Genome-Wide Reconstruction of Rediploidization Following Autopolyploidization across One Hundred Million Years of Salmonid Evolution.

The long-term evolutionary impacts of whole-genome duplication (WGD) are strongly influenced by the ensuing rediploidization process. Following autopolyploidization, rediploidization involves a transition from tetraploid to diploid meiotic pairing, allowing duplicated genes (ohnologs) to diverge genetically and functionally. Our understanding of autopolyploid rediploidization has been informed by a WGD event ancestral to salmonid fishes, where large genomic regions are characterized by temporally delayed rediploidization, allowing lineage-specific ohnolog sequence divergence in the major salmonid clades. Here, we investigate the long-term outcomes of autopolyploid rediploidization at genome-wide resolution, exploiting a recent "explosion" of salmonid genome assemblies, including a new genome sequence for the huchen (Hucho hucho). We developed a genome alignment approach to capture duplicated regions across multiple species, allowing us to create 121,864 phylogenetic trees describing genome-wide ohnolog divergence across salmonid evolution. Using molecular clock analysis, we show that 61% of the ancestral salmonid genome experienced an initial "wave" of rediploidization in the late Cretaceous (85-106 Ma). This was followed by a period of relative genomic stasis lasting 17-39 My, where much of the genome remained tetraploid. A second rediploidization wave began in the early Eocene and proceeded alongside species diversification, generating predictable patterns of lineage-specific ohnolog divergence, scaling in complexity with the number of speciation events. Using gene set enrichment, gene expression, and codon-based selection analyses, we provide insights into potential functional outcomes of delayed rediploidization. This study enhances our understanding of delayed autopolyploid rediploidization and has broad implications for future studies of WGD events.

SALARECON connects the Atlantic salmon genome to growth and feed efficiency.

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.

Diversified regulation of circadian clock gene expression following whole genome duplication.

Across taxa, circadian control of physiology and behavior arises from cell-autonomous oscillations in gene expression, governed by a networks of so-called 'clock genes', collectively forming transcription-translation feedback loops. In modern vertebrates, these networks contain multiple copies of clock gene family members, which arose through whole genome duplication (WGD) events during evolutionary history. It remains unclear to what extent multiple copies of clock gene family members are functionally redundant or have allowed for functional diversification. We addressed this problem through an analysis of clock gene expression in the Atlantic salmon, a representative of the salmonids, a group which has undergone at least 4 rounds of WGD since the base of the vertebrate lineage, giving an unusually large complement of clock genes. By comparing expression patterns across multiple tissues, and during development, we present evidence for gene- and tissue-specific divergence in expression patterns, consistent with functional diversification of clock gene duplicates. In contrast to mammals, we found no evidence for coupling between cortisol and circadian gene expression, but cortisol mediated non-circadian regulated expression of a subset of clock genes in the salmon gill was evident. This regulation is linked to changes in gill function necessary for the transition from fresh- to sea-water in anadromous fish. Overall, this analysis emphasises the potential for a richly diversified clock gene network to serve a mixture of circadian and non-circadian functions in vertebrate groups with complex genomes.

The Atlantic salmon genome provides insights into rediploidization.

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.

Evolution of Cold Acclimation and Its Role in Niche Transition in the Temperate Grass Subfamily Pooideae.

The grass subfamily Pooideae dominates the grass floras in cold temperate regions and has evolved complex physiological adaptations to cope with extreme environmental conditions like frost, winter, and seasonality. One such adaptation is cold acclimation, wherein plants increase their frost tolerance in response to gradually falling temperatures and shorter days in the autumn. However, understanding how complex traits like cold acclimation evolve remains a major challenge in evolutionary biology. Here, we investigated the evolution of cold acclimation in Pooideae and found that a phylogenetically diverse set of Pooideae species displayed cold acclimation capacity. However, comparing differential gene expression after cold treatment in transcriptomes of five phylogenetically diverse species revealed widespread species-specific responses of genes with conserved sequences. Furthermore, we studied the correlation between gene family size and number of cold-responsive genes as well as between selection pressure on coding sequences of genes and their cold responsiveness. We saw evidence of protein-coding and regulatory sequence evolution as well as the origin of novel genes and functions contributing toward evolution of a cold response in Pooideae. Our results reflect that selection pressure resulting from global cooling must have acted on already diverged lineages. Nevertheless, conservation of cold-induced gene expression of certain genes indicates that the Pooideae ancestor may have possessed some molecular machinery to mitigate cold stress. Evolution of adaptations to seasonally cold climates is regarded as particularly difficult. How Pooideae evolved to transition from tropical to temperate biomes sheds light on how complex traits evolve in the light of climate changes.

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

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 decreases overall and becomes 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 reveal several pathways with significantly different (p < .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 nondietary factors such as the preparatory remodelling of gene regulation and physiology prior to sea migration.

A systemic study of lipid metabolism regulation in salmon fingerlings and early juveniles fed plant oil.

In salmon farming, the scarcity of fish oil has driven a shift towards the use of plant-based oil from vegetable or seed, leading to fish feed low in long-chain PUFA (LC-PUFA) and cholesterol. Atlantic salmon has the capacity to synthesise both LC-PUFA and cholesterol, but little is known about the regulation of synthesis and how it varies throughout salmon life span. Here, we present a systemic view of lipid metabolism pathways based on lipid analyses and transcriptomic data from salmon fed contrasting diets of plant or fish oil from first feeding. We analysed four tissues (stomach, pyloric caeca, hindgut and liver) at three life stages (initial feeding 0·16 g, 2·5 g fingerlings and 10 g juveniles). The strongest response to diets higher in plant oil was seen in pyloric caeca of fingerlings, with up-regulation of thirty genes in pathways for cholesterol uptake, transport and biosynthesis. In juveniles, only eleven genes showed differential expression in pyloric caeca. This indicates a higher requirement of dietary cholesterol in fingerlings, which could result in a more sensitive response to plant oil. The LC-PUFA elongation and desaturation pathway was down-regulated in pyloric caeca, probably regulated by srebp1 genes. In liver, cholesterol metabolism and elongation and desaturation genes were both higher on plant oil. Stomach and hindgut were not notably affected by dietary treatment. Plant oil also had a higher impact on fatty acid composition of fingerlings compared with juveniles, suggesting that fingerlings have less metabolic regulatory control when primed with plant oil diet compared with juveniles.

Functional Annotation of All Salmonid Genomes (FAASG): an international initiative supporting future salmonid research, conservation and aquaculture.

We describe an emerging initiative - the 'Functional Annotation of All Salmonid Genomes' (FAASG), which will leverage the extensive trait diversity that has evolved since a whole genome duplication event in the salmonid ancestor, to develop an integrative understanding of the functional genomic basis of phenotypic variation. The outcomes of FAASG will have diverse applications, ranging from improved understanding of genome evolution, to improving the efficiency and sustainability of aquaculture production, supporting the future of fundamental and applied research in an iconic fish lineage of major societal importance.

Two adjacent inversions maintain genomic differentiation between migratory and stationary ecotypes of Atlantic cod.

Atlantic cod is composed of multiple migratory and stationary populations widely distributed in the North Atlantic Ocean. The Northeast Arctic cod (NEAC) population in the Barents Sea undertakes annual spawning migrations to the northern Norwegian coast. Although spawning occurs sympatrically with the stationary Norwegian coastal cod (NCC), phenotypic and genetic differences between NEAC and NCC are maintained. In this study, we resolve the enigma by revealing the mechanisms underlying these differences. Extended linkage disequilibrium (LD) and population divergence were demonstrated in a 17.4-Mb region on linkage group 1 (LG1) based on genotypes of 494 SNPs from 192 parents of farmed families of NEAC, NCC or NEACxNCC crosses. Linkage analyses revealed two adjacent inversions within this region that repress meiotic recombination in NEACxNCC crosses. We identified a NEAC-specific haplotype consisting of 186 SNPs that was fixed in NEAC sampled from the Barents Sea, but segregating under Hardy-Weinberg equilibrium in eight NCC stocks. Comparative genomic analyses determine the NEAC configuration of the inversions to be the derived state and date it to ~1.6-2.0 Mya. The haplotype block harbours 763 genes, including candidates regulating swim bladder pressure, haem synthesis and skeletal muscle organization conferring adaptation to long-distance migrations and vertical movements down to large depths. Our results suggest that the migratory ecotype experiences strong directional selection for the two adjacent inversions on LG1. Despite interbreeding between NEAC and NCC, the inversions are maintaining genetic differentiation, and we hypothesize the co-occurrence of multiple adaptive alleles forming a 'supergene' in the NEAC population.

Utilization of deletion bins to anchor and order sequences along the wheat 7B chromosome.

KEY MESSAGE: A total of 3,671 sequence contigs and scaffolds were mapped to deletion bins on wheat chromosome 7B providing a foundation for developing high-resolution integrated physical map for this chromosome. Bread wheat (Triticum aestivum L.) has a large, complex and highly repetitive genome which is challenging to assemble into high quality pseudo-chromosomes. As part of the international effort to sequence the hexaploid bread wheat genome by the international wheat genome sequencing consortium (IWGSC) we are focused on assembling a reference sequence for chromosome 7B. The successful completion of the reference chromosome sequence is highly dependent on the integration of genetic and physical maps. To aid the integration of these two types of maps, we have constructed a high-density deletion bin map of chromosome 7B. Using the 270 K Nimblegen comparative genomic hybridization (CGH) array on a set of cv. Chinese spring deletion lines, a total of 3,671 sequence contigs and scaffolds (~7.8 % of chromosome 7B physical length) were mapped into nine deletion bins. Our method of genotyping deletions on chromosome 7B relied on a model-based clustering algorithm (Mclust) to accurately predict the presence or absence of a given genomic sequence in a deletion line. The bin mapping results were validated using three different approaches, viz. (a) PCR-based amplification of randomly selected bin mapped sequences (b) comparison with previously mapped ESTs and (c) comparison with a 7B genetic map developed in the present study. Validation of the bin mapping results suggested a high accuracy of the assignment of 7B sequence contigs and scaffolds to the 7B deletion bins.

The genome regulatory landscape of Atlantic salmon liver through smoltification.

The anadromous Atlantic salmon undergo a preparatory physiological transformation before seawater entry, referred to as smoltification. Key molecular developmental processes involved in this life stage transition, such as remodeling of gill functions, are known to be synchronized and modulated by environmental cues like photoperiod. However, little is known about the photoperiod influence and genome regulatory processes driving other canonical aspects of smoltification such as the large-scale changes in lipid metabolism and energy homeostasis in the developing smolt liver. Here we generate transcriptome, DNA methylation, and chromatin accessibility data from salmon livers across smoltification under different photoperiod regimes. We find a systematic reduction of expression levels of genes with a metabolic function, such as lipid metabolism, and increased expression of energy related genes such as oxidative phosphorylation, during smolt development in freshwater. However, in contrast to similar studies of the gill, smolt liver gene expression prior to seawater transfer was not impacted by photoperiodic history. Integrated analyses of gene expression, chromatin accessibility, and transcription factor (TF) binding signatures highlight chromatin remodeling and TF dynamics underlying smolt gene regulatory changes. Differential peak accessibility patterns largely matched differential gene expression patterns during smoltification and we infer that ZNF682, KLFs, and NFY TFs are important in driving a liver metabolic shift from synthesis to break down of organic compounds in freshwater. Overall, chromatin accessibility and TFBS occupancy were highly correlated to changes in gene expression. On the other hand, we identified numerous differential methylation patterns across the genome, but associated genes were not functionally enriched or correlated to observed gene expression changes across smolt development. Taken together, this work highlights the relative importance of chromatin remodeling during smoltification and demonstrates that metabolic remodeling occurs as a preadaptation to life at sea that is not to a large extent driven by photoperiod history.

Hypothalamic tanycytes as mediators of maternally programmed seasonal plasticity.

In mammals, maternal photoperiodic programming (MPP) provides a means whereby juvenile development can be matched to forthcoming seasonal environmental conditions.1,2,3,4 This phenomenon is driven by in utero effects of maternal melatonin5,6,7 on the production of thyrotropin (TSH) in the fetal pars tuberalis (PT) and consequent TSH receptor-mediated effects on tanycytes lining the 3rd ventricle of the mediobasal hypothalamus (MBH).8,9,10 Here we use LASER capture microdissection and transcriptomic profiling to show that TSH-dependent MPP controls the attributes of the ependymal region of the MBH in juvenile animals. In Siberian hamster pups gestated and raised on a long photoperiod (LP) and thereby committed to a fast trajectory for growth and reproductive maturation, the ependymal region is enriched for tanycytes bearing sensory cilia and receptors implicated in metabolic sensing. Contrastingly, in pups gestated and raised on short photoperiod (SP) and therefore following an over-wintering developmental trajectory with delayed sexual maturation, the ependymal region has fewer sensory tanycytes. Post-weaning transfer of SP-gestated pups to an intermediate photoperiod (IP), which accelerates reproductive maturation, results in a pronounced shift toward a ciliated tanycytic profile and formation of tanycytic processes. We suggest that tanycytic plasticity constitutes a mechanism to tailor metabolic development for extended survival in variable overwintering environments.

Integration of mate pair sequences to improve shotgun assemblies of flow-sorted chromosome arms of hexaploid wheat.

BACKGROUND: The assembly of the bread wheat genome sequence is challenging due to allohexaploidy and extreme repeat content (>80%). Isolation of single chromosome arms by flow sorting can be used to overcome the polyploidy problem, but the repeat content cause extreme assembly fragmentation even at a single chromosome level. Long jump paired sequencing data (mate pairs) can help reduce assembly fragmentation by joining multiple contigs into single scaffolds. The aim of this work was to assess how mate pair data generated from multiple displacement amplified DNA of flow-sorted chromosomes affect assembly fragmentation of shotgun assemblies of the wheat chromosomes. RESULTS: Three mate pair (MP) libraries (2 Kb, 3 Kb, and 5 Kb) were sequenced to a total coverage of 89x and 64x for the short and long arm of chromosome 7B, respectively. Scaffolding using SSPACE improved the 7B assembly contiguity and decreased gene space fragmentation, but the degree of improvement was greatly affected by scaffolding stringency applied. At the lowest stringency the assembly N50 increased by ~7 fold, while at the highest stringency N50 was only increased by ~1.5 fold. Furthermore, a strong positive correlation between estimated scaffold reliability and scaffold assembly stringency was observed. A 7BS scaffold assembly with reduced MP coverage proved that assembly contiguity was affected only to a small degree down to ~50% of the original coverage. CONCLUSION: The effect of MP data integration into pair end shotgun assemblies of wheat chromosome was moderate; possibly due to poor contig assembly contiguity, the extreme repeat content of wheat, and the use of amplified chromosomal DNA for MP library construction.

Evidence for adaptive evolution of low-temperature stress response genes in a Pooideae grass ancestor.

Adaptation to temperate environments is common in the grass subfamily Pooideae, suggesting an ancestral origin of cold climate adaptation. Here, we investigated substitution rates of genes involved in low-temperature-induced (LTI) stress responses to test the hypothesis that adaptive molecular evolution of LTI pathway genes was important for Pooideae evolution. Substitution rates and signatures of positive selection were analyzed using 4330 gene trees including three warm climate-adapted species (maize (Zea mays), sorghum (Sorghum bicolor), and rice (Oryza sativa)) and five temperate Pooideae species (Brachypodium distachyon, wheat (Triticum aestivum), barley (Hordeum vulgare), Lolium perenne and Festuca pratensis). Nonsynonymous substitution rate differences between Pooideae and warm habitat-adapted species were elevated in LTI trees compared with all trees. Furthermore, signatures of positive selection were significantly stronger in LTI trees after the rice and Pooideae split but before the Brachypodium divergence (P < 0.05). Genome-wide heterogeneity in substitution rates was also observed, reflecting divergent genome evolution processes within these grasses. Our results provide evidence for a link between adaptation to cold habitats and adaptive evolution of LTI stress responses in early Pooideae evolution and shed light on a poorly understood chapter in the evolutionary history of some of the world's most important temperate crops.

Efficient transfection of Atlantic salmon primary hepatocyte cells for functional assays and gene editing.

The expansion of genomic resources for Atlantic salmon over the past half decade has enabled efficient interrogation of genetic traits by large-scale correlation of genotype to phenotype. Moving from correlation to causation will require genotype-phenotype relationships to be tested experimentally in a cost-efficient and cell context-relevant manner. To enable such future experiments, we have developed a method for the isolation and genetic manipulation of primary hepatocytes from Atlantic salmon for use in heterologous expression, reporter assay, and gene editing experiments. We chose the liver as the tissue of interest because it is the metabolic hub and many current Atlantic salmon research projects focus on understanding metabolic processes to improve traits such as the growth rate, total fat content, and omega-3 content. We find that isolated primary hepatocytes are optimally transfected with both plasmid and ribonucleoprotein using a Neon electroporator at 1,400 V, 10 ms, and 2 pulses. Transfection efficiency with plasmid and cutting efficiency with ribonucleoprotein were optimally 46% and 60%, respectively. We also demonstrate a 26 times increase in luciferase expression under the promoter of the key liver metabolic gene, elovl5b, compared to an empty vector, in line with expected liver-specific expression. Taken together, this work provides a valuable resource enabling transfection and gene editing experiments in a context-relevant and cost-effective system.

Analyses of Genome Regulatory Evolution Following Whole-Genome Duplication Using the Phylogenetic EVE Model.

Whole-genome duplications (WGDs) are important in shaping the evolution of complex genomes, including rewiring of genome regulation. To address key questions about how WGDs impact the evolution of genome regulation, we need to understand the relative importance of selection versus drift and temporal evolutionary dynamics. One promising class of statistical models that can help address such questions are phylogenetic Ornstein-Uhlenbeck (OU) models.Here we present a computational pipeline for the comparative phylogenetic analyses of genome regulation using an OU model. We have implemented this model in R and provide a step-by-step protocol for the use of this model, including example scripts and simulated test data. We provide the nonspecialist a brief overview of how this model works and how to perform tests for signatures of selection on genome regulation as well as power simulations to aid in experimental design and interpretation of results. We believe that these resources could help polyploidy research move forward in an era of rapidly increasing functional genomics data across the tree of life.

Comparative analyses reveal potential uses of Brachypodium distachyon as a model for cold stress responses in temperate grasses.

BACKGROUND: Little is known about the potential of Brachypodium distachyon as a model for low temperature stress responses in Pooideae. The ice recrystallization inhibition protein (IRIP) genes, fructosyltransferase (FST) genes, and many C-repeat binding factor (CBF) genes are Pooideae specific and important in low temperature responses. Here we used comparative analyses to study conservation and evolution of these gene families in B. distachyon to better understand its potential as a model species for agriculturally important temperate grasses. RESULTS: Brachypodium distachyon contains cold responsive IRIP genes which have evolved through Brachypodium specific gene family expansions. A large cold responsive CBF3 subfamily was identified in B. distachyon, while CBF4 homologs are absent from the genome. No B. distachyon FST gene homologs encode typical core Pooideae FST-motifs and low temperature induced fructan accumulation was dramatically different in B. distachyon compared to core Pooideae species. CONCLUSIONS: We conclude that B. distachyon can serve as an interesting model for specific molecular mechanisms involved in low temperature responses in core Pooideae species. However, the evolutionary history of key genes involved in low temperature responses has been different in Brachypodium and core Pooideae species. These differences limit the use of B. distachyon as a model for holistic studies relevant for agricultural core Pooideae species.

Molecular Regulation of Biosynthesis of Long Chain Polyunsaturated Fatty Acids in Atlantic Salmon.

Salmon is a rich source of health-promoting omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). The LC-PUFA biosynthetic pathway in Atlantic salmon is one of the most studied compared to other teleosts. This has largely been due to the massive replacement of LC-PUFA-rich ingredients in aquafeeds with terrestrial plant oils devoid of these essential fatty acids (EFA) which ultimately pushed dietary content towards the minimal requirement of EFA. The practice would also reduce tissue content of n-3 LC-PUFA compromising the nutritional value of salmon to the human consumer. These necessitated detailed studies of endogenous biosynthetic capability as a contributor to these EFA. This review seeks to provide a comprehensive and concise overview of the current knowledge about the molecular genetics of PUFA biosynthesis in Atlantic salmon, highlighting the enzymology and nutritional regulation as well as transcriptional control networks. Furthermore, we discuss the impact of genome duplication on the complexity of salmon LC-PUFA pathway and highlight probable implications on endogenous biosynthetic capabilities. Finally, we have also compiled and made available a large RNAseq dataset from 316 salmon liver samples together with an R-script visualization resource to aid in explorative and hypothesis-driven research into salmon lipid metabolism.

Transkingdom network analysis provides insight into host-microbiome interactions in Atlantic salmon.

BACKGROUND: The Atlantic salmon gut constitutes an intriguing system for studying host-microbiota interactions due to the dramatic environmental change salmon experiences during its life cycle. Yet, little is known about the role of interactions in this system and there is a general deficit in computational methods for integrative analysis of omics data from host-microbiota systems. METHODS: We developed a pipeline to integrate host RNAseq data and microbial 16S rRNA amplicon sequencing data using weighted correlation network analysis. Networks are first inferred from each dataset separately, followed by module detections and finally robust identification of interactions via comparisons of representative module profiles. Through the use of module profiles, this network-based dimensionality reduction approach provides a holistic view into the discovery of potential host-microbiota symbionts. RESULTS: We analyzed host gene expression from the gut epithelial tissue and microbial abundances from the salmon gut in a long-term feeding trial spanning the fresh-/salt-water transition and including two feeds resembling the fatty acid compositions available in salt- and fresh-water environments, respectively. We identified several host modules with significant correlations to both microbiota modules and variables such as feed, growth and sex. Although the strongest associations largely coincided with the fresh-/salt-water transition, there was a second layer of correlations associating smaller host modules to both variables and microbiota modules. Hence, we identify extensive reprogramming of the gut epithelial transcriptome and large scale coordinated changes in gut microbiota composition associated with water type as well as evidence of host-microbiota interactions linked to feed.