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Publications (10 of 37) Show all publications
Lundberg, M., Liedvogel, M., Larson, K., Sigeman, H., Grahn, M., Wright, A. P., . . . Bensch, S. (2017). Genetic differences between willow warbler migratory phenotypes are few and cluster in large haplotype blocks [Letter to the editor]. Evolution Letters, 1(3), 155-168
Open this publication in new window or tab >>Genetic differences between willow warbler migratory phenotypes are few and cluster in large haplotype blocks
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2017 (English)In: Evolution Letters, ISSN 2056-3744, Vol. 1, no 3, p. 155-168Article in journal, Letter (Refereed) Published
Abstract [en]

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

Keywords
Divergent chromosome region, local adaptation, migration
National Category
Evolutionary Biology
Research subject
Environmental Studies; Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-34253 (URN)10.1002/evl3.15 (DOI)000449440100004 ()
Projects
Molecular mechanisms for recent acquisition of alternative winter-migration behavior in songbirds of the Baltic Sea Region
Funder
The Foundation for Baltic and East European Studies, A067-08
Available from: 2018-01-17 Created: 2018-01-17 Last updated: 2018-11-30Bibliographically approved
Lundberg, M., Boss, J., Canbäck, B., Liedvogel, M., Larson, K. W., Grahn, M., . . . Wright, A. P. (2013). Characterisation of a transcriptome to find sequence differences between two differentially migrating subspecies of the willow warbler Phylloscopus trochilus.. BMC Genomics, 14, Article ID 330.
Open this publication in new window or tab >>Characterisation of a transcriptome to find sequence differences between two differentially migrating subspecies of the willow warbler Phylloscopus trochilus.
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2013 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 14, article id 330Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Animal migration requires adaptations in morphological, physiological and behavioural traits. Several of these traits have been shown to possess a strong heritable component in birds, but little is known about their genetic architecture. Here we used 454 sequencing of brain-derived transcriptomes from two differentially migrating subspecies of the willow warbler Phylloscopus trochilus to detect genes potentially underlying traits associated with migration.

RESULTS: The transcriptome sequencing resulted in 1.8 million reads following filtering steps. Most of the reads (84%) were successfully mapped to the genome of the zebra finch Taeniopygia gutatta. The mapped reads were situated within at least 12,101 predicted zebra finch genes, with the greatest sequencing depth in exons. Reads that were mapped to intergenic regions were generally located close to predicted genes and possibly located in uncharacterized untranslated regions (UTRs). Out of 85,000 single nucleotide polymorphisms (SNPs) with a minimum sequencing depth of eight reads from each of two subspecies-specific pools, only 55 showed high differentiation, confirming previous studies showing that most of the genetic variation is shared between the subspecies. Validation of a subset of the most highly differentiated SNPs using Sanger sequencing demonstrated that several of them also were differentiated between an independent set of individuals of each subspecies. These SNPs were clustered in two chromosome regions that are likely to be influenced by divergent selection between the subspecies and that could potentially be associated with adaptations to their different migratory strategies.

CONCLUSIONS: Our study represents the first large-scale sequencing analysis aiming at detecting genes underlying migratory phenotypes in birds and provides new candidates for genes potentially involved in migration.

National Category
Ecology
Research subject
Environmental Studies
Identifiers
urn:nbn:se:sh:diva-18923 (URN)10.1186/1471-2164-14-330 (DOI)000319226500002 ()23672489 (PubMedID)2-s2.0-84877605906 (Scopus ID)
Projects
Molecular mechanisms for recent acquisition of alternative winter-migration behavior in songbirds of the Baltic Sea Region
Funder
The Foundation for Baltic and East European Studies, A067-08Swedish Research Council, 349-2007-8690
Available from: 2013-05-23 Created: 2013-05-23 Last updated: 2017-12-06Bibliographically approved
Nilsson, J., Grahn, M. & Wright, A. P. (2011). Proteome-wide evidence for enhanced positive Darwinian selection within intrinsically disordered regions in proteins. Genome Biology, 12(7), R65
Open this publication in new window or tab >>Proteome-wide evidence for enhanced positive Darwinian selection within intrinsically disordered regions in proteins
2011 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 12, no 7, p. R65-Article in journal (Refereed) Published
Abstract [en]

ABSTRACT: BACKGROUND: Understanding the adaptive changes that alter the function of proteins during evolution is an important question for biology and medicine. The increasing number of completely sequenced genomes from closely related organisms, as well as individuals within species, facilitates systematic detection of recent selection events by means of comparative genomics. RESULTS: We have used genome-wide strain-specific single nucleotide polymorphism data from 64 strains of budding yeast (Saccharomyces cerevisiae or Saccharomyces paradoxus) to determine whether adaptive positive selection is correlated with protein regions showing propensity for different classes of structure conformation. Data from phylogenetic and population genetic analysis of 3746 gene alignments consistently shows a significantly higher degree of positive Darwinian selection in intrinsically disordered regions of proteins compared to regions of alpha helix, beta sheet or tertiary structure. Evidence of positive selection is significantly enriched in classes of proteins whose functions and molecular mechanisms can be coupled to adaptive processes and these classes tend to have a higher average content of intrinsically unstructured protein regions. CONCLUSIONS: We suggest that intrinsically disordered protein regions may be important for the production and maintenance of genetic variation with adaptive potential and that they may thus be of central significance for the evolvability of the organism or cell in which they occur.

National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:sh:diva-9985 (URN)10.1186/gb-2011-12-7-r65 (DOI)000296648400004 ()21771306 (PubMedID)2-s2.0-79960555958 (Scopus ID)
Available from: 2011-09-05 Created: 2011-07-27 Last updated: 2017-07-17Bibliographically approved
Nugent, R. L., Johnsson, A., Fleharty, B., Gogol, M., Xue-Franzen, Y., Seidel, C., . . . Forsburg, S. L. (2010). Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation. BMC Genomics, 11, Article ID 59.
Open this publication in new window or tab >>Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation
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2010 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 11, article id 59Article in journal (Refereed) Published
Abstract [en]

Background: Histone acetyltransferase enzymes (HATs) are implicated in egulation of transcription. HATs from different families may overlap in arget and substrate specificity. esults: We isolated the elp3(+) gene encoding the histone cetyltransferase subunit of the Elongator complex in fission yeast and haracterized the phenotype of an Delta elp3 mutant. We examined genetic nteractions between Delta elp3 and two other HAT mutants, Delta mst2 nd Delta gcn5 and used whole genome microarray analysis to analyze heir effects on gene expression. onclusions: Comparison of phenotypes and expression profiles in single, ouble and triple mutants indicate that these HAT enzymes have verlapping functions. Consistent with this, overlapping specificity in istone H3 acetylation is observed. However, there is no evidence for verlap with another HAT enzyme, encoded by the essential mst1(+) gene.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:sh:diva-13716 (URN)10.1186/1471-2164-11-59 (DOI)000274660300002 ()20096118 (PubMedID)2-s2.0-76949101471 (Scopus ID)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Expression profiling of S. pombe acetyltransferase identifies redundant pathways of gene regulation

Available from: 2011-12-06 Created: 2011-12-06 Last updated: 2017-12-08Bibliographically approved
Xue-Franzen, Y., Johnsson, A., Brodin, D., Henriksson, J., Bürglin, T. R. & Wright, A. P. H. (2010). Genome-wide characterisation of the Gcn5 histone acetyltransferase in budding yeast during stress adaptation reveals evolutionarily conserved and diverged roles. BMC Genomics, 11, Article ID 200.
Open this publication in new window or tab >>Genome-wide characterisation of the Gcn5 histone acetyltransferase in budding yeast during stress adaptation reveals evolutionarily conserved and diverged roles
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2010 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 11, article id 200Article in journal (Refereed) Published
Abstract [en]

Background: Gcn5 is a transcriptional coactivator with histone cetyltransferase activity that is conserved with regard to structure as ell as its histone substrates throughout the eukaryotes. Gene egulatory networks within cells are thought to be evolutionarily iverged. The use of evolutionarily divergent yeast species, such as S. erevisiae and S. pombe, which can be studied under similar nvironmental conditions, provides an opportunity to examine the nterface between conserved regulatory components and their cellular pplications in different organisms. esults: We show that Gcn5 is important for a common set of stress esponses in evolutionarily diverged yeast species and that the activity f the conserved histone acetyltransferase domain is required. We define group of KCl stress response genes in S. cerevisiae that are pecifically dependent on Gcn5. Gcn5 is localised to many Gcn5-dependent enes including Gcn5 repressed targets such as FLO8. Gcn5 regulates ivergent sets of KCl responsive genes in S. cerevisiae and S. pombe. enome-wide localization studies showed a tendency for redistribution of cn5 during KCl stress adaptation in S. cerevisiae from short genes to he transcribed regions of long genes. An analogous redistribution was ot observed in S. pombe. onclusions: Gcn5 is required for the regulation of divergent sets of Cl stress-response genes in S. cerevisiae and S. pombe even though it s required a common group of stress responses, including the response o KCl. Genes that are physically associated with Gcn5 require its ctivity for their repression or activation during stress adaptation, roviding support for a role of Gcn5 as a corepressor as well as a oactivator. The tendency of Gcn5 to re-localise to the transcribed egions of long genes during KCl stress adaptation suggests that Gcn5 lays a specific role in the expression of long genes under adaptive onditions, perhaps by regulating transcriptional elongation as has been een for Gcn5 in S. pombe. Interestingly an analogous redistribution of cn5 is not seen in S. pombe. The study thus provides important new nsights in relation to why coregulators like Gcn5 are required for the orrect expression of some genes but not others.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:sh:diva-13712 (URN)10.1186/1471-2164-11-200 (DOI)000277270600002 ()20338033 (PubMedID)2-s2.0-77952260641 (Scopus ID)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Functional aspects of the Gcn5 histone acetyltransferase in stress responses of evolutionarily diverged yest species

Available from: 2011-12-06 Created: 2011-12-06 Last updated: 2017-12-08Bibliographically approved
Shiue, C.-N., Arabi, A. & Wright, A. P. (2010). Nucleolar organization, growth control and cancer. Epigenetics, 5(3), 200-205
Open this publication in new window or tab >>Nucleolar organization, growth control and cancer
2010 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 5, no 3, p. 200-205Article in journal (Refereed) Published
Abstract [en]

The nucleolus is a dynamic region of the nucleus that is disassembled and reformed each cell cycle and whose size is correlated with cell growth rate. Nucleolar size is a prognostic measure of cancer disease severity and increasing evidence suggests a causative role of nucleolar lesions in many cancers. In recent work (Shiue et al. Oncogene 28, 1833-42, 2009) we showed that the c-Myc oncoprotein induces changes in the higher order structure of rDNA chromatin in the nucleolus of growth stimulated quiescent rat cells. Here we show that c-Myc induces similar changes in human cells, that c-Myc plays a role in the overall structural integrity of the nucleolus and that c-Myc and its antagonistic partner Mad1 interact to program the epigenetic status of rDNA chromatin. These changes are discussed in relation to current knowledge about nucleolar structure as well as the organization of chromosomes and transcription factories in nuclear regions outside the nucleolus.

National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-30691 (URN)10.4161/epi.5.3.11376 (DOI)000276196400006 ()20305389 (PubMedID)2-s2.0-77954672013 (Scopus ID)
Funder
The Foundation for Baltic and East European StudiesSwedish Research CouncilSwedish Cancer Society
Available from: 2016-08-04 Created: 2016-08-04 Last updated: 2017-11-28Bibliographically approved
Johnsson, A. E. & Wright, A. P. H. (2010). The role of specific HAT-HDAC interactions in transcriptional elongation. Cell Cycle, 9(3), 467-471
Open this publication in new window or tab >>The role of specific HAT-HDAC interactions in transcriptional elongation
2010 (English)In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 9, no 3, p. 467-471Article in journal (Refereed) Published
Abstract [en]

We previously reported genome-wide evidence that the Gcn5 histone cetyltransferase (HAT) is located in the transcribed region of highly xpressed genes and that it plays an important role in transcriptional longation in the fission yeast, Schizosaccharomyces pombe (EMBO Reports 009; 10: 1009-14). Furthermore, the specific interplay between Gcn5 and he Clr3 histone deacetylase (HDAC) controls the acetylation levels of ysine-14 in histone H3 in the same class of highly expressed genes. utants of histone H3 that cannot be acetylated at residue 14 show imilar stress phenotypes to those observed for mutants lacking Gcn5. In his Extra View article we review these findings in relation to related iterature and extend important aspects of the original study. Notably, cn5 and Gcn5-dependent acetylation of histone H3K14 tend to be more nriched in the upstream regions of genes that require Gcn5 for correct xpression compared to genes that are independent of Gcn5. This suggests critical role of Gcn5 in the transcriptional initiation of these enes. Gcn5 is however most highly enriched in the transcribed regions f these gene sets but there is no difference between Gcn5-dependent and cn5-independent gene sets. Thus we suggest that Gcn5 plays an important ut redundant role in the transcriptional elongation of these genes. The ir2 HDAC has a similar genomic localization and enzymatic activity to lr3. We studied gcn5 Delta sir2 Delta double mutants that do not show a uppressed phenotype in relation to gcn5 Delta single mutants, compared o gcn5 Delta clr3 Delta mutants that do, in order to better understand he specificity of the interplay between Gcn5 and Clr3. In some classes f non-highly expressed genes the clr3 Delta mutant tends to restore evels of histone H3K14 acetylation in the double mutant strain more ffectively than sir2 Delta.

National Category
Cell Biology
Identifiers
urn:nbn:se:sh:diva-13714 (URN)10.4161/cc.9.3.10543 (DOI)000274140000023 ()20081370 (PubMedID)2-s2.0-77951905249 (Scopus ID)
Available from: 2011-12-06 Created: 2011-12-06 Last updated: 2017-12-08Bibliographically approved
Ferreira, M. E., Berndt, K. D., Nilsson, J. & Wright, A. P. H. (2010). WD40 Domain Divergence Is Important for Functional Differences between he Fission Yeast Tup11 and Tup12 Co-Repressor Proteins. PLoS ONE, 5(6), Article ID e11009.
Open this publication in new window or tab >>WD40 Domain Divergence Is Important for Functional Differences between he Fission Yeast Tup11 and Tup12 Co-Repressor Proteins
2010 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 6, article id e11009Article in journal (Refereed) Published
Abstract [en]

We have previously demonstrated that subsets of Ssn6/Tup target genes ave distinct requirements for the Schizosaccharomyces pombe homologs of he Tup1/Groucho/TLE co-repressor proteins, Tup11 and Tup12. The very igh level of divergence in the histone interacting repression domains f the two proteins suggested that determinants distinguishing Tup11 and up12 might be located in this domain. Here we have combined hylogenetic and structural analysis as well as phenotypic haracterization, under stress conditions that specifically require up12, to identify and characterize the domains involved in up12-specific action. The results indicate that divergence in the epression domain is not generally relevant for Tup12-specific function. nstead, we show that the more highly conserved C-terminal WD40 repeat omain of Tup12 is important for Tup12-specific function. Surface amino cid residues specific for the WD40 repeat domain of Tup12 proteins in ifferent fission yeasts are clustered in blade 3 of the propeller-like tructure that is characteristic of WD40 repeat domains. The Tup11 and up12 proteins in fission yeasts thus provide an excellent model system or studying the functional divergence of WD40 repeat domains.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-13706 (URN)10.1371/journal.pone.0011009 (DOI)000278494900021 ()2-s2.0-77955193861 (Scopus ID)
Available from: 2011-12-06 Created: 2011-12-06 Last updated: 2018-12-17Bibliographically approved
Ferreira, M. E., Prochasson, P., Berndt, K. D., Workman, J. L. & Wright, A. P. H. (2009). Activator-binding domains of the SWI/SNF chromatin remodeling complex characterized in vitro are required for its recruitment to promoters in vivo. The FEBS Journal, 276(9), 2557-2565
Open this publication in new window or tab >>Activator-binding domains of the SWI/SNF chromatin remodeling complex characterized in vitro are required for its recruitment to promoters in vivo
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2009 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 9, p. 2557-2565Article in journal (Refereed) Published
Abstract [en]

Interaction between acidic activation domains and the activator-binding domains of Swi1 and Snf5 of the yeast SWI/SNF chromatin remodeling complex has previously been characterized in vitro. Although deletion of both activator-binding domains leads to phenotypes that differ from the wild-type, their relative importance for SWI/SNF recruitment to target genes has not been investigated. In the present study, we used chromatin immunoprecipitation assays to investigate the individual and collective importance of the activator-binding domains for SWI/SNF recruitment to genes within the GAL regulon in vivo. We also investigated the consequences of defective SWI/SNF recruitment for target gene activation. We demonstrate that deletion of both activator-binding domains essentially abolishes galactose-induced SWI/SNF recruitment and causes a reduction in transcriptional activation similar in magnitude to that associated with a complete loss of SWI/SNF activity. The activator-binding domains in Swi1 and Snf5 make approximately equal contributions to the recruitment of SWI/SNF to each of the genes studied. The requirement for SWI/SNF recruitment correlates with GAL genes that are highly and rapidly induced by galactose.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-13900 (URN)10.1111/j.1742-4658.2009.06979.x (DOI)000264882700012 ()19476494 (PubMedID)2-s2.0-64149100814 (Scopus ID)
Available from: 2011-12-14 Created: 2011-12-14 Last updated: 2017-12-08Bibliographically approved
Shiue, C. N., Berkson, R. G. & Wright, A. P. (2009). c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells. Oncogene, 28(16), 1833-1842
Open this publication in new window or tab >>c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells
2009 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 28, no 16, p. 1833-1842Article in journal (Refereed) Published
Abstract [en]

c-Myc is an oncogenic transcription factor capable of activating transcription by all three nuclear RNA polymerases, thus acting as a high-level coordinator of protein synthesis capacity and cell growth rate. c-Myc recruits RNA polymerase I-related transcription factors to the rDNA when quiescent cells are stimulated to re-enter the cell cycle. Using a model system of cell lines with variable c-Myc status, we show that on stimulation c-Myc rapidly induces gene loop structures in rDNA chromatin that juxtapose upstream and downstream rDNA sequences. c-Myc activation is both necessary and sufficient for this change in rDNA chromatin conformation. c-Myc activation induces association of TTF-1 with the rDNA, and c-Myc is physically associated with induced rDNA gene loops. The origins of two or more rDNA gene loops are closely juxtaposed, suggesting the possibility that c-Myc induces nucleolar chromatin hubs. Induction of rDNA gene loops may be an early step in the reprogramming of quiescent cells as they re-enter the growth cycle.

Keywords
c-Myc, nucleolus, transcription, ribosome biogenesis, RNA polymerase I
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
urn:nbn:se:sh:diva-17673 (URN)10.1038/onc.2009.21 (DOI)000265640500002 ()19270725 (PubMedID)2-s2.0-67349121053 (Scopus ID)
Available from: 2012-12-14 Created: 2012-12-14 Last updated: 2017-12-06Bibliographically approved
Projects
Molecular mechanisms for recent acquisition of alternative winter-migration behavior in songbirds of the Baltic Sea Region [A067-2008_OSS]; Södertörn University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1029-9969

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