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.

Insertion of an endogenous Jaagsiekte sheep retrovirus element into the BCO2 - gene abolishes its function and leads to yellow discoloration of adipose tissue in Norwegian Spælsau (Ovis aries).

BACKGROUND: The accumulation of carotenoids in adipose tissue leading to yellow fat is, in sheep, a heritable recessive trait that can be attributed to a nonsense mutation in the beta-carotene oxygenase 2 (BCO2) gene. However, not all sheep breeds suffering from yellow fat have this nonsense mutation, meaning that other functional mechanisms must exist. We investigated one such breed, the Norwegian spælsau. RESULTS: In spælsau we detected an aberration in BCO2 mRNA. Nanopore sequencing of genomic DNA revealed the insertion of a 7.9 kb endogenous Jaagsiekte Sheep Retrovirus (enJSRV) sequence in the first intron of the BCO2 gene. Close examination of its cDNA revealed that the BCO2 genes first exon was spliced together with enJSRV-sequence immediately downstream of a potential -AG splice acceptor site at enJSRV position 415. The hybrid protein product consists of 29 amino acids coded by the BCO2 exon 1, one amino acid coded by the junction sequence, followed by 28 amino acids arbitrary coded for by the enJSRV-sequence, before a translation stop codon is reached. CONCLUSIONS: Considering that the functional BCO2 protein consists of 575 amino acids, it is unlikely that the 58 amino acid BCO2/enJSRV hybrid protein can display any enzymatic function. The existence of this novel BCO2 allele represents an alternative functional mechanism accounting for BCO2 inactivation and is a perfect example of the potential benefits for searching for structural variants using long-read sequencing data.

Demyelinating polyneuropathy in goats lacking prion protein.

Studies in mice with ablation of Prnp, the gene that encodes the cellular prion protein (PrPC ), have led to the hypothesis that PrPC is important for peripheral nerve myelin maintenance. Here, we have used a nontransgenic animal model to put this idea to the test; namely, goats that, due to a naturally occurring nonsense mutation, lack PrPC . Teased nerve fiber preparation revealed a demyelinating pathology in goats without PrPC . Affected nerves were invaded by macrophages and T cells and displayed vacuolated fibers, shrunken axons, and onion bulbs. Peripheral nerve lipid composition was similar in young goats with or without PrPC , but markedly different between corresponding groups of adult goats, reflecting the progressive nature of the neuropathy. This is the first report of a subclinical demyelinating polyneuropathy caused by loss of PrPC function in a nontransgenic mammal.

Genomic regions and signaling pathways associated with indicator traits for feed efficiency in juvenile Atlantic salmon (Salmo salar).

BACKGROUND: One objective of this study was to identify putative quantitative trait loci (QTL) that affect indicator phenotypes for growth, nitrogen, and carbon metabolism in muscle, liver, and adipose tissue, and for feed efficiency. Another objective was to perform an RNAseq analysis (184 fish from all families), to identify genes that are associated with carbon and nitrogen metabolism in the liver. The material consisted of a family experiment that was performed in freshwater and included 2281 individuals from 23 full-sib families. During the 12-day feed conversion test, families were randomly allocated to family tanks (50 fish per tank and 2 tanks per family) and fed a fishmeal-based diet labeled with the stable isotopes 15N and 13C at inclusion levels of 2 and 1%, respectively. RESULTS: Using a linear mixed-model algorithm, a QTL for pre-smolt growth was identified on chromosome 9 and a QTL for carbon metabolism in the liver was identified on chromosome 12 that was closely related to feed conversion ratio on a tank level. For the indicators of feed efficiency traits that were derived from the stable isotope ratios (15N and 13C) of muscle tissue and growth, no convincing QTL was detected, which suggests that these traits are polygenic. The transcriptomic analysis showed that high carbon and nitrogen metabolism was associated with individuals that convert protein from the feed more efficiently, primarily due to higher expression of the proteasome, lipid, and carbon metabolic pathways in liver. In addition, we identified seven transcription factors that were associated with carbon and nitrogen metabolism and located in the identified QTL regions. CONCLUSIONS: Analyses revealed one QTL associated with pre-smolt growth and one QTL for carbon metabolism in the liver. Both of these traits are associated with feed efficiency. However, more accurate mapping of the putative QTL will require a more diverse family material. In this experiment, fish that have a high carbon and nitrogen metabolism in the liver converted protein from the feed more efficiently, potentially because of a higher expression of the proteasome, lipid, and carbon metabolic pathways in liver. Within the QTL regions, we detected seven transcription factors that were associated with carbon and nitrogen metabolism.

Transcriptome profiling of porcine testis tissue reveals genes related to sperm hyperactive motility.

BACKGROUND: Sperm hyperactive motility has previously been shown to influence litter size in pigs, but little is known about the underlying biological mechanisms. The aim of this study was to use RNA sequencing to investigate gene expression differences in testis tissue from Landrace and Duroc boars with high and low levels of sperm hyperactive motility. Boars with divergent phenotypes were selected based on their sperm hyperactivity values at the day of ejaculation (day 0) (contrasts (i) and (ii) for Landrace and Duroc, respectively) and on their change in hyperactivity between day 0 and after 96 h liquid storage at 18 °C (contrast (iii)). RESULTS: RNA sequencing was used to measure gene expression in testis. In Landrace boars, 3219 genes were differentially expressed for contrast (i), whereas 102 genes were differentially expressed for contrast (iii). Forty-one differentially expressed genes were identified in both contrasts, suggesting a functional role of these genes in hyperactivity regardless of storage. Zinc finger DNLZ was the most up-regulated gene in contrasts (i) and (iii), whereas the most significant differentially expressed gene for the two contrasts were ADP ribosylation factor ARFGAP1 and solute carrier SLC40A1, respectively. For Duroc (contrast (ii)), the clustering of boars based on their gene expression data did not reflect their difference in sperm hyperactivity phenotypes. No results were therefore obtained for this breed. A case-control analysis of variants identified in the Landrace RNA sequencing data showed that SNPs in NEU3, CHRDL2 and HMCN1 might be important for sperm hyperactivity. CONCLUSIONS: Differentially expressed genes were identified in Landrace boars with high and low levels of sperm hyperactivity at the day of ejaculate collection and high and low change in hyperactivity after 96 h of sperm storage. The results point towards important candidate genes, biochemical pathways and sequence variants underlying sperm hyperactivity in pigs.

SalMotifDB: a tool for analyzing putative transcription factor binding sites in salmonid genomes.

BACKGROUND: Recently developed genome resources in Salmonid fish provides tools for studying the genomics underlying a wide range of properties including life history trait variation in the wild, economically important traits in aquaculture and the evolutionary consequences of whole genome duplications. Although genome assemblies now exist for a number of salmonid species, the lack of regulatory annotations are holding back our mechanistic understanding of how genetic variation in non-coding regulatory regions affect gene expression and the downstream phenotypic effects. RESULTS: We present SalMotifDB, a database and associated web and R interface for the analysis of transcription factors (TFs) and their cis-regulatory binding sites in five salmonid genomes. SalMotifDB integrates TF-binding site information for 3072 non-redundant DNA patterns (motifs) assembled from a large number of metazoan motif databases. Through motif matching and TF prediction, we have used these multi-species databases to construct putative regulatory networks in salmonid species. The utility of SalMotifDB is demonstrated by showing that key lipid metabolism regulators are predicted to regulate a set of genes affected by different lipid and fatty acid content in the feed, and by showing that our motif database explains a significant proportion of gene expression divergence in gene duplicates originating from the salmonid specific whole genome duplication. CONCLUSIONS: SalMotifDB is an effective tool for analyzing transcription factors, their binding sites and the resulting gene regulatory networks in salmonid species, and will be an important tool for gaining a better mechanistic understanding of gene regulation and the associated phenotypes in salmonids. SalMotifDB is available at https://salmobase.org/apps/SalMotifDB .

SalmoBase: an integrated molecular data resource for Salmonid species.

BACKGROUND: Salmonids are ray-finned fishes which constitute 11 genera and at least 70 species including Atlantic salmon, whitefishes, graylings, rainbow trout, and char. The common ancestor of all Salmonidae experienced a whole genome duplication (WGD) ~80 million years ago, resulting in an autotetraploid genome. Genomic rediplodization is still going on in salmonid species, providing an unique system for studying evolutionary consequences of whole genome duplication. In recent years, high quality genome sequences of Atlantic salmon and Rainbow trout has been established, due to their scientific and commercial values. In this paper we introduce SalmoBase ( http://www.salmobase.org/ ), a tool for making molecular resources for salmonids public available in a framework of visualizations and analytic tools. RESULTS: SalmoBase has been developed as a part of the ELIXIR.NO project. Currently, SalmoBase contains molecular resources for Atlantic salmon and Rainbow trout. Data can be accessed through BLAST, Genome Browser (GBrowse), Genetic Variation Browser (GVBrowse) and Gene Expression Browser (GEBrowse). CONCLUSIONS: To the best of our knowledge, SalmoBase is the first database which integrates salmonids data and allow users to study salmonids in an integrated framework. The database and its tools (e.g., comparative genomics tools, synteny browsers) will be expanded as additional public resources describing other Salmonidae genomes become available.

RNA sequencing reveals candidate genes and polymorphisms related to sperm DNA integrity in testis tissue from boars.

BACKGROUND: Sperm DNA is protected against fragmentation by a high degree of chromatin packaging. It has been demonstrated that proper chromatin packaging is important for boar fertility outcome. However, little is known about the molecular mechanisms underlying differences in sperm DNA fragmentation. Knowledge of sequence variation influencing this sperm parameter could be beneficial in selecting the best artificial insemination (AI) boars for commercial production. The aim of this study was to identify genes differentially expressed in testis tissue of Norwegian Landrace and Duroc boars, with high and low sperm DNA fragmentation index (DFI), using transcriptome sequencing. RESULTS: Altogether, 308 and 374 genes were found to display significant differences in expression level between high and low DFI in Landrace and Duroc boars, respectively. Of these genes, 71 were differentially expressed in both breeds. Gene ontology analysis revealed that significant terms in common for the two breeds included extracellular matrix, extracellular region and calcium ion binding. Moreover, different metabolic processes were enriched in Landrace and Duroc, whereas immune response terms were common in Landrace only. Variant detection identified putative polymorphisms in some of the differentially expressed genes. Validation showed that predicted high impact variants in RAMP2, GIMAP6 and three uncharacterized genes are particularly interesting for sperm DNA fragmentation in boars. CONCLUSIONS: We identified differentially expressed genes between groups of boars with high and low sperm DFI, and functional annotation of these genes point towards important biochemical pathways. Moreover, variant detection identified putative polymorphisms in the differentially expressed genes. Our results provide valuable insights into the molecular network underlying DFI in pigs.

Genetic diversity and historical demography of underutilised goat breeds in North-Western Europe.

In the last decade, several studies aimed at dissecting the genetic architecture of local small ruminant breeds to discover which variations are involved in the process of adaptation to environmental conditions, a topic that has acquired priority due to climate change. Considering that traditional breeds are a reservoir of such important genetic variation, improving the current knowledge about their genetic diversity and origin is the first step forward in designing sound conservation guidelines. The genetic composition of North-Western European archetypical goat breeds is still poorly exploited. In this study we aimed to fill this gap investigating goat breeds across Ireland and Scandinavia, including also some other potential continental sources of introgression. The PCA and Admixture analyses suggest a well-defined cluster that includes Norwegian and Swedish breeds, while the crossbred Danish landrace is far apart, and there appears to be a close relationship between the Irish and Saanen goats. In addition, both graph representation of historical relationships among populations and f4-ratio statistics suggest a certain degree of gene flow between the Norse and Atlantic landraces. Furthermore, we identify signs of ancient admixture events of Scandinavian origin in the Irish and in the Icelandic goats. The time when these migrations, and consequently the introgression, of Scandinavian-like alleles occurred, can be traced back to the Viking colonisation of these two isles during the Viking Age (793-1066 CE). The demographic analysis indicates a complicated history of these traditional breeds with signatures of bottleneck, inbreeding and crossbreeding with the improved breeds. Despite these recent demographic changes and the historical genetic background shaped by centuries of human-mediated gene flow, most of them maintained their genetic identity, becoming an irreplaceable genetic resource as well as a cultural heritage.

Protein profiling of testicular tissue from boars with different levels of hyperactive sperm motility.

Hyperactive sperm motility is important for successful fertilization. In the present study, a proteome profiling approach was performed to identify the differences between Landrace boars with different levels of hyperactive sperm motility in liquid extended semen. Two contrasts were studied: (i) high versus low levels of sperm hyperactivity at semen collection day and (ii) high versus low change in levels of sperm hyperactivity after 96 h semen storage. Testicular samples were analyzed on a Q Exactive mass spectrometer and more than 6000 proteins were identified in the 13 samples. The most significant differentially expressed proteins were mediator complex subunit 28 (MED28), cell division cycle 37 like 1 (CDC37L1), ubiquitin specific peptidase 10 (USP10), zinc finger FYVE-type containing 26 (ZFYVE26), protein kinase C delta (PRKCD), actinin alpha 4 (ACTN4), N(alpha)-acetyltransferase 30 (NAA30), C1q domain-containing (LOC110258309) and uncharacterized LOC100512926. Of the differentially expressed proteins, 11 have previously been identified as differentially expressed at the corresponding mRNA transcript level using the same samples and contrasts. These include sphingosine kinase 1 isoform 2 (SPHK1), serine and arginine rich splicing factor 1 (SRSF1), and tubulin gamma-1 (TUBG1) which are involved in the acrosome reaction and sperm motility. A mass spectrometry approach was applied to investigate the protein profiles of boars with different levels of hyperactive sperm motility. This study identified several proteins previously shown to be involved in sperm motility and quality, but also proteins with no known function for sperm motility. Candidates that are differentially expressed on both mRNA and protein levels are especially relevant as biological markers of semen quality.

Characterisation of a novel paralog of scavenger receptor class B member I (SCARB1) in Atlantic salmon (Salmo salar).

BACKGROUND: Red flesh colour is a unique trait found in some salmonid genera. Carotenoid pigments are not synthesized de novo in the fish, but are provided by dietary uptake. A better understanding of the molecular mechanisms underlying the cellular uptake and deposition of carotenoids could potentially be used to improve the low muscle deposition rate that is typically found in farmed Atlantic salmon. In addition, from an evolutionary point of view, the establishment and maintenance of this trait is still poorly understood. It has been demonstrated in several species that scavenger receptor class B, member 1 (SCARB1) is involved in intestinal absorption of carotenoids, which makes this gene a possible source of genetic variation in salmonid flesh pigmentation. RESULTS: In this study, a novel paralog of SCARB1 (SCARB1-2) was detected through screening for genetic variation in Atlantic salmon SCARB1. Full length SCARB1-2 encodes a protein with 89% identity to Atlantic salmon SCARB1, except for the C-terminal cytoplasmic tail that shows only 12% identity. The most prominent site of SCARB1 mRNA expression was in the mid gut, while a five-fold lower level was detected in Atlantic salmon skeletal muscle and liver. The SCARB1-2 mRNA was equally expressed in liver, muscle and mid gut, and at a lower level than SCARB1 mRNA. A total of seven different SCARB1-2 alleles comprising repetitive enhancer of zeste motifs (EZH2) were identified in the founding parents of a resource Atlantic salmon population. We mapped the SCARB1-2 paralog to a region on Atlantic salmon chromosome 1, containing a putative QTL for flesh colour. Addition of the SCARB1-2 marker increased the significance of this QTL, however the large confidence interval surrounding the QTL precludes confirmation of SCARB1-2 as a causative gene underlying variation in this trait. CONCLUSION: We have characterised a novel paralog of SCARB1 (SCARB1-2), have mapped it to Atlantic salmon chromosome 1 and have described its expression in various tissues. Mapping with SCARB1-2 alleles added further evidence for a QTL affecting flesh colour on this chromosome, however further studies are needed to confirm a functional role for this gene in flesh colour pigmentation.

Mapping of quantitative trait loci for flesh colour and growth traits in Atlantic salmon (Salmo salar).

BACKGROUND: Flesh colour and growth related traits in salmonids are both commercially important and of great interest from a physiological and evolutionary perspective. The aim of this study was to identify quantitative trait loci (QTL) affecting flesh colour and growth related traits in an F2 population derived from an isolated, landlocked wild population in Norway (Byglands Bleke) and a commercial production population. METHODS: One hundred and twenty-eight informative microsatellite loci distributed across all 29 linkage groups in Atlantic salmon were genotyped in individuals from four F2 families that were selected from the ends of the flesh colour distribution. Genotyping of 23 additional loci and two additional families was performed on a number of linkage groups harbouring putative QTL. QTL analysis was performed using a line-cross model assuming fixation of alternate QTL alleles and a half-sib model with no assumptions about the number and frequency of QTL alleles in the founder populations. RESULTS: A moderate to strong phenotypic correlation was found between colour, length and weight traits. In total, 13 genome-wide significant QTL were detected for all traits using the line-cross model, including three genome-wide significant QTL for flesh colour (Chr 6, Chr 26 and Chr 4). In addition, 32 suggestive QTL were detected (chromosome-wide P < 0.05). Using the half-sib model, six genome-wide significant QTL were detected for all traits, including two for flesh colour (Chr 26 and Chr 4) and 41 suggestive QTL were detected (chromosome-wide P < 0.05). Based on the half-sib analysis, these two genome-wide significant QTL for flesh colour explained 24% of the phenotypic variance for this trait. CONCLUSIONS: A large number of significant and suggestive QTL for flesh colour and growth traits were found in an F2 population of Atlantic salmon. Chr 26 and Chr 4 presented the strongest evidence for significant QTL affecting flesh colour, while Chr 10, Chr 5, and Chr 4 presented the strongest evidence for significant QTL affecting growth traits (length and weight). These QTL could be strong candidates for use in marker-assisted selection and provide a starting point for further characterisation of the genetic components underlying flesh colour and growth.

When parameters in dynamic models become phenotypes: a case study on flesh pigmentation in the chinook salmon (Oncorhynchus tshawytscha).

The Pacific chinook salmon occurs as both white- and red-fleshed populations, with the flesh color type (red or white) seemingly under strong genetic influence. Previously published data on crosses between red- and white-fleshed individuals cannot be reconciled with a simple Mendelian two-locus, two-allele model, pointing to either a more complex inheritance pattern or the existence of gene interactions. Here we show that a standard single-locus, three-allele model can fully explain these data. Moreover, by implementing the single-locus model at the parameter level of a previously developed mathematical model describing carotenoid dynamics in salmon, we show that variation at a single gene involved in the muscle uptake of carotenoids is able to explain the available data. This illustrates how such a combined approach can generate biological understanding that would not be possible in a classical population genetic explanatory structure. An additional asset of this approach is that by allowing parameters to become phenotypes obeying a given genetic model, biological interpretations of mechanisms involved at a resolution level far beyond what is built into the original dynamic model are made possible. These insights can in turn be exploited in experimental studies as well as in construction of more detailed models.

Association between single-nucleotide polymorphisms within candidate genes and fertility in Landrace and Duroc pigs.

Finding effective predictors of traits related to boar fertility is essential for increasing the efficiency of artificial insemination systems in pig breeding. The objective of this study was to find associations between single-nucleotide polymorphisms (SNPs) within candidate genes and fertility in the breeds Landrace and Duroc. Animals with breeding values for total number of piglets born, were re-sequenced for exonic regions of 14 candidate genes related to male and female fertility using samples from 16 Landrace boars and 16 Duroc boars (four with high and four with low breeding value of total number of piglets born for each breed for male fertility, and the same for female fertility) to detect genetic variants. Genotyping for the detected SNPs was done in 619 Landrace boars and 513 Duroc boars. Two SNPs in BMPR1 and one SNP in COX-2 were found significantly associated with the total number of piglets born in Landrace. In Duroc, two SNPs in PLCz, one SNP in VWF and one SNP in ZP3 were found significantly associated with total number of piglets born. These SNPs explained between 0.27% and 1.18% of the genetic variance. These effects are too low for being used directly for selection purposes but can be of interest in SNP-panels used for genomic selection.

Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color.

Red coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL- region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

Relationship between sperm motility characteristics and ATP concentrations, and association with fertility in two different pig breeds.

Boar fertility has a major impact on overall pig reproductive efficiency. Using accurate and objective in vitro sperm variables for predicting in vivo fertility from a single ejaculate, however, is challenging. Motility is the most widely used indicator of sperm quality, and a computer assisted sperm analysis (CASA) system is now available for objective assessment of sperm motility characteristics. In this study sperm motility characteristics and semen ATP concentrations were investigated and the effect of both were evaluated on total number of piglets born (TNB) when Norwegian Landrace (NL) and Norwegian Duroc (ND) boar semen was used for AI. In addition, breed differences for semen storage capacity were investigated. The results from CASA analysis indicated there were differences between NL and ND sperm motility variables. The percentage of motile sperm cells decreased in both NL (P = 0.01) and ND (P < 0.0001) during storage. A large proportion of sperm cells with a hyperactive motility pattern were detected in ND semen on the day of collection, with no significant changes as a result of storage. Inconsistent with this finding, there was greater degree of hyper-activation in sperm motility pattern for NL because of semen storage. There was a significant decrease in semen ATP concentration during storage (P < 0.0001) in both breeds. The linearity of sperm movement at the day of collection and the wobble after storage influenced TNB in NL, while the percentage of motile cells, curvilinear velocity and lateral head amplitude on the day of semen collection and linearity after storage influenced TNB in ND.

Norwegian e-Infrastructure for Life Sciences (NeLS).

The Norwegian e-Infrastructure for Life Sciences (NeLS) has been developed by ELIXIR Norway to provide its users with a system enabling data storage, sharing, and analysis in a project-oriented fashion. The system is available through easy-to-use web interfaces, including the Galaxy workbench for data analysis and workflow execution. Users confident with a command-line interface and programming may also access it through Secure Shell (SSH) and application programming interfaces (APIs).  NeLS has been in production since 2015, with training and support provided by the help desk of ELIXIR Norway. Through collaboration with NorSeq, the national consortium for high-throughput sequencing, an integrated service is offered so that sequencing data generated in a research project is provided to the involved researchers through NeLS. Sensitive data, such as individual genomic sequencing data, are handled using the TSD (Services for Sensitive Data) platform provided by Sigma2 and the University of Oslo. NeLS integrates national e-infrastructure storage and computing resources, and is also integrated with the SEEK platform in order to store large data files produced by experiments described in SEEK.   In this article, we outline the architecture of NeLS and discuss possible directions for further development.

Carotenoid dynamics in Atlantic salmon.

BACKGROUND: Carotenoids are pigment molecules produced mainly in plants and heavily exploited by a wide range of organisms higher up in the food-chain. The fundamental processes regulating how carotenoids are absorbed and metabolized in vertebrates are still not fully understood. We try to further this understanding here by presenting a dynamic ODE (ordinary differential equation) model to describe and analyse the uptake, deposition, and utilization of a carotenoid at the whole-organism level. The model focuses on the pigment astaxanthin in Atlantic salmon because of the commercial importance of understanding carotenoid dynamics in this species, and because deposition of carotenoids in the flesh is likely to play an important life history role in anadromous salmonids. RESULTS: The model is capable of mimicking feed experiments analyzing astaxanthin uptake and retention over short and long time periods (hours, days and years) under various conditions. A sensitivity analysis of the model provides information on where to look for possible genetic determinants underlying the observed phenotypic variation in muscle carotenoid retention. Finally, the model framework is used to predict that a specific regulatory system controlling the release of astaxanthin from the muscle is not likely to exist, and that the release of the pigment into the blood is instead caused by the androgen-initiated autolytic degradation of the muscle in the sexually mature salmon. CONCLUSION: The results show that a dynamic model describing a complex trait can be instrumental in the early stages of a project trying to uncover underlying determinants. The model provides a heuristic basis for an experimental research programme, as well as defining a scaffold for modelling carotenoid dynamics in mammalian systems.

Genomic organization and transcript profiling of the bovine toll-like receptor gene cluster TLR6-TLR1-TLR10.

Toll-like receptors (TLRs) are a family of recognition receptors playing a crucial role in the innate immune system. Different combinations of TLRs are thought to be crucial for effective immune response, thus insight into the organization and expression of TLRs is important for understanding disease resistance. Mastitis is the most frequent and costly disease in dairy production, and the innate immune system is considered to be important in the first line defence against this disease. In the present paper we have characterized the genomic organization of TLR6-TLR1-TLR10 in a approximately 50 kb region of bovine chromosome 6, including 5'-untranslated exons not previously described. A method for gene expression analysis was developed and used for transcription profiling of the three paralogous genes in different bovine tissues. The expression analysis showed similar expression profiles for TLR1 and TLR6, which indicate a co-regulation of these two genes in cattle. TLR10 had a different expression profile, pointing toward a stronger functional diversification compared to TLR1 and TLR6. The differences in expression are in accordance with the evolutionary history of this gene cluster, where TLR10 diverged from the common ancestral gene before the duplication event that created TLR1 and TLR6.