uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 18) Show all publications
Wang, J., Ding, J., Tan, B., Robinson, K. M., Michelson, I. H., Johansson, A., . . . Ingvarsson, P. K. (2018). A major locus controls local adaptation and adaptive life history variation in a perennial plant. Genome Biology, 19, Article ID 72.
Open this publication in new window or tab >>A major locus controls local adaptation and adaptive life history variation in a perennial plant
Show others...
2018 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 19, article id 72Article in journal (Refereed) Published
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-357691 (URN)10.1186/s13059-018-1444-y (DOI)000434210500001 ()29866176 (PubMedID)
Available from: 2018-06-04 Created: 2018-08-22 Last updated: 2018-08-25Bibliographically approved
Lin, Y.-C., Wang, J., Delhomme, N., Schiffthaler, B., Sundström, G., Zuccolo, A., . . . Street, N. R. (2018). Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen. Proceedings of the National Academy of Sciences of the United States of America, 115(46), E10970-E10978
Open this publication in new window or tab >>Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen
Show others...
2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 46, p. E10970-E10978Article in journal (Refereed) Published
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:uu:diva-366971 (URN)10.1073/pnas.1801437115 (DOI)000449934400020 ()30373829 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Foundation for Strategic Research Swedish Research CouncilEU, FP7, Seventh Framework Programme, 322739-DOUBLEUP
Available from: 2018-11-13 Created: 2018-11-27 Last updated: 2019-06-26Bibliographically approved
Zhu, Y., Engstrom, P. G., Tellgren-Roth, C., Baudo, C. D., Kennell, J. C., Sun, S., . . . Lehtio, J. (2017). Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis. Nucleic Acids Research, 45(5), 2629-2643
Open this publication in new window or tab >>Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis
Show others...
2017 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 45, no 5, p. 2629-2643Article in journal (Refereed) Published
Abstract [en]

Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene an-notation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodi-alis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-320210 (URN)10.1093/nar/gkx006 (DOI)000397286600039 ()28100699 (PubMedID)
Funder
Swedish Research Council, 2015-04622Swedish Foundation for Strategic Research The Karolinska Institutet's Research FoundationNIH (National Institute of Health), AI50113-12 AI39115-19Knut and Alice Wallenberg FoundationCancer and Allergy Foundation
Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2017-11-29Bibliographically approved
Ameur, A., Dahlberg, J., Olason, P., Vezzi, F., Karlsson, R., Martin, M., . . . Gyllensten, U. B. (2017). SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population. European Journal of Human Genetics, 25(11), 1253-1260
Open this publication in new window or tab >>SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population
Show others...
2017 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 25, no 11, p. 1253-1260Article in journal (Refereed) Published
Abstract [en]

Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-337314 (URN)10.1038/ejhg.2017.130 (DOI)000412823800012 ()28832569 (PubMedID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation, 2014.0272Swedish Research CouncilSwedish National Infrastructure for Computing (SNIC), sens2016003EU, European Research Council, 282330
Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-08-27Bibliographically approved
Reischauer, S., Stone, O. A., Villasenor, A., Chi, N., Jin, S.-W., Martin, M., . . . Stainier, D. Y. R. (2016). Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification. Nature, 535(7611), 294-+
Open this publication in new window or tab >>Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification
Show others...
2016 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 535, no 7611, p. 294-+Article in journal (Refereed) Published
Abstract [en]

Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells(1-4) and a significant increase in cardiomyocyte numbers(5). Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation(1-7) and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro.

National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-300451 (URN)10.1038/nature18614 (DOI)000379912600059 ()27411634 (PubMedID)
Funder
NIH (National Institute of Health)Ragnar Söderbergs stiftelseSwedish Research Council
Available from: 2016-08-09 Created: 2016-08-09 Last updated: 2017-11-28Bibliographically approved
Martínez Barrio, Á., Lamichhaney, S., Fan, G., Rafati, N., Pettersson, M., Zhang, H., . . . Andersson, L. (2016). The genetic basis for ecological adaptation of the Atlantic herring revealed by genome sequencing. eLIFE, 5, Article ID e12081.
Open this publication in new window or tab >>The genetic basis for ecological adaptation of the Atlantic herring revealed by genome sequencing
Show others...
2016 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 5, article id e12081Article in journal (Refereed) Published
Abstract [en]

Ecological adaptation is of major relevance to speciation and sustainable population management, but the underlying genetic factors are typically hard to study in natural populations due to genetic differentiation caused by natural selection being confounded with genetic drift in subdivided populations. Here, we use whole genome population sequencing of Atlantic and Baltic herring to reveal the underlying genetic architecture at an unprecedented detailed resolution for both adaptation to a new niche environment and timing of reproduction. We identify almost 500 independent loci associated with a recent niche expansion from marine (Atlantic Ocean) to brackish waters (Baltic Sea), and more than 100 independent loci showing genetic differentiation between spring- and autumn-spawning populations irrespective of geographic origin. Our results show that both coding and non-coding changes contribute to adaptation. Haplotype blocks, often spanning multiple genes and maintained by selection, are associated with genetic differentiation.

National Category
Genetics and Breeding Evolutionary Biology Genetics Fish and Aquacultural Science
Identifiers
urn:nbn:se:uu:diva-279967 (URN)10.7554/eLife.12081 (DOI)000387459700001 ()27138043 (PubMedID)
Funder
EU, European Research CouncilSwedish Research Council FormasKnut and Alice Wallenberg Foundation
Note

Alvaro Martinez Barrio, Sangeet Lamichhaney, Guangyi Fan and Nima Rafati contributed equally to this work.

Available from: 2016-03-06 Created: 2016-03-06 Last updated: 2017-11-29Bibliographically approved
Kutsenko, A., Svensson, T., Nystedt, B., Lundeberg, J., Bjork, P., Sonnhammer, E., . . . Wieslander, L. (2014). The Chironomus tentans genome sequence and the organization of the Balbiani ring genes. BMC Genomics, 15, 819
Open this publication in new window or tab >>The Chironomus tentans genome sequence and the organization of the Balbiani ring genes
Show others...
2014 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, p. 819-Article in journal (Refereed) Published
Abstract [en]

Background: The polytene nuclei of the dipteran Chironomus tentans (Ch. tentans) with their Balbiani ring (BR) genes constitute an exceptional model system for studies of the expression of endogenous eukaryotic genes. Here, we report the first draft genome of Ch. tentans and characterize its gene expression machineries and genomic architecture of the BR genes. Results: The genome of Ch. tentans is approximately 200 Mb in size, and has a low GC content (31%) and a low repeat fraction (15%) compared to other Dipteran species. Phylogenetic inference revealed that Ch. tentans is a sister clade to mosquitoes, with a split 150-250 million years ago. To characterize the Ch. tentans gene expression machineries, we identified potential orthologus sequences to more than 600 Drosophila melanogaster (D. melanogaster) proteins involved in the expression of protein-coding genes. We report novel data on the organization of the BR gene loci, including a novel putative BR gene, and we present a model for the organization of chromatin bundles in the BR2 puff based on genic and intergenic in situ hybridizations. Conclusions: We show that the molecular machineries operating in gene expression are largely conserved between Ch. tentans and D. melanogaster, and we provide enhanced insight into the organization and expression of the BR genes. Our data strengthen the generality of the BR genes as a unique model system and provide essential background for in-depth studies of the biogenesis of messenger ribonucleoprotein complexes.

Keywords
Eukaryotic gene expression, Model organisms, Balbiani ring genes, Chromosome puffs
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-235629 (URN)10.1186/1471-2164-15-819 (DOI)000342590400001 ()
Available from: 2014-11-11 Created: 2014-11-06 Last updated: 2017-12-05Bibliographically approved
Guy, L., Nystedt, B., Toft, C., Zaremba-Niedzwiedzka, K., Berglund, E. C., Granberg, F., . . . Andersson, S. G. E. (2013). A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen Bartonella. PLOS Genetics, 9(3), e1003393
Open this publication in new window or tab >>A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen Bartonella
Show others...
2013 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 3, p. e1003393-Article in journal (Refereed) Published
Abstract [en]

Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a catadapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-199485 (URN)10.1371/journal.pgen.1003393 (DOI)000316866700064 ()
Available from: 2013-05-07 Created: 2013-05-06 Last updated: 2017-12-06Bibliographically approved
Nystedt, B. (2009). Evolutionary Processes and Genome Dynamics in Host-Adapted Bacteria. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Evolutionary Processes and Genome Dynamics in Host-Adapted Bacteria
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Many bacteria live in close association with other organisms such as plants and animals, with important implications for both health and disease. This thesis investigates bacteria that are well adapted to live inside an animal host, and describes the molecular evolutionary processes underlying host-adaptation, based on bacterial genome comparisons.

Insect-transmitted bacteria of the genus Bartonella infect the red blood cells of mammals, and we investigate host adaptation and genome evolution in this genus. In Bartonella, many host-interaction systems are encoded in a highly variable chromosomal segment previously shown to be amplified and packaged into bacteriophage particles. Among all genes imported into the Bartonella ancestor, we identify the short gene cluster encoding these phage particles as the most evolutionary conserved, indicating a strong selective advantage and a role in niche adaptation. We also provide an overview of the remarkable evolutionary dynamics of type IV and type V secretion systems, including a detailed analysis of the type IV secretion system trw. Our results highlight the importance of recombination and gene conversion in the evolution of host-adaptation systems, and reveal how these mutational mechanisms result in strikingly different outcomes depending on the selective constraints.

In the insect endosymbionts Buchnera and Blochmannia, we show that genes frameshifted at poly(A) tracts can remain functional due to transcriptional slippage. Selection against poly(A) tracts is very inefficient in these genomes compared to other bacteria, and we discuss why this can lead to increased rates of gene loss. Using the human pathogen Helicobacter pylori as a model, we provide a deeper understanding of why highly expressed genes evolve slowly.

This thesis emphasizes the power of using complete genome sequences to study evolutionary processes. In particular, we argue that knowledge about the complex evolution of duplicated gene segments is crucial to understand host adaptation in bacteria.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. p. 64
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 668
Keywords
molecular evolution, pathogen, secretion system, Bartonella, Buchnera, Blochmannia, Helicobacter
National Category
Bioinformatics and Systems Biology
Research subject
Evolutionary Genetics
Identifiers
urn:nbn:se:uu:diva-107720 (URN)978-91-554-7596-3 (ISBN)
Public defence
2009-10-09, Lindahlsalen, EBC, Norbyvägen 18, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-09-18 Created: 2009-08-24 Last updated: 2009-09-22
Nystedt, B., Frank, C., Thollesson, M. & Andersson, S. (2008). Diversifying Selection and Concerted Evolution of a Type IV Secretion System in Bartonella. Molecular biology and evolution, 25(2), 287-300
Open this publication in new window or tab >>Diversifying Selection and Concerted Evolution of a Type IV Secretion System in Bartonella
2008 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 25, no 2, p. 287-300Article in journal (Refereed) Published
Abstract [en]

We have studied the evolution of a type TV secretion system (T4SS), in Bartonella, which is thought to have changed function from conjugation to erythrocyte adherence following a recent horizontal gene transfer event. The system, called Trw, is unique among T4SSs in that genes encoding both exo- and intracellular components are located within the same duplicated fragment. This provides an opportunity to study the influence of selection on proteins involved in host-pathogen interactions. We sequenced the trw locus from several strains of Bartonella henselae and investigated its evolutionary history by comparisons to other Bartonella species. Several instances of recombination and gene conversion events where detected in the 2- to 5-fold duplicated gene fragments encompassing trwJIH, explaining the homogenization of the anchoring protein TrwI and the divergence of the minor pilus protein TrwJ. A phylogenetic analysis of the 7- to 8-fold duplicated gene coding for the major pilus protein TrwL displayed 2 distinct clades, likely representing a subfunctionalization event. The analyses of the B. henselae strains also identified a recent horizontal transfer event of almost the complete trwL region. We suggest that the switch in function of the T4SS was mediated by the duplication of the genes encoding pilus components and their diversification by combinatorial sequence shuffling within and among genomes. We suggest that the pilus proteins have evolved by diversifying selection to match a divergent set of erythrocyte surface structures, consistent with the trench warfare coevolutionary model.

Keywords
type IV secretion system, Bartonella, duplication, recombination, gene conversion, host-pathogen interaction
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-14988 (URN)10.1093/molbev/msm252 (DOI)000253634800007 ()18065487 (PubMedID)
Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2017-12-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-7809-7664

Search in DiVA

Show all publications