Biology subjects

Gronvold, L.

Publications and source records attributed to Gronvold, L..

11 recordsLinked to original sources

bioRxiv2025

Salmonids reveal principles of regulatory evolution following autotetraploidization

Early vertebrate autotetraploidization events may have enabled major innovations by expanding the genetic material for functional diversification, yet their ancient timing obscures how genome doubling reshaped gene regulatory evolution. Salmonids provide a unique window to these mechanisms, because they experienced a comparatively recent autotetraploidization and are earlier in the rediploidization process - which creates new genes and regulatory elements during evolution. Here, using large-scale multiomics spanning embryonic and adult tissues in two salmonids, we investigate gene regulatory evolution following genome doubling and rediploidization, which we show is governed by developmental and tissue-specific context, with a period of maximal constraint at advanced stages of embryogenesis. This work advances understanding of vertebrate genome evolution, while providing an open resource supporting salmonid aquaculture and conservation.

evolutionary biology↗

bioRxiv2025

A major locus on chromosome 14 impacts developmental variation of Atlantic salmon smoltification

BackgroundSmoltification in anadromous Atlantic salmon is a complex developmental process involving physiological and cellular changes that enable freshwater fish to adapt to seawater. Central to this transformation is the functional transformation of the gill to manage osmoregulatory demands. While environmental cues like photoperiod are known to influence smolt development, the genetic architecture underlying smolt development -- particularly related to gill physiology -- remains poorly understood. ResultsA large-scale eQTL analysis across 3,000 Atlantic salmon subjected to three photoperiod regimes, identified over 45,000 significant SNP-gene expression associations in gill tissue. Notably, we discovered a 0.5 Mbp large trans-eQTL hotspot on chromosome 14. This hub-locus was associated with expression of more than 2,000 genes across the genome which were significantly enriched for gill cell type specific markers. In addition we found that the hub-locus was associated with somatic growth. Our findings support a "local tissue effect" model, where cis-regulatory or protein sequence variants within the hub-locus modulate cell proliferation and differentiation of gill cell types. ConclusionThis work advances our understanding of the genetic basis of smoltification in Atlantic salmon and provides a foundation for future studies using single-cell approaches to resolve cell-type specific mechanisms underlying genetic variation in smolt development.

genetics↗

bioRxiv2025

A Nextflow pipeline for molecular quantitative trait loci mapping in small sample size datasets with an application in Atlantic salmon

BackgroundMolecular quantitative trait loci (molQTL) mapping, particularly for gene expression and chromatin accessibility, provides crucial insights into the regulatory and functional potential of genetic variation. While significant progress has been made in humans and model organisms, aquatic genomics remains underexplored due to the large sample sizes typically required for statistical power. ResultsIn this work, we enhance the scalability, reproducibility, and accessibility of the well-established RASQUAL method, which efficiently detects molQTLs in small datasets, by leveraging the Nextflow workflow framework. This adaptation, named nf-RASQUAL, supports fully automated QTL mapping and incorporates a robust, comprehensive multiple-testing correction process. We apply the pipeline to a comprehensive multi-omics dataset from Atlantic salmon, identifying numerous significant expression and chromatin accessibility QTLs across multiple tissues. Our analysis reveals that a large proportion of lead variants for these loci reside in non-coding regions, with caQTL lead SNPs more likely to disrupt transcription factor motifs. Additionally, the enriched colocalization of eQTL and caQTL lead SNPs in brain, liver, and gonad tissues suggests shared regulatory mechanisms. ConclusionsThese findings highlight the scalability and utility of nf-RASQUAL for advancing genetic regulation research in aquaculture, facilitating molQTL studies in less-explored species, and improving our understanding of molecular phenotypes shaped by genetic diversity.

genomics↗

bioRxiv2025

Calcium starvation leads to strain-specific gene regulation of lipid and carotenoid production in Mucor Circinelloides

AO_SCPLOWBSTRACTC_SCPLOWFungi are pivotal in transitioning to a bio-based, circular economy due to their ability to transform organic material into valuable products such as organic acids, enzymes, and drugs. Mucor circinelloides is a model organism for studying lipogenesis and it particularly promising for its metabolic capabilities in producing oils like TAGs and carotenoids, influenced by environmental factors such as nutrient availability. Notably, strains VI04473 and FRR5020 have been identified for their potential in producing single-cell oils and carotenoids, respectively. Calcium starvation have previously been shown to have strain-specific effects, with VI04473 accumulating more lipids and FRR5020 producing more carotenoids. Here we used genome sequencing, comparative genomics, transcriptomics, and metabolite phenotyping to explore the genetic basis of lipid and carotenoid production under calcium starvation in these strains. We found extensive genomic rearrangements between these strains, as well as low conservation of gene regulatory responses to calcium depletion. This lack of conservation also applies to genes involved in lipid and carotenoid production, i.e. the lipidome. Several pathways show divergent regulation between strains, which explains the phenotypic divergence between VI04473 and FRR5020. The complex gene family evolution of several lipidome genes probably also affected specialization of these strains to calcium stress. Our study sheds light on the complexity of the evolution of metabolic networks in M. circinelloides. Understanding these genetic underpinnings can optimize the industrial use of M. circinelloides, enhancing lipid productivity and stress tolerance, and tailoring metabolic profiles for specific applications. This research advances our knowledge on complexity of fungal lipid metabolism and the role of calcium in regulating metabolic pathways.

genomics↗

bioRxiv2025

Sequence-based chromatin activity modeling and regulatory impact prediction of genetic variants in farmed animals using deep learning

Non-coding genomic variations are crucial for the genetic regulation of traits; how-ever, their functional impact in farmed animals remains underexplored due to lim-ited genomic resources and the absence of tailored computational tools. Here, we present a deep learning-based framework that utilizes functional genomics data to generate genome-wide predictions of the regulatory impact of non-coding vari-ants in cattle, chicken, pig, and Atlantic salmon. By leveraging chromatin profiles such as ATAC, DHS, and ChIP-seq data, we train and optimize separate deep networks for each species, achieving robust sequence modeling accuracy specific to each. Motif analysis confirms that the models capture regulatory grammar, while in silico saturation mutagenesis experiments provide meaningful interpretations of the functional impact of putative causal variants. Furthermore, functional scores derived from these models predict eQTL causal variants and enhance genomic prediction performance. Our findings highlight the transformative potential of se-quence to function models in prioritizing causal variants and improving genomic prediction for livestock and aquaculture.

genomics↗

bioRxiv2024

Transcriptomic profiling of gill biopsies to define predictive markers for seawater survival in farmed Atlantic salmon

Wild Atlantic salmon migrate to sea following completion of a developmental process known as parr - smolt transformation (PST), which establishes a seawater (SW) tolerant phenotype. Effective imitation of this aspect of anadromous life-history is a crucial aspect of commercial salmon production, with current industry practice being marred by significant losses during transition from the freshwater (FW) to SW phase of production. The natural photoperiodic control of PST can be mimicked by exposing farmed juvenile fish to a reduced duration photoperiod for at least 6 weeks before increasing the photoperiod in the last 1 - 2 months before SW transfer. While it is known that variations in this general protocol affect subsequent SW performance, there is no uniformly accepted industry standard; moreover, reliable prediction of SW performance from fish attributes in the FW phase remains a major challenge. Here we describe an experiment in which we took gill biopsies 1 week prior to SW transfer from 3000 individually tagged fish raised on 3 different photoperiod regimes during the FW phase. Biopsies were subjected to RNA profiling by Illumina sequencing, while individual fish growth and survival was monitored over 300 days in a SW cage environment, run as a common garden experiment. Using a random forest machine learning algorithm, we developed gene expression-based predictive models for initial survival and stunted growth in SW. Stunted growth phenotypes could not be predicted based on gill transcriptomes, but survival the first 40 days in SW could be predicted with moderate accuracy. While several previously identified marker genes contribute to this model, a surprisingly low weighting is ascribed to sodium potassium ATPase subunit genes, contradicting advocacy for their use as SW readiness markers. However, genes with photoperiod-history sensitive regulation were highly enriched among the genes with highest importance in the prediction model. This work opens new avenues for understanding and exploiting developmental changes in gill physiology during smolt development.

genomics↗

bioRxiv2024

The role of transposon activity in shaping cis-regulatory element evolution after whole genome duplication

Two of the most potent drivers of genome evolution in eukaryotes are whole genome duplications (WGD) and transposable element (TE) activity. These two mutational forces can also play synergistic roles; WGDs result in both cellular stress and functional redundancy, which would allow TEs to escape host-silencing mechanisms and effectively spread with reduced impact on fitness. As TEs can function as, or evolve into, TE-derived cis-regulatory elements (TE-CREs), bursts of TE-activity following WGD are likely to impact evolution of gene regulation. However, the role of TEs in genome regulatory remodelling after WGDs is unclear. Here we used the genome of Atlantic salmon, which is known to have experienced massive expansion of TEs after a WGD [~]100 Mya, as a model system to explore the synergistic roles of TEs and WGDs on genome regulatory evolution. We identified 55,080 putative TE-CREs in Atlantic salmon using chromatin accessibility data from brain and liver. Of these, 80% were tissue specific to liver (43%) or brain (37%) and TE-CREs originating from retroelements were twice as common as those originating from DNA elements. Signatures of selection shaping TE-CRE evolution were evident from depletion of TEs in open chromatin, a bias in tissue-shared TE-CREs towards older TE-insertions, as well as tissue-specific processes shaping the TE-CRE repertoire. A minority of TE-families (16%) accounted for the origin of 46% of all TE-CREs, but the transposition activity of these CRE-superspreader families happened mostly prior to the WGD. Analyses of individual TE-CREs do however support a significantly higher rate of TE-CRE evolution from insertions happening around the time of the salmonid WGD. This pattern was particularly striking for the DTT elements, despite having generally low propensity to evolve into TE-CREs and impact transcription. Furthermore, co-expression based analyses supported the presence of TE-driven gene regulatory network evolution, including DTT elements active at the time of WGD. In conclusion, we find a strong association between TE insertions at the time of WGD and TE-CRE evolution. This association was not driven by particular TE-families with high capability to evolve into TE-CREs but likely a consequence of the concurrent surge of novel TE insertions, mostly from DTT elements, in combination with a shift in selective pressure on genome regulation following the WGD.

evolutionary biology↗

bioRxiv2023

High radiosensitivity in Norway spruce (Picea abies) is rendered by less comprehensive mobilisation of protection, repair and stress responses compared to the radiotolerant A. thaliana

Risk assessment and protection of plant communities in contaminated ecosystems require in-depth understanding of differential sensitivity to chronic ionising radiation in plants. However, the contributing molecular factors to differential radiosensitivity among plant species are poorly understood. To shed light on this, we compared early events associated with protection, repair, and stress responses in gamma-irradiated (1-290 mGy h-1) seedlings of the radiosensitive conifer Norway spruce (Picea abies) and the radiotolerant Arabidopsis thaliana, by analysing growth, organelle and DNA damage, transcriptomes and the dynamics of antioxidant activities and expression of relevant genes. After 48 h of gamma radiation exposure, Norway spruce showed significantly reduced growth at 100-290 mGy h-1 and organelle damage, especially in mitochondria, at [≥] 1 mGy h-1 whereas A. thaliana showed normal vegetative growth at all dose rates, transiently delayed reproductive development at 290 mGy h-1 only, minor organelle damage only at [≥] 100 mGy h-1 and significantly less DNA damage than in Norway spruce at all dose rates. Comparative transcriptomics revealed that A. thaliana showed massive activation of genes related to DNA damage repair, antioxidants, and other stress responses at [≥] 1 mGy h-1 while Norway spruce mobilized transcription of such pathways only at [≥] 40 mGy h-1. The transcriptional activation of repair and protection responses at higher gamma dose-rates only and its absence in lower dose-rates, correlates with high radiosensitivity of Norway spruce, compared to the massive transcriptional activation from low dose-rates in the radiotolerant A. thaliana.

plant biology↗

bioRxiv2023

Linking genomic prediction for muscle fat content in Atlantic salmon to underlying changes in lipid metabolism regulation

Muscle fat content is an important production trait in Atlantic salmon (Salmo salar) because it influences the flavor, texture, and nutritional properties of the fillet. Genomic selection can be applied to alter muscle fat content, however how such selection changes the underlying molecular physiology of these animals is unknown. Here, we examine the link between genomic prediction and underlying molecular physiology by correlating genomic breeding values for fat content to liver gene expression in 184 fish. We found that Salmon with higher genomic breeding values had higher expression of genes in lipid metabolism pathways. This included key lipid metabolism genes hmgcrab, fasn-b, fads2d5, and fads2d6, and lipid transporters fatp2f, fabp7b, and apobc. We also found several regulators of lipid metabolism with negative correlation to genomic breeding vales, including pparg-b, fxr-a, and fxr-b. A quantitative trait loci analysis for variation in gene expression levels (eQTLs) for 167 trait associated genes found that 71 genes had at least one eQTL, and that most were trans eQTLs. Closer examination revealed distinct eQTL clustering on chromosomes 3 and 6, indicating the presence of putative common regulator in these regions. Taken together, these results suggest that increased fat content in high genomic breeding value salmon is associated with elevated lipid synthesis, elevated lipid transport, and reduced glycerolipid breakdown; and that this is at least partly achieved by selection on genetic variants that impact the function of top-level transcription factors involved in liver metabolism. Our study sheds light on how genomic selection alters lipid content in Atlantic salmon, and the results could be used to prioritize SNPs to improve the efficiency of genomic selection in the future.

genomics↗

bioRxiv2023

Functional and regulatory diversification of circadian rhythm period genes during the evolution of vertebrates

The Period genes (Per) play essential roles in modulating the molecular circadian clock timing in a broad range of species, which regulates the physiological and cellular through the transcription-translation feedback loop. While the Period gene paralogs are widely observed among vertebrates, the evolutionary history and the functional diversification of Per genes across vertebrates are not well known. In this study, we comprehensively investigated the evolution of Per genes, including de novo binding motif discovery by comparative genomics. We also determined the lineage-specific transcriptome landscape across tissues and developmental stages and phenotypic effects in public RNA-seq data sets of model species. We observed multiple lineage-specific gain and loss events of Per genes, though no simple association was observed between ecological factors and Per gene numbers in each species. Among salmonid fish species, the per3 gene has been lost in the majority, whereas those retaining the per3 gene exhibit not a signature of relaxed selective constraint but rather a signature of intensified selection. We also determined the signature of adaptive diversification of the CRY-binding region in Per1 and Per3, which modulates the circadian rhythm. We also discovered putative regulatory sequences, which are lineage-specific, suggesting that these cis-regulatory elements may have evolved rapidly and divergently across different lineages. Collectively, our findings revealed the evolution of Per genes and their fine-tuned contribution to the plastic and precise regulation of circadian rhythms in various vertebrate taxa. SignificanceThe Period (Per) genes play essential roles in the circadian rhythm in animals. In this study, we comprehensively investigated the evolutionary diversification of the three types of Period genes in vertebrates. As a result, we observed a rapid evolution and sub-functionalization of these genes, especially adaptive diversification signatures in the protein-binding region, which plays a crucial role in regulating circadian rhythms. This underscores the fine-tuned contribution of Per genes in the biological clocks precision and adaptability across various vertebrate taxa.

evolutionary biology↗

bioRxiv2021

Genome-wide reconstruction of rediploidization following autopolyploidizationacross 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 (ohnologues) 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 ohnologue 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 ohnologue 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 Mya). This was followed by a period of relative genomic stasis lasting 17-39 My, where much of the genome remained in a tetraploid state. A second rediploidization wave began in the early Eocene and proceeded alongside species diversification, generating predictable patterns of lineage-specific ohnologue divergence, scaling in complexity with the number of speciation events. Finally, using gene set enrichment, gene expression, and codon-based selection analyses, we provide insights into potential functional outcomes of delayed rediploidization. Overall, this study enhances our understanding of delayed autopolyploid rediploidization and has broad implications for future studies of WGD events.

genomics↗