Wolves, Jackals and Dogs.: Status Survey and Conservation Aciton Plan, IUCN/SSC Canid Specialist Group, Gland, Switzerland. Cambridge, UK. , 2004Chapter in book (Other scientific)
  • 1107. Wayne, R.K.
    et al.
    Geffen, E.
    Vilà, C.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Population and conservation genetics of canids.2004In: Biology and Conservation of Wild Canids., Oxford University Press , 2004Chapter in book (Other scientific)
  • 1108.
    Weber, Claudia C.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Boussau, Bastien
    Romiguier, Jonathan
    Jarvis, Erich D.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Evidence for GC-biased gene conversion as a driver of between-lineage differences in avian base composition2014In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 15, no 12, p. 549-Article in journal (Refereed)
    Abstract [en]

    Background While effective population size (N-e) and life history traits such as generation time are known to impact substitution rates, their potential effects on base composition evolution are less well understood. GC content increases with decreasing body mass in mammals, consistent with recombination-associated GC biased gene conversion (gBGC) more strongly impacting these lineages. However, shifts in chromosomal architecture and recombination landscapes between species may complicate the interpretation of these results. In birds, interchromosomal rearrangements are rare and the recombination landscape is conserved, suggesting that this group is well suited to assess the impact of life history on base composition. Results Employing data from 45 newly and 3 previously sequenced avian genomes covering a broad range of taxa, we found that lineages with large populations and short generations exhibit higher GC content. The effect extends to both coding and non-coding sites, indicating that it is not due to selection on codon usage. Consistent with recombination driving base composition, GC content and heterogeneity were positively correlated with the rate of recombination. Moreover, we observed ongoing increases in GC in the majority of lineages. Conclusions Our results provide evidence that gBGC may drive patterns of nucleotide composition in avian genomes and are consistent with more effective gBGC in large populations and a greater number of meioses per unit time; that is, a shorter generation time. Thus, in accord with theoretical predictions, base composition evolution is substantially modulated by species life history.

  • 1109.
    Weber, Claudia C.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nabholz, Benoit
    Romiguier, Jonathan
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    K-r/K-c but not d(N)/d(S) correlates positively with body mass in birds, raising implications for inferring lineage-specific selection2014In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 15, no 12, p. 542-Article in journal (Refereed)
    Abstract [en]

    Background: The ratio of the rates of non-synonymous and synonymous substitution (d(N)/d(S)) is commonly used to estimate selection in coding sequences. It is often suggested that, all else being equal, d(N)/d(S) should be lower in populations with large effective size (Ne) due to increased efficacy of purifying selection. As N-e is difficult to measure directly, life history traits such as body mass, which is typically negatively associated with population size, have commonly been used as proxies in empirical tests of this hypothesis. However, evidence of whether the expected positive correlation between body mass and d(N)/d(S) is consistently observed is conflicting. Results: Employing whole genome sequence data from 48 avian species, we assess the relationship between rates of molecular evolution and life history in birds. We find a negative correlation between dN/dS and body mass, contrary to nearly neutral expectation. This raises the question whether the correlation might be a method artefact. We therefore in turn consider non-stationary base composition, divergence time and saturation as possible explanations, but find no clear patterns. However, in striking contrast to d(N)/d(S), the ratio of radical to conservative amino acid substitutions (K-r/K-c) correlates positively with body mass. Conclusions: Our results in principle accord with the notion that non-synonymous substitutions causing radical amino acid changes are more efficiently removed by selection in large populations, consistent with nearly neutral theory. These findings have implications for the use of d(N)/d(S) and suggest that caution is warranted when drawing conclusions about lineage-specific modes of protein evolution using this metric.

  • 1110.
    Webster, Matthew T
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Smith, Nick G C
    Hultin-Rosenberg, Lina
    Arndt, Peter F
    Ellegren, Hans
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Male-driven biased gene conversion governs the evolution of base composition in human alu repeats.2005In: Mol Biol Evol, ISSN 0737-4038, Vol. 22, no 6, p. 1468-74Article in journal (Refereed)
    Abstract [en]

    Regional biases in substitution pattern are likely to be responsible for the large-scale variation in base composition observed in vertebrate genomes. However, the evolutionary forces responsible for these biases are still not clearly defined. In order to study the processes of mutation and fixation across the entire human genome, we analyzed patterns of substitution in Alu repeats since their insertion. We also studied patterns of human polymorphism within the repeats. There is a highly significant effect of recombination rate on the pattern of substitution, whereas no such effect is seen on the pattern of polymorphism. These results suggest that regional biases in substitution are caused by biased gene conversion, a process that increases the probability of fixation of mutations that increase GC content. Furthermore, the strongest correlate of substitution patterns is found to be male recombination rates rather than female or sex-averaged recombination rates. This indicates that in addition to sexual dimorphism in recombination rates, the sexes also differ in the relative rates of crossover and gene conversion.

  • 1111.
    Webster, Matthew T.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Smith, Nick G.C.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Lercher, M.J.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Gene expression, synteny, and local similarity in human noncoding mutation rates2004In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 21, no 10, p. 1820-1830Article in journal (Refereed)
    Abstract [en]

    The human genome is organized with regard to many features such as isochores, Giemsa bands, clusters of genes with similar expression patterns, and contiguous regions with shared evolutionary histories (synteny blocks). In addition to these genomic features, it is clear that mutation rates also vary across the human genome. To address how mutation rates and genomic features are related, we analyzed substitution rates at three classes of putatively neutral noncoding sites (nongenic, intronic, and ancestral repeats) in approximately 14 Mb of human-chimpanzee alignments covering human chromosome 7. Patterns of mutation rate variation inferred from substitution rate variation differ among the three site classes. In particular, we find that intronic mutation rates are strongly affected by the breadth of expression of the genes in which they reside, with broadly expressed genes exhibiting low mutation rates, probably as a consequence of the transcription-coupled repair process acting in the germ line. All site classes show significant local similarities in mutation rate at the megabase scale, and regional similarities in nongenic mutation rate covary with blocks of synteny between the human and mouse genomes, indicating that the evolutionary history of a genomic region is an important determinant of mutation rate.

  • 1112.
    Webster, Matthew Thomas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Smith, Nick G.C.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Evolutionary Biology.
    Fixation biases affecting human SNPs?2004In: Trends in Genetics, ISSN 0168-9525, E-ISSN 1362-4555, Vol. 20, no 3, p. 122-126Article in journal (Refereed)
    Abstract [en]

    Under neutrality all classes of mutation have an equal probability of becoming fixed in a population. In this article, we describe our analysis of the frequency distributions of >5000 human SNPs and provide evident of biases in the process of fixation of certain classes of point mutation that are most likely to be attributable to biased gene conversion. The results indicate an increased fixation probability of mutations that result in the incorporation of a GC base pair. Furthermore, in transcribed regions this process exhibits strand asymmetry, and is biased towards preserving a G base on the coding strand. Biased gene conversion has the potential to explain both existence of isochores and the compositional asymmetry in mammalian transcribed regions.

  • 1113. Wedin, Mats
    et al.
    Wiklund, Elisabeth
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Jorgensen, Per Magnus
    Ekman, Stefan
    Slippery when wet: phylogeny and character evolution in the gelatinous cyanobacterial lichens (Peltigerales, Ascomycetes)2009In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 53, no 3, p. 862-871Article in journal (Refereed)
    Abstract [en]

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

  • 1114.
    Wei, Yu-Dan
    Stockholm University.
    Tryptophan photoproducts: regulation of CYP1A1 transcription and modulation of cell growth2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in the regulation of many drug-metabolizing enzymes. The regulation of cytochrome P4501A1 (CYP1A1) has been most intensively studied. A large number of highly toxic environmental compounds, such as dioxins and PAHs are ligands for the AhR and give rise to CYP1A1 induction. Also, UV-light induces CYP1A1. Accumulating data indicate the existence of endogenous ligands for the AhR which, however, remain to be identified. UV-irradiation of the amino acid tryptophan produces photoproducts that possess very high binding affinities for the AhR. These photoproducts have therefore been suggested as possible endogenous ligands for the AhR. The biologically most active compound has been identified as 6-formylindolo[3,2-b]carbazole (FICZ).

    The aim of the present study was to further investigate these compounds, focusing on FICZ , with respect to the regulation of CYP1A1 transcription and the modulation of cell growth, as well as their possible formation in biological systems. The study was carried out using different cultured mammalian cells, including two types of human cells (a keratinocyte cell line and peripheral blood mononuclear cells) as well as mouse hepatoma Hepa-1 cell lines.

    Experiments with dose- and time-dependent induction and comparison with other inducers showed that FICZ is a potent inducer of CYP1A1 mRNA and that the induction appears very rapidly and is transient in nature. Metabolism studies using Aroclor-induced rat liver S9 and S9 from mouse Hepa-1 cells with HPLC analysis revealed that the transient induction of CYP1A1 mRNA by FICZ was due to its metabolism by the CYP1A1 enzyme. These results, together with gene expression studies, indicated that the level of CYP1A1 mRNA induced by FICZ is auto-negatively controlled by the induced CYP1A1 enzyme and that FICZ thus behaves as an endogenous substrate involved in the autoregulation mechanism. Additionally, the studies in human cells showed that tryptophan facilitates UV-induced CYP1A1 gene expression, indicating that the tryptophan photoproducts may be formed in the cells upon UV-irradiation.

    The role of CYP1A1 in the regulation of cell growth was characterized. Observations of a slower cell proliferation in wild-type Hepa-1 cells compared to cells lacking CYP1A1 activity indicated that CYP1A1 could reduce cell growth most likely by metabolizing an endogenous substrate that stimulates growth. The results were confirmed by restoring the CYP1A1 activity in the deficient cells by transfection. FICZ was shown to enhance cell proliferation and modulate the expression of genes involved in signal transduction.

    In conclusion, the results provide evidence for tryptophan-derived substances as being endogenous AhR ligands which autoregulate CYP1A1 transcription and activate cell growth. These findings will form a basis for a better understanding of the physiological processes that are regulated by the AhR and CYP1A1 and thereby also a better understanding of the mechanisms by which xenobiotics disrupt these processes.

  • 1115.
    Weishaupt, Holger
    et al.
    Mälardalen University, School of Education, Culture and Communication, Educational Sciences and Mathematics. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.
    Johansson, Patrik
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.
    Engström, Christopher
    Mälardalen University, School of Education, Culture and Communication, Educational Sciences and Mathematics.
    Nelander, Sven
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.
    Silvestrov, Sergei
    Mälardalen University, School of Education, Culture and Communication, Educational Sciences and Mathematics.
    Swartling, Fredrik
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.
    Graph Centrality Based Prediction of Cancer Genes2016In: Engineering Mathematics II: Algebraic, Stochastic and Analysis Structures for Networks, Data Classification and Optimization / [ed] Sergei Silvestrov; Milica Rancic, Springer, 2016, p. 275-311Chapter in book (Refereed)
    Abstract [en]

    Current cancer therapies including surgery, radiotherapy and chemotherapy are often plagued by high failure rates. Designing more targeted and personalized treatment strategies requires a detailed understanding of druggable tumor drivergenes. As a consequence, the detection of cancer driver genes has evolved to a critical scientific field integrating both high-through put experimental screens as well as computational and statistical strategies. Among such approaches, network based prediction tools have recently been accentuated and received major focus due to their potential to model various aspects of the role of cancer genes in a biological system. In this chapter, we focus on how graph centralities obtained from biological networks have been used to predict cancer genes. Specifically, we start by discussing the current problems in cancer therapy and the reasoning behind using network based cancer gene prediction, followed by an outline of biological networks, their generation and properties. Finally, we review major concepts, recent results as well as future challenges regarding the use of graph centralities in cancer gene prediction.

  • 1116. Weiste, Christoph
    et al.
    Pedrotti, Lorenzo
    Selvanayagam, Jebasingh
    Muralidhara, Prathibha
    Fröschel, Christian
    Novák, Ondřej
    Ljung, Karin
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Dröge-Laser, Wolfgang
    The Arabidopsis bZIP11 transcription factor links low-energy signalling to auxin-mediated control of primary root growth2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 2Article in journal (Refereed)
    Abstract [en]

    Plants have to tightly control their energy homeostasis to ensure survival and fitness under constantly changing environmental conditions. Thus, it is stringently required that energy-consuming stress-adaptation and growth-related processes are dynamically tuned according to the prevailing energy availability. The evolutionary conserved SUCROSE NON-FERMENTING1 RELATED KINASES1 (SnRK1) and the downstream group C/S1 basic leucine zipper (bZIP) transcription factors (TFs) are well-characterised central players in plants' low-energy management. Nevertheless, mechanistic insights into plant growth control under energy deprived conditions remains largely elusive. In this work, we disclose the novel function of the low-energy activated group S1 bZIP11-related TFs as regulators of auxin-mediated primary root growth. Whereas transgenic gain-of-function approaches of these bZIPs interfere with the activity of the root apical meristem and result in root growth repression, root growth of loss-of-function plants show a pronounced insensitivity to low-energy conditions. Based on ensuing molecular and biochemical analyses, we propose a mechanistic model, in which bZIP11-related TFs gain control over the root meristem by directly activating IAA3/SHY2 transcription. IAA3/SHY2 is a pivotal negative regulator of root growth, which has been demonstrated to efficiently repress transcription of major auxin transport facilitators of the PIN-FORMED (PIN) gene family, thereby restricting polar auxin transport to the root tip and in consequence auxin-driven primary root growth. Taken together, our results disclose the central low-energy activated SnRK1-C/S1-bZIP signalling module as gateway to integrate information on the plant's energy status into root meristem control, thereby balancing plant growth and cellular energy resources.

  • 1117. Welderufael, Berihu
    et al.
    De Koning, Dirk-Jan
    Fikse, Freddy
    Strandberg, Erling
    Franzén, Jessica
    Stockholm University, Faculty of Social Sciences, Department of Statistics.
    Christensen, O. F.
    Genetic Evaluation of Mastistis Liability and Recovery through Longitudinal Models of SCC2013Conference paper (Refereed)
  • 1118. Welderufael, Berihu
    et al.
    Fikse, Freddy
    Franzén, Jessica
    Stockholm University, Faculty of Social Sciences, Department of Statistics.
    Strandberg, Erling
    Christensen, O. F.
    De Koning, Dirk-Jan
    Genetic Evaluation of Getting and Recovering from an Intramammary Infection through Longitudinal Models of Somatic Cell Count2013Conference paper (Refereed)
  • 1119. Wellenreuther, M.
    et al.
    Rosenquist, H.
    Jaksons, P.
    Larson, Keith W
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Local adaptation along an environmental cline in a species with an inversion polymorphism2017In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 30, no 6, p. 1068-1077Article in journal (Refereed)
    Abstract [en]

    Polymorphic inversions are ubiquitous across the animal kingdom and are frequently associated with clines in inversion frequencies across environmental gradients. Such clines are thought to result from selection favouring local adaptation; however, empirical tests are scarce. The seaweed fly Coelopa frigida has an alpha/beta inversion polymorphism, and previous work demonstrated that the alpha inversion frequency declines from the North Sea to the Baltic Sea and is correlated with changes in tidal range, salinity, algal composition and wrackbed stability. Here, we explicitly test the hypothesis that populations of C. frigida along this cline are locally adapted by conducting a reciprocal transplant experiment of four populations along this cline to quantify survival. We found that survival varied significantly across treatments and detected a significant Location x Substrate interaction, indicating local adaptation. Survival models showed that flies from locations at both extremes had highest survival on their native substrates, demonstrating that local adaptation is present at the extremes of the cline. Survival at the two intermediate locations was, however, not elevated at the native substrates, suggesting that gene flow in intermediate habitats may override selection. Together, our results support the notion that population extremes of species with polymorphic inversions are often locally adapted, even when spatially close, consistent with the growing view that inversions can have direct and strong effects on the fitness of species.

  • 1120. Wennerstrom, Lovisa
    et al.
    Ryman, Nils
    Tison, Jean-Luc
    Hasslow, Anna
    Dalén, Love
    Swedish Museum of Natural History, Department of Bioinformatics and Genetics.
    Laikre, Linda
    Genetic landscape with sharp discontinuities shaped by complex demographic history in moose (Alces alces)2016In: Journal of Mammalogy, ISSN 0022-2372, E-ISSN 1545-1542, Vol. 97, no 1, p. 1-13Article in journal (Refereed)
    Abstract [en]

    The moose (Alces alces) is the most intensely managed game species in Fennoscandia; approximately one-third of the population, ca. 160,000 animals, is harvested annually. Despite the species' biological and socioeconomic importance, there are knowledge gaps with respect to its intraspecific diversity and genetic structure. Recent studies of moose in neighboring countries report 2 genetic groups in Finland, 3 in Norway with one of them suggested to be of ancient origin, and no indications of bottlenecks. To delineate the spatial genetic landscape of the Swedish moose, we used allozyme variability from over 20,000 georeferenced moose collected all over Sweden in combination with 12 microsatellites (n = 1,200) and mitochondrial DNA (mtDNA) sequences (n = 44). We combined individual-based and traditional statistical approaches with coalescence-based simulations. The results indicate a complex history with bottlenecks and recent expansions that is consistent with historical records. Swedish moose are separated into 2 major genetic groups, a northern and a southern one, where the southern group is further divided into 3 subgroups. The 2 main subpopulations are moderately differentiated (F-ST = 0.1; R-ST = 0.07) and separated by sharp genetic discontinuities occurring over a relatively narrow transition zone in central Sweden that coincides with a similar, previously reported transition zone in Norway. This differentiation is not reflected in mtDNA variation, where no significant divergence was observed. Together with the F-ST andR(ST) similarities, this suggests that the 2 major subpopulations in Sweden reflect divergence shaped after the postglacial recolonization of Scandinavia. Neighborhood size assessments indicate that gene flow is relatively restricted with an estimated average dispersal distance of 3.5-11.1 km, and spatial autocorrelograms suggest that genetic similarity decreases almost linearly over space resulting in continuous genetic clines within major subgroups. Management areas largely coincide with genetic clusters, simplifying the integration of genetic information into management.

  • 1121. Westin, M A K
    et al.
    Hunt, M C
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. Genetik.
    Alexson, S E H
    Short- and medium-chain carnitine acyltransferases and acyl-CoA thioesterases in mouse provide complementary systems for transport of beta-oxidation products out of peroxisomes.2008In: Cell Mol Life Sci, ISSN 1420-682X, Vol. 65, no 6, p. 982-90Article in journal (Refereed)
  • 1122.
    Westman, Anna-Karin
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Natural Sciences, Engineering and Mathematics.
    Investigation of Progress in Peer Discussions Regarding Genetic ConceptsManuscript (preprint) (Other academic)
  • 1123.
    Wetterbom, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sevov, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Cavelier, Lucia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Bergström, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Comparative genomic analysis of human and chimpanzee indicates a key role for indels in primate evolution2006In: Journal of Molecular Evolution, ISSN 0022-2844, E-ISSN 1432-1432, Vol. 63, no 5, p. 682-690Article in journal (Refereed)
    Abstract [en]

    Sequence comparison of humans and chimpanzees is of interest to understand the mechanisms behind primate evolution. Here we present an independent analysis of human chromosome 21 and the high-quality BAC clone sequences of the homologous chimpanzee chromosome 22. In contrast to previous studies, we have used global alignment methods and Ensembl predictions of protein coding genes (n = 224) for the analysis. Divergence due to insertions and deletions (indels) along with substitutions was examined separately for different genomic features (coding, noncoding genic, and intergenic sequence). The major part of the genomic divergence could be attributed to indels (5.07%), while the nucleotide divergence was estimated as 1.52%. Thus the total divergence was estimated as 6.58%. When excluding repeats and low-complexity DNA the total divergence decreased to 2.37%. The chromosomal distribution of nucleotide substitutions and indel events was significantly correlated. To further examine the role of indels in primate evolution we focused on coding sequences. Indels were found within the coding sequence of 13% of the genes and approximately half of the indels have not been reported previously. In 5% of the chimpanzee genes, indels or substitutions caused premature stop codons that rendered the affected transcripts nonfunctional. Taken together, our findings demonstrate that indels comprise the majority of the genomic divergence. Furthermore, indels occur frequently in coding sequences. Our results thereby support the hypothesis that indels may have a key role in primate evolution.

  • 1124.
    Wheatcroft, David
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Genetic divergence of early song discrimination between two young songbird species2017In: NATURE ECOLOGY & EVOLUTION, ISSN 2397-334X, Vol. 1, no 7, article id UNSP 0192Article in journal (Refereed)
    Abstract [en]

    Juvenile songbirds express species-specific song discrimination from an early age, which focuses learning onto the songs of their parental species. However, it remains unknown whether this early song discrimination is influenced by early social experience or maternal effects or whether it is instead largely genetically determined. We manipulated early social experience by swapping young embryos between the nests of two co-occurring songbird species-pied and collared flycatchers. We show that nestlings are more active in response to playbacks of conspecific songs, even when raised by adults from the other species, thus enabling us to reject social experience as the main determinant of early song discrimination. We then crossed the two species in captivity and showed that the song responses of hybrid nestlings do not depend on social experience or maternal species, implying genetic divergence of early song discrimination. Our results provide conclusive evidence that early song discrimination has a largely genetic component, which can stabilize reproductive isolation by reducing song learning across closely related species.

  • 1125.
    Widell, Paulina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Genetiken bakom artbildning: fokus på Leptidea Sinapis2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Artbildning, det vill säga uppkomst av nya arter, är ett centralt ämne inom evolutionsbiologinoch en process som kan fortskrida på ett flertal olika sätt. Reproduktiva barriärer som är nödvändiga för artbildningsprocessen kan utvecklas mellan populationer och verkar antingen så att individer hindras från att para sig med varandra (prezygotisk isolering) eller så att överlevnad eller reproduktionsframgång hos avkomman är reducerad (postzygotisk isolering).Syftet men där här studien är att först beskriva dessa olika typer av isoleringar och sedan summera den aktuella kunskapen om hur själva artbildningsprocessen kan fortgå. Avslutningvis beskrivs ett exempelsystem med tre geografiskt separerade populationer avarten skogsvitsvinge (Leptidea sinapis). Skillnader i kromosomantal och ekologi mellan vissa av populationerna kan potentiellt vara faktorer som har lett till begränsat genflöde och som i slutänden kan leda till att fullständigt reproduktivt isolerade arter uppkommer.

  • 1126. Willems, Sara M.
    et al.
    Wright, Daniel J.
    Day, Felix R.
    Trajanoska, Katerina
    Joshi, Peter K.
    Morris, John A.
    Matteini, Amy M.
    Garton, Fleur C.
    Grarup, Niels
    Oskolkov, Nikolay
    Thalamuthu, Anbupalam
    Mangino, Massimo
    Liu, Jun
    Demirkan, Ayse
    Lek, Monkol
    Xu, Liwen
    Wang, Guan
    Oldmeadow, Christopher
    Gaulton, Kyle J.
    Lotta, Luca A.
    Miyamoto-Mikami, Eri
    Rivas, Manuel A.
    White, Tom
    Loh, Po-Ru
    Aadahl, Mette
    Amin, Najaf
    Attia, John R.
    Austin, Krista
    Benyamin, Beben
    Brage, Soren
    Cheng, Yu-Ching
    Cieszczyk, Pawel
    Derave, Wim
    Eriksson, Karl-Fredrik
    Eynon, Nir
    Linneberg, Allan
    Lucia, Alejandro
    Massidda, Myosotis
    Mitchell, Braxton D.
    Miyachi, Motohiko
    Murakami, Haruka
    Padmanabhan, Sandosh
    Pandey, Ashutosh
    Papadimitriou, Loannis
    Rajpal, Deepak K.
    Sale, Craig
    Schnurr, Theresia M.
    Sessa, Francesco
    Shrine, Nick
    Tobin, Martin D.
    Varley, Ian
    Wain, Louise V.
    Wray, Naomi R.
    Lindgren, Cecilia M.
    MacArthur, Daniel G.
    Waterworth, Dawn M.
    McCarthy, Mark I.
    Pedersen, Oluf
    Khaw, Kay-Tee
    Kie, Douglas P.
    Pitsiladis, Yannis
    Fuku, Noriyuki
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skånes University Hospital, 222 41 Lund, Sweden.
    North, Kathryn N.
    van Duijn, Cornelia M.
    Mather, Karen A.
    Hansen, Torben
    Hansson, Ola
    Spector, Tim
    Murabito, Joanne M.
    Richards, J. Brent
    Rivadeneira, Fernando
    Langenberg, Claudia
    Perry, John R. B.
    Wareham, Nick J.
    Scott, Robert A.
    Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 16015Article in journal (Refereed)
    Abstract [en]

    Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 x 10(-8)) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

  • 1127. Williams, Jessica S
    et al.
    Clausen, Anders R
    Nick McElhinny, Stephanie A
    Watts, Brian E
    Johansson, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kunkel, Thomas A
    Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase ɛ.2012In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 11, no 8, p. 649-656Article in journal (Refereed)
    Abstract [en]

    We have investigated the ability of the 3' exonuclease activity of Saccharomyces cerevisiae DNA polymerase ɛ (Pol ɛ) to proofread newly inserted ribonucleotides (rNMPs). During DNA synthesis in vitro, Pol ɛ proofreads ribonucleotides with apparent efficiencies that vary from none at some locations to more than 90% at others, with rA and rU being more efficiently proofread than rC and rG. Previous studies show that failure to repair ribonucleotides in the genome of rnh201Δ strains that lack RNase H2 activity elevates the rate of short deletions in tandem repeat sequences. Here we show that this rate is increased by 2-4-fold in pol2-4 rnh201Δ strains that are also defective in Pol ɛ proofreading. In comparison, defective proofreading in these same strains increases the rate of base substitutions by more than 100-fold. Collectively, the results indicate that although proofreading of an 'incorrect' sugar is less efficient than is proofreading of an incorrect base, Pol ɛ does proofread newly inserted rNMPs to enhance genome stability.

  • 1128. Wilsker, Deborah
    et al.
    Chung, Jon H.
    Pradilla, Ivan
    Petermann, Eva
    Helleday, Thomas
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Bunz, Fred
    Targeted Mutations in the ATR Pathway Define Agent-Specific Requirements for Cancer Cell Growth and Survival2012In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 11, no 1, p. 98-107Article in journal (Refereed)
    Abstract [en]

    Many anticancer agents induce DNA strand breaks or cause the accumulation of DNA replication intermediates. The protein encoded by ataxia-telangiectasia mutated and Rad 3-related (ATR) generates signals in response to these altered DNA structures and activates cellular survival responses. Accordingly, ATR has drawn increased attention as a potential target for novel therapeutic strategies designed to potentiate the effects of existing drugs. In this study, we use a unique panel of genetically modified human cancer cells to unambiguously test the roles of upstream and downstream components of the ATR pathway in the responses to common therapeutic agents. Upstream, the S-phase-specific cyclin-dependent kinase (Cdk) 2 was required for robust activation of ATR in response to diverse chemotherapeutic agents. While Cdk2-mediated ATR activation promoted cell survival after treatment with many drugs, signaling from ATR directly to the checkpoint kinase Chk1 was required for survival responses to only a subset of the drugs tested. These results show that specifically inhibiting the Cdk2/ATR/Chk1 pathway via distinct regulators can differentially sensitize cancer cells to a wide range of therapeutic agents.

  • 1129. Wind, Julia J.
    et al.
    Peviani, Alessia
    Snel, Berend
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Smeekens, Sjef C.
    ABI4: versatile activator and repressor2013In: Trends in Plant Science, ISSN 1360-1385, E-ISSN 1878-4372, Vol. 18, no 3, p. 125-132Article in journal (Refereed)
    Abstract [en]

    The ABSCISIC ACID INSENSITIVE4 (ABI4) gene was discovered to be an abscisic acid (ABA) signaling responsive transcription factor active during seed germination. The evolutionary history of the ABI4 gene supports its role as an ABA signaling intermediate in land plants. Investigating the ABI4 protein-cis element interaction supports the proposal that ABI4 binding to its known CE1 cis-element competes with transcription factor binding to the overlapping G-Box element. Recent publications report on ABI4 as a regulatory factor in diverse processes. In developing seedlings, ABI4 mediates sugar signaling, lipid breakdown, and plastid-to-nucleus signaling. Moreover, ABI4 is a regulator of rosette growth, redox signaling, cell wall metabolism and the effect of nitrate on lateral root development.

  • 1130.
    Wittenburg, Dörte
    et al.
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Melzer, Nina
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Willmitzer, Lothar
    Max Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Lisec, Jan
    Max Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Kesting, U
    Landeskontrollverband für Leistungs, Qualitätsprüfung Mecklenburg-Vorpommern e.V. (LKV), Güstrow, Germany .
    Reinsch, Norbert
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Repsilber, Dirk
    Institute for Genetics and Biometry, Unit Biomathematics and Bioinformatics, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany .
    Milk metabolites and their genetic variability2013In: Journal of Dairy Science, ISSN 0022-0302, E-ISSN 1525-3198, Vol. 96, no 4, p. 2557-69Article in journal (Refereed)
    Abstract [en]

    The composition of milk is crucial to evaluate milk performance and quality measures. Milk components partly contribute to breeding scores, and they can be assessed to judge metabolic and energy status of the cow as well as to serve as predictive markers for diseases. In addition to the milk composition measures (e.g., fat, protein, lactose) traditionally recorded during milk performance test via infrared spectroscopy, novel techniques, such as gas chromatography-mass spectrometry, allow for a further analysis of milk into its metabolic components. Gas chromatography-mass spectrometry is suitable for measuring several hundred metabolites with high throughput, and thus it is applicable to study sources of genetic and nongenetic variation of milk metabolites in dairy cows. Heritability and mode of inheritance of metabolite measurements were studied in a linear mixed model approach including expected (pedigree) and realized (genomic) relationship between animals. The genetic variability of 190 milk metabolite intensities was analyzed from 1,295 cows held on 18 farms in Mecklenburg-Western Pomerania, Germany. Besides extensive pedigree information, genotypic data comprising 37,180 single nucleotide polymorphism markers were available. Goodness of fit and significance of genetic variance components based on likelihood ratio tests were investigated with a full model, including marker- and pedigree-based genetic effects. Broad-sense heritability varied from zero to 0.699, with a median of 0.125. Significant additive genetic variance was observed for highly heritable metabolites, but dominance variance was not significantly present. As some metabolites are particularly favorable for human nutrition, for instance, future research should address the identification of locus-specific genetic effects and investigate metabolites as the molecular basis of traditional milk performance test traits.

  • 1131.
    Wolf, Jochen B. W.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Ludwig Maximilian Univ Munich, Dept Biol 2, Sect Evolutionary Biol, Grosshaderner Str 2, D-82152 Planegg Martinsried, Germany..
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Making sense of genomic islands of differentiation in light of speciation2017In: Nature reviews genetics, ISSN 1471-0056, E-ISSN 1471-0064, Vol. 18, no 2, p. 87-100Article, review/survey (Refereed)
    Abstract [en]

    As populations diverge, genetic differences accumulate across the genome. Spurred by rapid developments in sequencing technology, genome-wide population surveys of natural populations promise insights into the evolutionary processes and the genetic basis underlying speciation. Although genomic regions of elevated differentiation are the focus of searches for 'speciation genes', there is an increasing realization that such genomic signatures can also arise by alternative processes that are not related to population divergence, such as linked selection. In this Review, we explore methodological trends in speciation genomic studies, highlight the difficulty in separating processes related to speciation from those emerging from genome-wide properties that are not related to reproductive isolation, and provide a set of suggestions for future work in this area.

  • 1132. Wong, Gane Ka-Shu
    et al.
    Liu, Bin
    Wang, Jun
    Zhang, Yong
    Yang, Xu
    Zhang, Zengjin
    Meng, Qingshun
    Zhou, Jun
    Li, Dawei
    Zhang, Jingjing
    Ni, Peixiang
    Li, Songgang
    Ran, Longhua
    Li, Heng
    Zhang, Jianguo
    Li, Ruiqiang
    Li, Shengting
    Zheng, Hongkun
    Lin, Wei
    Li, Guangyuan
    Wang, Xiaoling
    Zhao, Wenming
    Li, Jun
    Ye, Chen
    Dai, Mingtao
    Ruan, Jue
    Zhou, Yan
    Li, Yuanzhe
    He, Ximiao
    Zhang, Yunze
    Wang, Jing
    Huang, Xiangang
    Tong, Wei
    Chen, Jie
    Ye, Jia
    Chen, Chen
    Wei, Ning
    Li, Guoqing
    Dong, Le
    Lan, Fengdi
    Sun, Yongqiao
    Zhang, Zhenpeng
    Yang, Zheng
    Yu, Yingpu
    Huang, Yanqing
    He, Dandan
    Xi, Yan
    Wei, Dong
    Qi, Qiuhui
    Li, Wenjie
    Shi, Jianping
    Wang, Miaoheng
    Xie, Fei
    Wang, Jianjun
    Zhang, Xiaowei
    Wang, Pei
    Zhao, Yiqiang
    Li, Ning
    Yang, Ning
    Dong, Wei
    Hu, Songnian
    Zeng, Changqing
    Zheng, Weimou
    Hao, Bailin
    Hillier, Ladeana W
    Yang, Shiaw-Pyng
    Warren, Wesley C
    Wilson, Richard K
    Brandström, Mikael
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Ellegren, Hans
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Crooijmans, Richard P M A
    van der Poel, Jan J
    Bovenhuis, Henk
    Groenen, Martien A M
    Ovcharenko, Ivan
    Gordon, Laurie
    Stubbs, Lisa
    Lucas, Susan
    Glavina, Tijana
    Aerts, Andrea
    Kaiser, Pete
    Rothwell, Lisa
    Young, John R
    Rogers, Sally
    Walker, Brian A
    van Hateren, Andy
    Kaufman, Jim
    Bumstead, Nat
    Lamont, Susan J
    Zhou, Huaijun
    Hocking, Paul M
    Morrice, David
    de Koning, Dirk-Jan
    Law, Andy
    Bartley, Neil
    Burt, David W
    Hunt, Henry
    Cheng, Hans H
    Gunnarsson, Ulrika
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Wahlberg, Per
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Andersson, Leif
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Kindlund, Ellen
    Tammi, Martti T
    Andersson, Björn
    Webber, Caleb
    Ponting, Chris P
    Overton, Ian M
    Boardman, Paul E
    Tang, Haizhou
    Hubbard, Simon J
    Wilson, Stuart A
    Yu, Jun
    Wang, Jian
    Yang, Huanming
    A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms.2004In: Nature, ISSN 1476-4687, Vol. 432, no 7018, p. 717-22Article in journal (Refereed)
  • 1133.
    Woronik, Alyssa
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Neethiraj, Ramprasad
    Stockholm University, Faculty of Science, Department of Zoology.
    Lehmann, Philipp
    Stockholm University, Faculty of Science, Department of Zoology.
    Maria, de la Paz Celorio Mancera
    Stockholm University, Faculty of Science, Department of Zoology.
    Stefanescu, Constanti
    Hill, Jason
    Stockholm University, Faculty of Science, Department of Zoology.
    Käkelä, Reijo
    Brattstrom, Oskar
    Wheat, Christopher
    Stockholm University, Faculty of Science, Department of Zoology.
    A transposable element insertion is associated with a female-limited, alternative life history strategyManuscript (preprint) (Other academic)
  • 1134. Wrzaczek, Michael
    et al.
    Vainonen, Julia P.
    Stael, Simon
    Tsiatsiani, Liana
    Help-Rinta-Rahko, Hanna
    Gauthier, Adrien
    Kaufholdt, David
    Bollhöner, Benjamin
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lamminmaki, Airi
    Staes, An
    Gevaert, Kris
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Van Breusegem, Frank
    Helariutta, Yka
    Kangasjarvi, Jaakko
    GRIM REAPER peptide binds to receptor kinase PRK5 to trigger cell death in Arabidopsis2015In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 31, no 1, p. 55-66Article in journal (Refereed)
    Abstract [en]

    Recognition of extracellular peptides by plasma membrane-localized receptor proteins is commonly used in signal transduction. In plants, very little is known about how extracellular peptides are processed and activated in order to allow recognition by receptors. Here, we show that induction of cell death in planta by a secreted plant protein GRIM REAPER (GRI) is dependent on the activity of the type II metacaspase METACASPASE-9. GRI is cleaved by METACASPASE-9 in vitro resulting in the release of an 11 amino acid peptide. This peptide bound in vivo to the extracellular domain of the plasma membrane-localized, atypical leucine-rich repeat receptor-like kinase POLLEN-SPECIFIC RECEPTOR-LIKE KINASE 5 (PRK5) and was sufficient to induce oxidative stress/ROS-dependent cell death. This shows a signaling pathway in plants from processing and activation of an extracellular protein to recognition by its receptor.

  • 1135. Wu, Chenglin
    et al.
    Mignardi, Marco
    chen, lei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landegren, Ulf
    Nilsson, Mats
    Profiling and genotyping individual mRNA molecules through in situ sequencing of super rolling circle amplification productsManuscript (preprint) (Other academic)
    Abstract [en]

    We have recently developed a technology for localized sequence library preparation with rolling-circle amplification (RCA) as an approach for in situ sequencing. This method involves generation of clonally amplified and specially confined substrates for next-generation sequencing within the preserved context of cells and tissues. Our approach combines padlock probing, RCA, and sequencing-by-ligation chemistry that can resolve expression profiles of sets of genes and mutations in tissues without loss of histological context. Like other fluorescence-based assays, it can be hindered by high level of background fluorescence. To achieve high signal-to-noise ratios, we now describe a method to boost the amplification generated by RCA of padlock probes in situ by super RCA (sRCA). In this technique, a second padlock probe is hybridized, ligated and amplified on the first RCA product for enhanced, localized amplification. We describe and compare different sRCA strategies where gap-fill ligation was showed to be most efficient. The sRCA products co-localize and have comparable sizes as RCA products but they display at least two fold higher signal intensity. This increase in signal to noise also proved to result in two folds increase in the number of sRCA products detected. By combining sRCA with in situ sequencing for highly multiplex detection in tissue a four-time increase was seen. In summary, we demonstrate that sRCA can significantly increase the performance of padlock-based in situ sequencing for gene expression profiling of tissue sections, enabling detection of low abundant transcripts and the analysis of also highly auto-fluorescent samples. 

  • 1136.
    Wu, Cuiyan
    et al.
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Liu, Huan
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhang, Feng'e
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Shao, Wanzhen
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Yang, Lei
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Ning, Yujie
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Wang, Sen
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhao, Guanghui
    Department of Knee Joint, Xi'an Hong Hui Hospital, Xi'an, P.R. China.
    Lee, Byeong Jae
    Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, Korea.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Guo, Xiong
    Long noncoding RNA expression profile reveals lncRNAs signature associated with extracellular matrix degradation in kashin-beck disease2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17553Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs. We also identified 232 up-regulated and 427 down-regulated mRNAs (≥ 2-fold change). A lncRNA-mRNA correlation analysis combined 343 lncRNAs and 292 mRNAs to form 509 coding-noncoding gene co-expression networks (CNC networks). Eleven lncRNAs were predicted to have cis-regulated target genes, including NAV2 (neuron navigator 2), TOX (thymocyte selection-associated high mobility group box), LAMA4 (laminin, alpha 4), and DEPTOR (DEP domain containing mTOR-interacting protein). The differentially expressed mRNAs in KBD significantly contribute to biological events associated with the extracellular matrix. Meanwhile, 34 mRNAs and 55 co-expressed lncRNAs constituted a network that influences the extracellular matrix. In the network, FBLN1 and LAMA 4 were the core genes with the highest significance. These novel findings indicate that lncRNAs may play a role in extracellular matrix destruction in KBD.

  • 1137. Wu, Xiaofen
    et al.
    Pedersen, Karsten
    Edlund, Johanna
    Eriksson, Lena
    Astrom, Mats
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Bertilsson, Stefan
    Dopson, Mark
    Potential for hydrogen-oxidizing chemolithoautotrophic and diazotrophic populations to initiate biofilm formation in oligotrophic, deep terrestrial subsurface waters2017In: Microbiome, ISSN 0026-2633, E-ISSN 2049-2618, Vol. 5, article id 37Article in journal (Refereed)
    Abstract [en]

    Background: Deep terrestrial biosphere waters are separated from the light-driven surface by the time required to percolate to the subsurface. Despite biofilms being the dominant form of microbial life in many natural environments, they have received little attention in the oligotrophic and anaerobic waters found in deep bedrock fractures. This study is the first to use community DNA sequencing to describe biofilm formation under in situ conditions in the deep terrestrial biosphere. Results: In this study, flow cells were attached to boreholes containing either "modern marine" or "old saline" waters of different origin and degree of isolation from the light-driven surface of the earth. Using 16S rRNA gene sequencing, we showed that planktonic and attached populations were dissimilar while gene frequencies in the metagenomes suggested that hydrogen-fed, carbon dioxide-and nitrogen-fixing populations were responsible for biofilm formation across the two aquifers. Metagenome analyses further suggested that only a subset of the populations were able to attach and produce an extracellular polysaccharide matrix. Initial biofilm formation is thus likely to be mediated by a few bacterial populations which were similar to Epsilonproteobacteria, Deltaproteobacteria, Betaproteobacteria, Verrucomicrobia, and unclassified bacteria. Conclusions: Populations potentially capable of attaching to a surface and to produce extracellular polysaccharide matrix for attachment were identified in the terrestrial deep biosphere. Our results suggest that the biofilm populations were taxonomically distinct from the planktonic community and were enriched in populations with a chemolithoautotrophic and diazotrophic metabolism coupling hydrogen oxidation to energy conservation under oligotrophic conditions.

  • 1138.
    Wuolikainen, Anna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    ALS patients with mutations in the SOD1 gene have an unique metabolomic profile in the cerebrospinal fluid compared with ALS patients without mutations2012In: Molecular Genetics and Metabolism, ISSN 1096-7192, E-ISSN 1096-7206, Vol. 105, no 3, p. 472-478Article in journal (Refereed)
    Abstract [en]

    A specific biochemical marker for early diagnosing and for monitoring disease progression in amyotrophic lateral sclerosis (ALS) will have important clinical applications. ALS is a heterogeneous syndrome with multiple subtypes with ill-defined borders. A minority of patients carries mutations in the Cu/Zn-superoxide dismutase (SOD1) gene but the disease mechanism remains unknown for all types of ALS. Using a GC-TOFMS platform we studied the cerebrospinal fluid (CSF) metabolome in 16 ALS patients with six different mutations in the SOD1 gene and compared with ALS-patients without such mutations. OPLS-DA was used for classification modeling. We find that patients with a SOD1 mutation have a distinct metabolic profile in the CSF. In particular, the eight patients homozygous for the D90A SOD1 mutation showed a distinctively different signature when modeled against ALS patients with other SOD1 mutations and sporadic and familial ALS patients without a SOD1 gene mutation. This was found irrespective of medication with riluzole and survival time. Among the metabolites that contributed most to the CSF signature were arginine, lysine, ornithine, serine, threonine and pyroglutamic acid, all found to be reduced in patients carrying a D90A SOD1 mutation. ALS-patients with a SOD1 gene mutation appear as a distinct metabolic entity in the CSF, in particular in patients with the D90A mutation, the most frequently identified cause of ALS. The findings suggest that metabolomic profiling using GC-TOFMS and multivariate data analysis may be a future tool for diagnosing and monitoring disease progression, and may cast light on the disease mechanisms in ALS.

  • 1139. Wärmländer, Sebastian
    Struktur och dynamik hos DNA studerad med KSR och optisk spektroskopi = Structure and dynamics of DNA studied by NMR and optical spectroscopy2003Doctoral thesis, comprehensive summary (Other academic)
  • 1140. Xenikoudakis, G.
    et al.
    Ersmark, E.
    Tison, J. -L
    Waits, L.
    Kindberg, J.
    Swenson, J. E.
    Dalen, L.
    Consequences of a demographic bottleneck on geneticstructure and variation in the Scandinavian brown bear2015In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 24, no 13, p. 3441-3454Article in journal (Refereed)
  • 1141. Xie, Peiwu
    et al.
    Tu, Tieyao
    Razafimandimbison, Sylvain G.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Faculty of Science, The Bergius Botanical Garden Museum.
    Zhu, Chengjie
    Zhang, Dianxiang
    Phylogenetic position of Guihaiothamnus (Rubiaceae): Its evolutionary and ecological implications2014In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 78, p. 375-385Article in journal (Refereed)
    Abstract [en]

    Guihaiothamnus (Rubiaceae) is an enigmatic, monotypic genus endemic to southwestern China. Its generic status has never been doubted because it is morphologically unique by having rosette habit, showy, long-corolla-tubed flowers, and multi-seeded indehiscent berry-like fruits. The genus has been postulated to be a relict in the broad-leaved forests of China, and to be related to the genus Wendlandia, which was placed in the subfamily Cinchonoideae and recently classified in the tribe Augusteae of the subfamily Dialypetalanthoideae. Using combined evidence from palynology, cytology, and DNA sequences of nuclear ITS and four plastid markers (rps16, trnT-F, ndhF, rbcL), we assessed the phylogenetic position of Guihaiothamnus in Rubiaceae. Our molecular phylogenetic analyses placed the genus deeply nested within Wendlandia. This relationship is corroborated by evidence from palynology and cytology. Using a relaxed molecular clock method based on five fossil records, we dated the stem age of Wendlandia to be 17.46 my and, the split between G. acaulis and related Wendlandia species in southwestern China to be 2.11 mya. This young age, coupled with the derived position in Wendlandia, suggests an evolutionary derivation rather than an evolutionary relict of G. acaulis. Its rosette habit and large showy flowers, which are very distinctive from other Wendlandias, are interpreted as a result of recent rapid adaptation to rock and cliff habitats.

  • 1142. Xing, Fangqian
    et al.
    Mao, Jian-Feng
    Meng, Jingxiang
    Dai, Jianfeng
    Zhao, Wei
    Liu, Hao
    Xing, Zhen
    Zhang, Hua
    Wang, Xiao-Ru
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Li, Yue
    Needle morphological evidence of the homoploid hybrid origin of Pinus densata based on analysis of artificial hybrids and the putative parents, Pinus tabuliformis and Pinus yunnanensis2014In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 4, no 10, p. 1890-1902Article in journal (Refereed)
    Abstract [en]

    Genetic analyses indicate that Pinus densata is a natural homoploid hybrid originating from Pinus tabuliformis and Pinus yunnanensis. Needle morphological and anatomical features show relative species stability and can be used to identify coniferous species. Comparative analyses of these needle characteristics and phenotypic differences between the artificial hybrids, P.densata, and parental species can be used to determine the genetic and phenotypic evolutionary consequences of natural hybridization. Twelve artificial hybrid families, the two parental species, and P.densata were seeded in a high-altitude habitat in Linzhi, Tibet. The needles of artificial hybrids and the three pine species were collected, and 24 needle morphological and anatomical traits were analyzed. Based on these results, variations in 10 needle traits among artificial hybrid families and 22 traits among species and artificial hybrids were predicted and found to be under moderate genetic control. Nineteen needle traits in artificial hybrids were similar to those in P.densata and between the two parental species, P.tabuliformis and P.yunnanensis. The ratio of plants with three needle clusters in artificial hybrids was 22.92%, which was very similar to P.densata. The eight needle traits (needle length, the mean number of stomata in sections 2mm in length of the convex and flat sides of the needle, mean stomatal density, mesophyll/vascular bundle area ratio, mesophyll/resin canal area ratio, mesophyll/(resin canals and vascular bundles) area ratio, vascular bundle/resin canal area ratio) relative to physiological adaptability were similar to the artificial hybrids and P.densata. The similar needle features between the artificial hybrids and P.densata could be used to verify the homoploid hybrid origin of P.densata and helps to better understand of the hybridization roles in adaptation and speciation in plants.

  • 1143.
    Xochelli, Aliki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. ..
    Kavakiotis, Ioannis
    Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece..
    Agathangelidis, Andreas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Ntoufa, Stavroula
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Tausch, Eugen
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Yan, Xiao-Jie
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, Tait
    Mayo Clin, Dept Med, Dept Hematol, Rochester, MN USA..
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Boudjogra, Myriam
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Rossi, Davide
    Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Navarro, Alba
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain..
    Sandberg, Yorick
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, Fie Juhl
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Scarfo, Lydia
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Sudarikov, Andrey
    Natl Res Ctr Hematol, Moscow, Russia..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy..
    Tzenou, Tatiana
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Karan-Djurasevic, Teodora
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Catherwood, Mark
    Belfast City Hosp, Dept Haematooncol, Belfast, Antrim, North Ireland..
    Kienle, Dirk
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Chatzouli, Maria
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Facco, Monica
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Bahlo, Jasmin
    Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany..
    Pott, Christiane
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Pedersen, Lone Bredo
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Chu, Charles C.
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Giudicelli, Veronique
    Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France..
    Lefranc, Marie-Paule
    Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Vlahavas, Ioannis
    Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece..
    Antic, Darko
    Ctr Clin, Clin Hematol, Belgrade, Serbia.;Univ Belgrade, Fac Med, Belgrade, Serbia..
    Trentin, Livio
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Montillo, Marco
    Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy..
    Niemann, Carsten
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Doehner, Hartmut
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Langerak, Anton W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Hallek, Michael
    Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany..
    Campo, Elias
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain..
    Chiorazzi, Nicholas
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Maglaveras, Nikos
    Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Gaidano, Gianluca
    Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy..
    Jelinek, Diane F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Stilgenbauer, Stephan
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Chouvarda, Ioanna
    Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Hadzidimitriou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Ist Sci San Raffaele, Milan, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece ;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 17, p. 5292-5301Article in journal (Refereed)
    Abstract [en]

    Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.  

  • 1144.
    Xu, Dongqing
    et al.
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.;Gothenburg Univ, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Lin, Fang
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China..
    Jiang, Yan
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.;Gothenburg Univ, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Ling, Junjie
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China..
    Hettiarachchi, Chamari
    Univ Colombo, Dept Chem, Colombo, Sri Lanka..
    Tellgren-Roth, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Holm, Magnus
    Gothenburg Univ, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Wei, Ning
    Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA..
    Deng, Xing Wang
    Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Adv Agr Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.;Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China..
    Arabidopsis COP1 SUPPRESSOR 2 Represses COP1 E3 Ubiquitin Ligase Activity through Their Coiled-Coil Domains Association2015In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 12, article id e1005747Article in journal (Refereed)
    Abstract [en]

    CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) functions as an E3 ubiquitin ligase and mediates a variety of developmental processes in Arabidopsis by targeting a number of key regulators for ubiquitination and degradation. Here, we identify a novel COP1 interacting protein, COP1 SUPPRESSOR 2 (CSU2). Loss of function mutations in CSU2 suppress the constitutive photomorphogenic phenotype of cop1-6 in darkness. CSU2 directly interacts with COP1 via their coiled-coil domains and is recruited by COP1 into nuclear speckles in living plant cells. Furthermore, CSU2 inhibits COP1 E3 ubiquitin ligase activity in vitro, and represses COP1 mediated turnover of HY5 in cell-free extracts. We propose that in csu2 cop1-6 mutants, the lack of CSU2's repression of COP1 allows the low level of COP1 to exhibit higher activity that is sufficient to prevent accumulation of HY5 in the dark, thus restoring the etiolated phenotype. In addition, CSU2 is required for primary root development under normal light growth condition.

  • 1145.
    Xu, Feifei
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jerlström-Hultqvist, Jon
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Einarsson, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Astvaldsson, Asgeir
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Svärd, Staffan G
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Andersson, Jan O
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments2014In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 2, p. e1004053-Article in journal (Refereed)
    Abstract [en]

    Spironucleus salmonicida causes systemic infections in salmonid fish. It belongs to the group diplomonads, binucleated heterotrophic flagellates adapted to micro-aerobic environments. Recently we identified energy-producing hydrogenosomes in S. salmonicida. Here we present a genome analysis of the fish parasite with a focus on the comparison to the more studied diplomonad Giardia intestinalis. We annotated 8067 protein coding genes in the ∼12.9 Mbp S. salmonicida genome. Unlike G. intestinalis, promoter-like motifs were found upstream of genes which are correlated with gene expression, suggesting a more elaborate transcriptional regulation. S. salmonicida can utilise more carbohydrates as energy sources, has an extended amino acid and sulfur metabolism, and more enzymes involved in scavenging of reactive oxygen species compared to G. intestinalis. Both genomes have large families of cysteine-rich membrane proteins. A cluster analysis indicated large divergence of these families in the two diplomonads. Nevertheless, one of S. salmonicida cysteine-rich proteins was localised to the plasma membrane similar to G. intestinalis variant-surface proteins. We identified S. salmonicida homologs to cyst wall proteins and showed that one of these is functional when expressed in Giardia. This suggests that the fish parasite is transmitted as a cyst between hosts. The extended metabolic repertoire and more extensive gene regulation compared to G. intestinalis suggest that the fish parasite is more adapted to cope with environmental fluctuations. Our genome analyses indicate that S. salmonicida is a well-adapted pathogen that can colonize different sites in the host.

  • 1146. Xue, Weiya
    et al.
    Ruprecht, Colin
    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).
    Hematy, Kian
    Chang, Christine
    Frommer, Wolf B
    Persson, Staffan
    Niittyla, Totte
    Paramutation-like interaction of T-DNA loci in arabidopsis2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e51651-Article in journal (Refereed)
    Abstract [en]

    In paramutation, epigenetic information is transferred from one allele to another to create a gene expression state which is stably inherited over generations. Typically, paramutation describes a phenomenon where one allele of a gene down-regulates the expression of another allele. Paramutation has been described in several eukaryotes and is best understood in plants. Here we describe an unexpected paramutation-like trans SALK T-DNA interaction in Arabidopsis. Unlike most of the previously described paramutations, which led to gene silencing, the trans SALK T-DNA interaction caused an increase in the transcript levels of the endogenous gene (COBRA) where the T-DNA was inserted. This increased COBRA expression state was stably inherited for several generations and led to the partial suppression of the cobra phenotype. DNA methylation was implicated in this trans SALK T-DNA interaction since mutation of the DNA methyltransferase 1 in the suppressed cobra caused a reversal of the suppression. In addition, null mutants of the DNA demethylase ROS1 caused a similar COBRA transcript increase in the cobra SALK T-DNA mutant as the trans T-DNA interaction. Our results provide a new example of a paramutation-like trans T-DNA interaction in Arabidopsis, and establish a convenient hypocotyl elongation assay to study this phenomenon. The results also alert to the possibility of unexpected endogenous transcript increase when two T-DNAs are combined in the same genetic background. Citation: Xue W, Ruprecht C, Street N, Hematy K, Chang C, et al. (2012) Paramutation-Like Interaction of T-DNA Loci in Arabidopsis. PLoS ONE 7(12): e51651. doi:10.1371/journal.pone.0051651

  • 1147.
    Xue-Franzen, Yongtao
    et al.
    Södertörn University, School of Life Sciences. Karolinska Institutet.
    Kjaerulff, Soren
    University of Copenhagen, Copenhagen, Denmark.
    Holmberg, Christian
    University of Copenhagen, Copenhagen, Denmark.
    Wright, Anthony
    Södertörn University, School of Life Sciences. Karolinska Institutet.
    Nielsen, Olaf
    University of Copenhagen, Copenhagen, Denmark.
    Genomewide identification of pheromone-targeted transcription in fission yeast2006In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 7, p. 303-, article id 303Article in journal (Refereed)
    Abstract [en]

    Background: Fission yeast cells undergo sexual differentiation in response to nitrogen starvation. In this process haploid M and P cells first mate to form diploid zygotes, which then enter meiosis and sporulate. Prior to mating, M and P cells communicate with diffusible mating pheromones that activate a signal transduction pathway in the opposite cell type. The pheromone signalling orchestrates mating and is also required for entry into meiosis. Results: Here we use DNA microarrays to identify genes that are induced by M-factor in P cells and by P-factor in M-cells. The use of a cyr1 genetic background allowed us to study pheromone signalling independently of nitrogen starvation. We identified a total of 163 genes that were consistently induced more than two-fold by pheromone stimulation. Gene disruption experiments demonstrated the involvement of newly discovered pheromone-induced genes in the differentiation process. We have mapped Gene Ontology ( GO) categories specifically associated with pheromone induction. A direct comparison of the M- and P-factor induced expression pattern allowed us to identify cell-type specific transcripts, including three new M- specific genes and one new P-specific gene. Conclusion: We found that the pheromone response was very similar in M and P cells. Surprisingly, pheromone control extended to genes fulfilling their function well beyond the point of entry into meiosis, including numerous genes required for meiotic recombination. Our results suggest that the SteII transcription factor is responsible for the majority of pheromone-induced transcription. Finally, most cell-type specific genes now appear to be identified in fission yeast.

  • 1148. Xun, Wei Wei
    et al.
    Brennan, Paul
    Tjonneland, Anne
    Vogel, Ulla
    Overvad, Kim
    Kaaks, Rudolf
    Canzian, Federico
    Boeing, Heiner
    Trichopoulou, Antonia
    Oustoglou, Erifili
    Giotaki, Zoi
    Johansson, Mattias
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H M
    Lund, Eiliv
    Kumle, Merethe
    Rodríguez, Laudina
    Agudo, Antonio
    Sánchez, Maria-José
    Arriola, Larraitz
    Chirlaque, María-Dolores
    Barricarte, Aurelio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Key, Tim
    Riboli, Elio
    Vineis, Paolo
    Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC).2011In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 26, no 5, p. 657-666Article in journal (Refereed)
    Abstract [en]

    The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

  • 1149.
    Yazdi, Homa Papoli
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Old but Not (So) Degenerated-Slow Evolution of Largely Homomorphic Sex Chromosomes in Ratites2014In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, no 6, p. 1444-1453Article in journal (Refereed)
    Abstract [en]

    Degeneration of the nonrecombining chromosome is a common feature of sex chromosome evolution, readily evident by the presence of a pair of largely heteromorphic chromosomes, like in eutherian mammals and birds. However, in ratites (order Palaeognathae, including, e.g., ostrich), the Z and W chromosomes are similar in size and largely undifferentiated, despite avian sex chromosome evolution was initiated > 130 Ma. To better understand what may limit sex chromosome evolution, we performed ostrich transcriptome sequencing and studied genes from the nonrecombining region of the W chromosome. Fourteen gametologous gene pairs present on the W chromosome and Z chromosome were identified, with synonymous sequence divergence of 0.027-0.177. The location of these genes on the Z chromosome was consistent with a sequential increase in divergence, starting 110-157 and ending 24-30 Ma. On the basis of the occurrence of Z-linked genes hemizygous in females, we estimate that about one-third of the Z chromosome does not recombine with the W chromosome in female meiosis. Pairwise d(N)/d(S) between gametologs decreased with age, suggesting strong evolutionary constraint in old gametologs. Lineage-specific d(N)/d(S) was consistently higher in W-linked genes, in accordance with the lower efficacy of selection expected in nonrecombining chromosomes. A higher ratio of GC > AT:AT > GC substitutions in W-linked genes supports a role for GC-biased gene conversion in differentially driving base composition on the two sex chromosomes. A male-to-female (M:F) expression ratio of close to one for recombining genes and close to two for Z-linked genes lacking a W copy show that dosage compensation is essentially absent. Some gametologous genes have retained active expression of the W copy in females (giving a M:F ratio of 1 for the gametologous gene pair), whereas for others W expression has become severely reduced resulting in a M:F ratio of close to 2. These observations resemble the patterns of sex chromosome evolution seen in other avian and mammalian lineages, suggesting similar underlying evolutionary processes, although the rate of sex chromosome differentiation has been atypically low. Lack of dosage compensation may be a factor hindering sex chromosome evolution in this lineage.

  • 1150.
    Yurova Axelsson, Ekaterina
    Linnaeus University, Faculty of Technology, Department of Mathematics.
    On the representation of the genetic code by the attractors of 2-adic function2015In: Physica scripta. T, ISSN 0281-1847, Vol. 2015, no T 165, article id 014043Article in journal (Refereed)
    Abstract [en]

    The genetic code is a map which gives the correspondence between codons in DNA and amino acids. As a continuation of the study made by Khrennikov and Kozyrev on the genetic code, we consider a construction, where amino acids are associated to the attractors of some two-adic function. In this paper, we give an explicit form of representations for the standard nuclear and vertebrate mitochondrial genetics codes. To set these functions we use a van der Put representation. The usage of the van der Put series reduces the complexity of computation for explicit form of the functions for the genetic codes.

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