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Sundström, Görel
Publications (10 of 17) Show all publications
Xu, B., Bergqvist, C. A., Sundström, G., Lundell, I., Vaudry, H., Leprince, J. & Larhammar, D. (2015). Characterization of peptide QRFP (26RFa) and its receptor from amphioxus, Branchiostoma floridae. General and Comparative Endocrinology, 210, 107-113
Open this publication in new window or tab >>Characterization of peptide QRFP (26RFa) and its receptor from amphioxus, Branchiostoma floridae
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2015 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 210, p. 107-113Article in journal (Refereed) Published
Abstract [en]

A peptide ending with RFamide (Arg-Phe-amide) was discovered independently by three different laboratories in 2003 and named 26RFa or QRFP. In mammals, a longer version of the peptide, 43 amino acids, was identified and found to bind to the orphan G protein-coupled receptor GPR103. We searched the genome database of Branchiostoma floridae (Bfl) for receptor sequences related to those that bind peptides ending with RFa or RYa (including receptors for NPFF, PRLH, GnIH, and NPY). One receptor clustered in phylogenetic analyses with mammalian QRFP receptors. The gene has 3 introns in Bfl and 5 in human, but all intron positions differ, implying that the introns were inserted independently. A QRFP-like peptide consisting of 25 amino acids and ending with RFa was identified in the amphioxus genome. Eight of the ten last amino acids are identical between Bfl and human. The prepro-QRFP gene in Bfl has one intron in the propeptide whereas the human gene lacks introns. The Bfl QRFP peptide was synthesized and the receptor was functionally expressed in human cells. The response was measured as inositol phosphate (IP) turnover. The Bfl QRFP peptide was found to potently stimulate the receptor's ability to induce IP turnover with an EC50 of 0.28nM. Also the human QRFP peptides with 26 and 43 amino acids were found to stimulate the receptor (1.9 and 5.1nM, respectively). Human QRFP with 26 amino acids without the carboxyterminal amide had dramatically lower potency at 1.3μM. Thus, we have identified an amphioxus QRFP-related peptide and a corresponding receptor and shown that they interact to give a functional response.

Keywords
Neuropeptide, receptor, evolution
National Category
Neurosciences
Research subject
Evolutionary Genetics; Neuroscience
Identifiers
urn:nbn:se:uu:diva-240039 (URN)10.1016/j.ygcen.2014.10.010 (DOI)000346886400012 ()25449662 (PubMedID)
Available from: 2015-01-05 Created: 2015-01-05 Last updated: 2019-01-03Bibliographically approved
Krogvold, L., Skog, O., Sundström, G., Edwin, B., Buanes, T., Hanssen, K. F., . . . Dahl-Jorgensen, K. (2015). Function of Isolated Pancreatic Islets From Patients at Onset of Type 1 Diabetes: Insulin Secretion Can Be Restored After Some Days in a Nondiabetogenic Environment In Vitro: Results From the DiViD Study. Diabetes, 64(7), 2506-2512
Open this publication in new window or tab >>Function of Isolated Pancreatic Islets From Patients at Onset of Type 1 Diabetes: Insulin Secretion Can Be Restored After Some Days in a Nondiabetogenic Environment In Vitro: Results From the DiViD Study
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2015 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, no 7, p. 2506-2512Article in journal (Refereed) Published
Abstract [en]

The understanding of the etiology of type 1 diabetes (T1D) remains limited. One objective of the Diabetes Virus Detection (DiViD) study was to collect pancreatic tissue from living subjects shortly after the diagnosis of T1D. Here we report the insulin secretion ability by in vitro glucose perifusion and explore the expression of insulin pathway genes in isolated islets of Langerhans from these patients. Whole-genome RNA sequencing was performed on islets from six DiViD study patients and two organ donors who died at the onset of T1D, and the findings were compared with those from three nondiabetic organ donors. All human transcripts involved in the insulin pathway were present in the islets at the onset of T1D. Glucose-induced insulin secretion was present in some patients at the onset of T1D, and a perfectly normalized biphasic insulin release was obtained after some days in a nondiabetogenic environment in vitro. This indicates that the potential for endogenous insulin production is good, which could be taken advantage of if the disease process was reversed at diagnosis.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-259101 (URN)10.2337/db14-1911 (DOI)000356934000033 ()25677915 (PubMedID)
Funder
Swedish Diabetes Association
Note

De tre första författarna delar förstaförfattarskapet.

De sista två författarna delar sistaförfattarskapet.

Available from: 2015-07-28 Created: 2015-07-27 Last updated: 2017-12-04Bibliographically approved
Xu, B., Lagman, D., Sundström, G. & Larhammar, D. (2015). Neuropeptide Y family receptors Y1 and Y2 from sea lamprey, Petromyzon marinus: cloning and pharmacological characterization. General and Comparative Endocrinology, 222, 106-115
Open this publication in new window or tab >>Neuropeptide Y family receptors Y1 and Y2 from sea lamprey, Petromyzon marinus: cloning and pharmacological characterization
2015 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 222, p. 106-115Article in journal (Other academic) Published
Abstract [en]

The vertebrate gene family for neuropeptide Y (NPY) receptors expanded by duplication of the chromosome carrying the ancestral Y1–Y2–Y5 gene triplet. After loss of some duplicates, the ancestral jawed vertebrate had seven receptor subtypes forming the Y1 (including Y1, Y4, Y6, Y8), Y2 (including Y2, Y7) and Y5 (only Y5) subfamilies. Lampreys are considered to have experienced the same chromosome duplications as gnathostomes and should also be expected to have multiple receptor genes. However, previously only a Y4-like and a Y5 receptor have been cloned and characterized. Here we report the cloning and characterization of two additional receptors from the sea lamprey Petromyzon marinus. Sequence phylogeny alone could not with certainty assign their identity, but based on synteny comparisons of P. marinus and the Arctic lamprey, Lethenteron camtschaticum, with jawed vertebrates, the two receptors most likely are Y1 and Y2. Both receptors were expressed in human HEK293 cells and inositol phosphate assays were performed to determine the response to the three native lamprey peptides NPY, PYY and PMY. The three peptides have similar potencies in the nanomolar range for Y1. No obvious response to the three peptides was detected for Y2. Synteny analysis supports identification of the previously cloned receptor as Y4. No additional NPY receptor genes could be identified in the presently available lamprey genome assemblies. Thus, four NPY-family receptors have been identified in lampreys, orthologs of the same subtypes as in humans (Y1, Y2, Y4 and Y5), whereas many other vertebrate lineages have retained additional ancestral subtypes.

National Category
Evolutionary Biology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-233437 (URN)10.1016/j.ygcen.2015.08.005 (DOI)000366438000012 ()26255155 (PubMedID)
Funder
Swedish Research Council
Available from: 2014-10-06 Created: 2014-10-05 Last updated: 2019-01-03Bibliographically approved
Delhomme, N., Sundström, G., Zamani, N., Lantz, H., Lin, Y. C., Hvidsten, T. R., . . . Street, N. R. (2015). Serendipitous Meta-Transcriptomics: The Fungal Community of Norway Spruce (Picea abies). PLoS ONE, 10(9), Article ID e0139080.
Open this publication in new window or tab >>Serendipitous Meta-Transcriptomics: The Fungal Community of Norway Spruce (Picea abies)
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0139080Article in journal (Refereed) Published
Abstract [en]

After performing de novo transcript assembly of >1 billion RNA-Sequencing reads obtained from 22 samples of different Norway spruce (Picea abies) tissues that were not surface sterilized, we found that assembled sequences captured a mix of plant, lichen, and fungal transcripts. The latter were likely expressed by endophytic and epiphytic symbionts, indicating that these organisms were present, alive, and metabolically active. Here, we show that these serendipitously sequenced transcripts need not be considered merely as contamination, as is common, but that they provide insight into the plant's phyllosphere. Notably, we could classify these transcripts as originating predominantly from Dothideomycetes and Leotiomycetes species, with functional annotation of gene families indicating active growth and metabolism, with particular regards to glucose intake and processing, as well as gene regulation.

National Category
Agricultural Science, Forestry and Fisheries Natural Sciences
Identifiers
urn:nbn:se:uu:diva-263259 (URN)10.1371/journal.pone.0139080 (DOI)000362170700039 ()26413905 (PubMedID)1932-6203 (Electronic) 1932-6203 (Linking) (ISBN)
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilVINNOVASwedish Research Council FormasSwedish Foundation for Strategic Research
Available from: 2015-09-29 Created: 2015-09-29 Last updated: 2017-12-01Bibliographically approved
Sundström, G., Zamani, N., Grabherr, M. G. & Mauceli, E. (2015). Whiteboard: a framework for the programmatic visualization of complex biological analyses. Bioinformatics, 31(12), 2054-2055
Open this publication in new window or tab >>Whiteboard: a framework for the programmatic visualization of complex biological analyses
2015 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 31, no 12, p. 2054-2055Article in journal (Refereed) Published
Abstract [en]

A Summary: Whiteboard is a class library implemented in C++ that enables visualization to be tightly coupled with computation when analyzing large and complex datasets.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-258774 (URN)10.1093/bioinformatics/btv078 (DOI)000356625700071 ()25661541 (PubMedID)
Available from: 2015-07-20 Created: 2015-07-20 Last updated: 2017-12-04Bibliographically approved
Zamani, N., Sundström, G., Meadows, J. R. S., Höppner, M. P., Dainat, J., Lantz, H., . . . Grabherr, M. G. (2014). A universal genomic coordinate translator for comparative genomics. BMC Bioinformatics, 15, 227
Open this publication in new window or tab >>A universal genomic coordinate translator for comparative genomics
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2014 (English)In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 15, p. 227-Article in journal (Refereed) Published
Abstract [en]

Background: Genomic duplications constitute major events in the evolution of species, allowing paralogous copies of genes to take on fine-tuned biological roles. Unambiguously identifying the orthology relationship between copies across multiple genomes can be resolved by synteny, i.e. the conserved order of genomic sequences. However, a comprehensive analysis of duplication events and their contributions to evolution would require all-to-all genome alignments, which increases at N-2 with the number of available genomes, N. Results: Here, we introduce Kraken, software that omits the all-to-all requirement by recursively traversing a graph of pairwise alignments and dynamically re-computing orthology. Kraken scales linearly with the number of targeted genomes, N, which allows for including large numbers of genomes in analyses. We first evaluated the method on the set of 12 Drosophila genomes, finding that orthologous correspondence computed indirectly through a graph of multiple synteny maps comes at minimal cost in terms of sensitivity, but reduces overall computational runtime by an order of magnitude. We then used the method on three well-annotated mammalian genomes, human, mouse, and rat, and show that up to 93% of protein coding transcripts have unambiguous pairwise orthologous relationships across the genomes. On a nucleotide level, 70 to 83% of exons match exactly at both splice junctions, and up to 97% on at least one junction. We last applied Kraken to an RNA-sequencing dataset from multiple vertebrates and diverse tissues, where we confirmed that brain-specific gene family members, i.e. one-to-many or many-to-many homologs, are more highly correlated across species than single-copy (i.e. one-to-one homologous) genes. Not limited to protein coding genes, Kraken also identifies thousands of newly identified transcribed loci, likely non-coding RNAs that are consistently transcribed in human, chimpanzee and gorilla, and maintain significant correlation of expression levels across species. Conclusions: Kraken is a computational genome coordinate translator that facilitates cross-species comparisons, distinguishes orthologs from paralogs, and does not require costly all-to-all whole genome mappings. Kraken is freely available under LPGL from http://github.com/nedaz/kraken.

Keywords
Comparative genomics, Genomic coordinate translation, Genomic duplication, Cross-species gene expression analysis
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Bioinformatics (Computational Biology) Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-229443 (URN)10.1186/1471-2105-15-227 (DOI)000338579100001 ()
Available from: 2014-08-08 Created: 2014-08-07 Last updated: 2018-01-11Bibliographically approved
Höppner, M. P., Lundquist, A., Pirun, M., Meadows, J. R. S., Zamani, N., Johnson, J., . . . Grabherr, M. G. (2014). An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes and Non-Coding Transcripts. PLoS ONE, 9(3), e91172
Open this publication in new window or tab >>An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes and Non-Coding Transcripts
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3, p. e91172-Article in journal (Refereed) Published
Abstract [en]

The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog similar to 175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional similar to 3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to,20,700 high-confidence protein coding loci, we found,4,600 antisense transcripts overlapping exons of protein coding genes, similar to 7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and,11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-223529 (URN)10.1371/journal.pone.0091172 (DOI)000332851300061 ()
Available from: 2014-04-30 Created: 2014-04-22 Last updated: 2017-12-05Bibliographically approved
Larhammar, D., Sundström, G. & Dores, R. M. (2013). Evolution of the opioid system. (2nded.). In: A. J. Kastin (Ed.), Handbook of Biologically Active Peptides: (pp. 1562-1569). Academic Press
Open this publication in new window or tab >>Evolution of the opioid system.
2013 (English)In: Handbook of Biologically Active Peptides / [ed] A. J. Kastin, Academic Press, 2013, 2nd, p. 1562-1569Chapter in book (Refereed)
Place, publisher, year, edition, pages
Academic Press, 2013 Edition: 2nd
National Category
Natural Sciences
Research subject
Biology
Identifiers
urn:nbn:se:uu:diva-205600 (URN)978-0-12-385095-9 (ISBN)
Available from: 2013-08-20 Created: 2013-08-20 Last updated: 2019-01-03Bibliographically approved
Sundström, G., Larsson, T. A., Xu, B., Heldin, J. & Larhammar, D. (2013). Interactions of zebrafish peptide YYb with the neuropeptide Y-family receptors Y4, Y7, Y8a, and Y8b. Frontiers in Neuroscience, 7, Article ID 29.
Open this publication in new window or tab >>Interactions of zebrafish peptide YYb with the neuropeptide Y-family receptors Y4, Y7, Y8a, and Y8b
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2013 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 7, article id 29Article in journal (Refereed) Published
Abstract [en]

The neuropeptide Y (NPY) system influences numerous physiological functions including feeding behavior, endocrine regulation, and cardiovascular regulation. In jawed vertebrates it consists of 3-4 peptides and 4-7 receptors. Teleost fishes have unique duplicates of NPY and PYY as well as the Y8 receptor. In the zebrafish, the NPY system consists of the peptides NPYa, PYYa, and PYYb (NPYb appears to have been lost) and at least seven NPY receptors: Y1, Y2, Y2-2, Y4, Y7, Y8a, and Y8b. Previously PYYb binding has been reported for Y2 and Y2-2. To search for peptide-receptor preferences, we have investigated PYYb binding to four of the remaining receptors and compared with NPYa and PYYa. Taken together, the most striking observations are that PYYa displays reduced affinity for Y2 (3 nM) compared to the other peptides and receptors and that all three peptides have higher affinity for Y4 (0.028-0.034 nM) than for the other five receptors. The strongest peptide preference by any receptor selectivity is the one previously reported for PYYb by the Y2 receptor, as compared to NPY and PYYa. These affinity differences may be helpful to elucidate specific details of peptide-receptor interactions. Also, we have investigated the level of mRNA expression in different organs using qPCR. All peptides and receptors have higher expression in heart, kidney, and brain. These quantitative aspects on receptor affinities and mRNA distribution help provide a more complete picture of the NPY system.

Keywords
Evolution, genome duplication, NPY, elephant shark
National Category
Natural Sciences Neurology
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-205599 (URN)10.3389/fnins.2013.00029 (DOI)000346567300029 ()23508731 (PubMedID)
Funder
Swedish Research Council
Available from: 2013-08-20 Created: 2013-08-20 Last updated: 2019-01-03Bibliographically approved
Lagman, D., Daza, D. O., Widmark, J., Abalo, X. M., Sundström, G. & Larhammar, D. (2013). The vertebrate ancestral repertoire of visual opsins, transducin alpha subunits and oxytocin/vasopressin receptors was established by duplication of their shared genomic region in the two rounds of early vertebrate genome duplications. BMC Evolutionary Biology, 13, 238
Open this publication in new window or tab >>The vertebrate ancestral repertoire of visual opsins, transducin alpha subunits and oxytocin/vasopressin receptors was established by duplication of their shared genomic region in the two rounds of early vertebrate genome duplications
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2013 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 13, p. 238-Article in journal (Refereed) Published
Abstract [en]

Background: Vertebrate color vision is dependent on four major color opsin subtypes: RH2 (green opsin), SWS1 (ultraviolet opsin), SWS2 (blue opsin), and LWS (red opsin). Together with the dim-light receptor rhodopsin (RH1), these form the family of vertebrate visual opsins. Vertebrate genomes contain many multi-membered gene families that can largely be explained by the two rounds of whole genome duplication (WGD) in the vertebrate ancestor (2R) followed by a third round in the teleost ancestor (3R). Related chromosome regions resulting from WGD or block duplications are said to form a paralogon. We describe here a paralogon containing the genes for visual opsins, the G-protein alpha subunit families for transducin (GNAT) and adenylyl cyclase inhibition (GNAI), the oxytocin and vasopressin receptors (OT/VP-R), and the L-type voltage-gated calcium channels (CACNA1-L). Results: Sequence-based phylogenies and analyses of conserved synteny show that the above-mentioned gene families, and many neighboring gene families, expanded in the early vertebrate WGDs. This allows us to deduce the following evolutionary scenario: The vertebrate ancestor had a chromosome containing the genes for two visual opsins, one GNAT, one GNAI, two OT/VP-Rs and one CACNA1-L gene. This chromosome was quadrupled in 2R. Subsequent gene losses resulted in a set of five visual opsin genes, three GNAT and GNAI genes, six OT/VP-R genes and four CACNA1-L genes. These regions were duplicated again in 3R resulting in additional teleost genes for some of the families. Major chromosomal rearrangements have taken place in the teleost genomes. By comparison with the corresponding chromosomal regions in the spotted gar, which diverged prior to 3R, we could time these rearrangements to post-3R. Conclusions: We present an extensive analysis of the paralogon housing the visual opsin, GNAT and GNAI, OT/VP-R, and CACNA1-L gene families. The combined data imply that the early vertebrate WGD events contributed to the evolution of vision and the other neuronal and neuroendocrine functions exerted by the proteins encoded by these gene families. In pouched lamprey all five visual opsin genes have previously been identified, suggesting that lampreys diverged from the jawed vertebrates after 2R.

Keywords
Visual opsins, Whole genome duplications, Chromosome rearrangements, Opsin evolution, Oxytocin receptors, Vasopressin receptors, G-protein alpha transducing subunits, Voltage-gated calcium channels
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-215296 (URN)10.1186/1471-2148-13-238 (DOI)000328459400001 ()
Note

De två (2) första författarna delar förstaförfattarskapet.

Available from: 2014-01-13 Created: 2014-01-13 Last updated: 2019-01-03Bibliographically approved
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