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13 Publications visible to you, out of a total of 13
SALARECON connects the Atlantic salmon genome to growth and feed efficiency

Abstract (Expand)

Atlantic salmon (Salmo salar) is the most valuable farmed fish globally and there is much interest in optimizing its genetics and rearing conditions for growth and feed efficiency. Marine feed ingredients … must be replaced to meet global demand, with challenges for fish health and sustainability. Metabolic models can address this by connecting genomes to metabolism, which converts nutrients in the feed to energy and biomass, but such models are currently not available for major aquaculture species such as salmon. We present SALARECON, a model focusing on energy, amino acid, and nucleotide metabolism that links the Atlantic salmon genome to metabolic fluxes and growth. It performs well in standardized tests and captures expected metabolic (in)capabilities. We show that it can explain observed hypoxic growth in terms of metabolic fluxes and apply it to aquaculture by simulating growth with commercial feed ingredients. Predicted limiting amino acids and feed efficiencies agree with data, and the model suggests that marine feed efficiency can be achieved by supplementing a few amino acids to plant- and insect-based feeds. SALARECON is a high-quality model that makes it possible to simulate Atlantic salmon metabolism and growth. It can be used to explain Atlantic salmon physiology and address key challenges in aquaculture such as development of sustainable feeds.

Authors: Maksim Zakhartsev, Filip Rotnes, Marie Gulla, Ove Oyas, Jesse van Dam, Maria Suarez Diez, Fabian Grammes, Robert Hafthorsson, Wout van Helvoirt, Jasper Koehorst, Peter Schaap, Yang Jin, Liv Torunn Mydland, Arne Gjuvsland, Sandve Simen, Vitor Martins dos Santos, Jon Olav Vik

Date Published: 1st Jun 2022

Publication Type: Journal

CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes

Abstract (Expand)

Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long … chain fatty acyl elongases (Elovls) and fatty acyl desaturases (Fads), albeit to a limited degree. Understanding molecular mechanisms of PUFA biosynthesis and regulation is a pre-requisite for sustainable use of vegetable oils in aquafeeds as current sources of fish oils are unable to meet increasing demands for omega-3 PUFAs. By generating CRISPR-mediated elovl2 partial knockout (KO), we have shown that elovl2 is crucial for multi-tissue synthesis of 22:6n-3 in vivo and that endogenously synthesized PUFAs are important for transcriptional regulation of lipogenic genes in Atlantic salmon. The elovl2-KOs showed reduced levels of 22:6n-3 and accumulation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the liver, brain and white muscle, suggesting inhibition of elongation. Additionally, elovl2-KO salmon showed accumulation of 20:4n-6 in brain and white muscle. The impaired synthesis of 22:6n-3 induced hepatic expression of sterol regulatory element binding protein-1 (srebp-1), fatty acid synthase-b, Δ6fad-a, Δ5fad and elovl5. Our study demonstrates key roles of elovl2 at two penultimate steps of PUFA synthesis in vivo and suggests Srebp-1 as a main regulator of endogenous PUFA synthesis in Atlantic salmon.

Authors: Alex K. Datsomor, Nikola Zic, Keshuai Li, Rolf E. Olsen, Yang Jin, Jon Olav Vik, Rolf B. Edvardsen, Fabian Grammes, Anna Wargelius, Per Winge

Date Published: 1st Dec 2019

Publication Type: Not specified

Predicting Metabolism from Gene Expression in an Improved Whole-Genome Metabolic Network Model of Danio rerio.

Abstract (Expand)

Zebrafish is a useful modeling organism for the study of vertebrate development, immune response, and metabolism. Metabolic studies can be aided by mathematical reconstructions of the metabolic network … of zebrafish. These list the substrates and products of all biochemical reactions that occur in the zebrafish. Mathematical techniques such as flux-balance analysis then make it possible to predict the possible metabolic flux distributions that optimize, for example, the turnover of food into biomass. The only available genome-scale reconstruction of zebrafish metabolism is ZebraGEM. In this study, we present ZebraGEM 2.0, an updated and validated version of ZebraGEM. ZebraGEM 2.0 is extended with gene-protein-reaction associations (GPRs) that are required to integrate genetic data with the metabolic model. To demonstrate the use of these GPRs, we performed an in silico genetic screening for knockouts of metabolic genes and validated the results against published in vivo genetic knockout and knockdown screenings. Among the single knockout simulations, we identified 74 essential genes, whose knockout stopped growth completely. Among these, 11 genes are known have an abnormal knockout or knockdown phenotype in vivo (partial), and 41 have human homologs associated with metabolic diseases. We also added the oxidative phosphorylation pathway, which was unavailable in the published version of ZebraGEM. The updated model performs better than the original model on a predetermined list of metabolic functions. We also determined a minimal feed composition. The oxidative phosphorylation pathways were validated by comparing with published experiments in which key components of the oxidative phosphorylation pathway were pharmacologically inhibited. To test the utility of ZebraGEM2.0 for obtaining new results, we integrated gene expression data from control and Mycobacterium marinum-infected zebrafish larvae. The resulting model predicts impeded growth and altered histidine metabolism in the infected larvae.

Authors: L. van Steijn, F. J. Verbeek, H. P. Spaink, R. M. H. Merks

Date Published: 20th Jun 2019

Publication Type: Not specified

Rainbow Trout (Oncorhynchus Mykiss) Intestinal Epithelial Cells as a Model for Studying Gut Immune Function and Effects of Functional Feed Ingredients

Abstract (Expand)

The objective of this study was to evaluate the suitability of the rainbow trout intestinal epithelial cell line (RTgutGC) as an in vitro model for studies of gut immune function and effects of functional … feed ingredients. Effects of lipopolysaccharide (LPS) and three functional feed ingredients [nucleotides, mannanoligosaccharides (MOS), and beta-glucans] were evaluated in RTgutGC cells grown on conventional culture plates and transwell membranes. Permeation of fluorescently-labeled albumin, transepithelial electrical resistance (TEER), and tight junction protein expression confirmed the barrier function of the cells. Brush border membrane enzyme activities [leucine aminopeptidase (LAP) and maltase] were detected in the RTgutGC cells but activity levels were not modulated by any of the exposures. Immune related genes were expressed at comparable relative basal levels as these in rainbow trout distal intestine. LPS produced markedly elevated gene expression levels of the pro-inflammatory cytokines il1b, il6, il8, and tnfa but had no effect on ROS production. Immunostaining demonstrated increased F-actin contents after LPS exposure. Among the functional feed ingredients, MOS seemed to be the most potent modulator of RTgutGC immune and barrier function. MOS significantly increased albumin permeation and il1b, il6, il8, tnfa, and tgfb expression, but suppressed ROS production, cell proliferation and myd88 expression. Induced levels of il1b and il8 were also observed after treatment with nucleotides and beta-glucans. For barrier function related genes, all treatments up-regulated the expression of cldn3 and suppressed cdh1 levels. Beta-glucans increased TEER levels and F-actin content. Collectively, the present study has provided new information on how functional ingredients commonly applied in aquafeeds can affect intestinal epithelial function in fish. Our findings suggest that RTgutGC cells possess characteristic features of functional intestinal epithelial cells indicating a potential for use as an efficient in vitro model to evaluate effects of bioactive feed ingredients on gut immune and barrier functions and their underlying cellular mechanisms.

Authors: Jie Wang, Peng Lei, Amr Ahmed Abdelrahim Gamil, Leidy Lagos, Yang Yue, Kristin Schirmer, Liv Torunn Mydland, Margareth Overland, Åshild Krogdahl, Trond M. Kortner

Date Published: 6th Feb 2019

Publication Type: Journal

Atlantic salmon raised with diets low in long-chain polyunsaturated n-3 fatty acids in freshwater have a Mycoplasma-dominated gut microbiota at sea

Abstract (Expand)

Factors affecting the establishment of the gut microbiota in animals living in marine environments remain largely unknown. In terrestrial animals, however, it is well established that the juvenile … environment has a major impact on the gut microbiota later in life. Atlantic salmon Salmo salar is an anadromous fish important in aquaculture with a juvenile freshwater stage and an adult seawater stage. For wild salmon, there are major dietary changes with respect to availability of long-chain polyunsaturated n-3 fatty acids (LC-n-3 PUFA) with lower abundance in freshwater systems. The aim of our work was therefore to determine the effect of a juvenile freshwater diet with high LC-n-3 PUFA, as compared to a diet low in LC-n-3 PUFA (designed to increase the endogenous LC-n-3 PUFA production), on the transition to a seawater gut microbiota for Atlantic salmon. We found a juvenile freshwater microbiota high in Firmicutes for fish raised with low LC-n-3 PUFA, while the microbiota for fish given high LC-n-3 PUFA feed was high in Proteobacteria. One hundred days after transfer to a common sea cage, fish that were given low LC-n-3 PUFA diets in freshwater showed significantly higher (p = 0.02, Kruskal-Wallis) Mycoplasma content (90 ± 7%; mean ± SD) compared to fish raised on a high LC-n-3 PUFA diet in freshwater (25 ± 31% Mycoplasma). Shotgun metagenome sequencing from fish raised with a low LC-n-3 PUFA diet identified a salmon-associated Mycoplasma in sea, being distinct from currently known Mycoplasma. The genome sequence information indicated a mutualistic lifestyle of this bacterium. Mycoplasma has also previously been identified as dominant (>70%) in sea-living adult Atlantic salmon. Taken together, our results suggest that the juvenile freshwater diet influences the establishment of the gut microbiota in marine Atlantic salmon.

Authors: Y Jin, IL Angell, SR Sandve, LG Snipen, Y Olsen, K Rudi

Date Published: 24th Jan 2019

Publication Type: Not specified

Stable Core Gut Microbiota across the Freshwater-to-Saltwater Transition for Farmed Atlantic Salmon

Abstract (Expand)

Gut microbiota associations through habitat transitions are fundamentally important yet poorly understood. One such habitat transition is the migration from freshwater to saltwater for anadromous fish, … such as salmon. The aim of the current work was therefore to determine the freshwater-to-saltwater transition impact on the gut microbiota in farmed Atlantic salmon, with dietary interventions resembling freshwater and saltwater diets with respect to fatty acid composition. Using deep 16S rRNA gene sequencing and quantitative PCR, we found that the freshwater-to-saltwater transition had a major association with the microbiota composition and quantity, while diet did not show significant associations with the microbiota. In saltwater there was a 100-fold increase in bacterial quantity, with a relative increase of Firmicutes and a relative decrease of both Actinobacteria and Proteobacteria. Irrespective of an overall shift in microbiota composition from freshwater to saltwater, we identified three core clostridia and one Lactobacillus-affiliated phylotype with wide geographic distribution that were highly prevalent and co-occurring. Taken together, our results support the importance of the dominating bacteria in the salmon gut, with the freshwater microbiota being immature. Due to the low number of potentially host-associated bacterial species in the salmon gut, we believe that farmed salmon can represent an important model for future understanding of host-bacterium interactions in aquatic environments. IMPORTANCE Little is known about factors affecting the interindividual distribution of gut bacteria in aquatic environments. We have shown that there is a core of four highly prevalent and co-occurring bacteria irrespective of feed and freshwater-to-saltwater transition. The potential host interactions of the core bacteria, however, need to be elucidated further.

Authors: Knut Rudi, Inga Leena Angell, Phillip B. Pope, Jon Olav Vik, Simen Rød Sandve, Lars-Gustav Snipen

Date Published: 15th Jan 2018

Publication Type: Not specified

The Atlantic salmon genome provides insights into rediploidization

Abstract (Expand)

The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about … the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

Authors: S. Lien, B. F. Koop, S. R. Sandve, J. R. Miller, M. P. Kent, T. Nome, T. R. Hvidsten, J. S. Leong, D. R. Minkley, A. Zimin, F. Grammes, H. Grove, A. Gjuvsland, B. Walenz, R. A. Hermansen, K. von Schalburg, E. B. Rondeau, A. Di Genova, J. K. Samy, J. Olav Vik, M. D. Vigeland, L. Caler, U. Grimholt, S. Jentoft, D. Inge Vage, P. de Jong, T. Moen, M. Baranski, Y. Palti, D. R. Smith, J. A. Yorke, A. J. Nederbragt, A. Tooming-Klunderud, K. S. Jakobsen, X. Jiang, D. Fan, Y. Hu, D. A. Liberles, R. Vidal, P. Iturra, S. J. Jones, I. Jonassen, A. Maass, S. W. Omholt, W. S. Davidson

Date Published: 18th Apr 2016

Publication Type: Not specified

UPARSE: highly accurate OTU sequences from microbial amplicon reads

Abstract (Expand)

Amplified marker-gene sequences can be used to understand microbial community structure, but they suffer from a high level of sequencing and amplification artifacts. The UPARSE pipeline reports operational … taxonomic unit (OTU) sequences with </=1% incorrect bases in artificial microbial community tests, compared with >3% incorrect bases commonly reported by other methods. The improved accuracy results in far fewer OTUs, consistently closer to the expected number of species in a community.

Author: R. C. Edgar

Date Published: 18th Aug 2013

Publication Type: Not specified

Reconstruction of Danio rerio metabolic model accounting for subcellular compartmentalisation

Abstract (Expand)

Plant and microbial metabolic engineering is commonly used in the production of functional foods and quality trait improvement. Computational model-based approaches have been used in this important … endeavour. However, to date, fish metabolic models have only been scarcely and partially developed, in marked contrast to their prominent success in metabolic engineering. In this study we present the reconstruction of fully compartmentalised models of the Danio rerio (zebrafish) on a global scale. This reconstruction involves extraction of known biochemical reactions in D. rerio for both primary and secondary metabolism and the implementation of methods for determining subcellular localisation and assignment of enzymes. The reconstructed model (ZebraGEM) is amenable for constraint-based modelling analysis, and accounts for 4,988 genes coding for 2,406 gene-associated reactions and only 418 non-gene-associated reactions. A set of computational validations (i.e., simulations of known metabolic functionalities and experimental data) strongly testifies to the predictive ability of the model. Overall, the reconstructed model is expected to lay down the foundations for computational-based rational design of fish metabolic engineering in aquaculture.

Author: M. Bekaert

Date Published: 14th Nov 2012

Publication Type: Not specified

Search and clustering orders of magnitude faster than BLAST

Abstract (Expand)

MOTIVATION: Biological sequence data is accumulating rapidly, motivating the development of improved high-throughput methods for sequence classification. RESULTS: UBLAST and USEARCH are new algorithms … enabling sensitive local and global search of large sequence databases at exceptionally high speeds. They are often orders of magnitude faster than BLAST in practical applications, though sensitivity to distant protein relationships is lower. UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters. UCLUST offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets. AVAILABILITY: Binaries are available at no charge for non-commercial use at http://www.drive5.com/usearch.

Author: R. C. Edgar

Date Published: 12th Aug 2010

Publication Type: Not specified

QIIME allows analysis of high-throughput community sequencing data

Abstract

Not specified

Authors: J. G. Caporaso, J. Kuczynski, J. Stombaugh, K. Bittinger, F. D. Bushman, E. K. Costello, N. Fierer, A. G. Pena, J. K. Goodrich, J. I. Gordon, G. A. Huttley, S. T. Kelley, D. Knights, J. E. Koenig, R. E. Ley, C. A. Lozupone, D. McDonald, B. D. Muegge, M. Pirrung, J. Reeder, J. R. Sevinsky, P. J. Turnbaugh, W. A. Walters, J. Widmann, T. Yatsunenko, J. Zaneveld, R. Knight

Date Published: 11th Apr 2010

Publication Type: Not specified

Minimum information about a microarray experiment (MIAME)-toward standards for microarray data

Abstract (Expand)

Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation … has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.

Authors: A. Brazma, P. Hingamp, J. Quackenbush, G. Sherlock, P. Spellman, C. Stoeckert, J. Aach, W. Ansorge, C. A. Ball, H. C. Causton, T. Gaasterland, P. Glenisson, F. C. Holstege, I. F. Kim, V. Markowitz, J. C. Matese, H. Parkinson, A. Robinson, U. Sarkans, S. Schulze-Kremer, J. Stewart, R. Taylor, J. Vilo, M. Vingron

Date Published: 1st Dec 2001

Publication Type: Not specified

Life-stage associated remodeling of lipid metabolism regulation in Atlantic salmon.

Abstract (Expand)

Atlantic salmon migrates from rivers to sea to feed, grow and develop gonads before returning to spawn in freshwater. The transition to marine habitats is associated with dramatic changes in the … environment, including water salinity, exposure to pathogens, and shift in dietary lipid availability. Many changes in physiology and metabolism occur across this life-stage transition, but little is known about the molecular nature of these changes. Here we use a long term feeding experiment to study transcriptional regulation of lipid metabolism in Atlantic salmon gut and liver in both fresh- and saltwater. We find that lipid metabolism becomes significantly less plastic to differences in dietary lipid composition when salmon transitions to saltwater and experiences increased dietary lipid availability. Expression of genes in liver relating to lipogenesis and lipid transport decrease overall and become less responsive to diet, while genes for lipid uptake in gut become more highly expressed. Finally, analyses of evolutionary consequences of the salmonid specific whole-genome duplication on lipid metabolism reveals several pathways with significantly different (p<0.05) duplicate retention or duplicate regulatory conservation. We also find a limited number of cases where the whole genome duplication has resulted in an increased gene dosage. In conclusion, we find variable and pathway-specific effects of the salmonid genome duplication on lipid metabolism genes. A clear life-stage associated shift in lipid metabolism regulation is evident, and we hypothesize this to be, at least partly, driven by non-dietary factors such as the preparatory remodeling of gene regulation and physiology prior to sea migration. This article is protected by copyright. All rights reserved.

Authors: G. Gillard, T. N. Harvey, A. Gjuvsland, Y. Jin, M. Thomassen, S. Lien, M. Leaver, J. S. Torgersen, T. R. Hvidsten, J. O. Vik, S. R. Sandve

Date Published: No date defined

Publication Type: Not specified

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