Biology subjects

Lien, S.

Publications and source records attributed to Lien, S..

At least 19 recordsLinked to original sources

bioRxiv2026

PRDM9 Alleles Guide Distinct Patterns of Recombination Localization in Atlantic Salmon

Meiotic recombination in many vertebrate lineages is directed to genomic regions by the DNA-binding protein PRDM9. To date, PRDM9 research has focused primarily on mammals, and its role in recombination localization has only recently been established in salmonids. PRDM9 binding specificity is determined by a tandemly repeated zinc-finger array that exhibits extensive allelic diversity within and between species. However, the extent to which PRDM9 variation shapes recombination landscapes in salmonids remains poorly understood. Here, we performed large-scale genotyping of PRDM9 in an aquaculture population of Atlantic salmon (Salmo salar) using long-read sequencing. By integrating PRDM9 genotypes with pedigree information and genome-wide recombination data, we generated PRDM9-specific linkage maps and sets of inferred crossover events. We show that the presence of specific PRDM9 alleles is associated with differences in recombination localization and identify patterns consistent with dominance interactions between alleles. Using population-averaged recombination rate estimates, we further link a previously described sequence motif enriched in European recombination hotspots to the presence of a common PRDM9 zinc-finger array allele (RPT6a). Together, our results demonstrate functional differences between PRDM9 alleles which contribute to divergence in recombination landscapes in Atlantic salmon, paralleling patterns observed in mammals. The broad geographic distribution of Atlantic salmon, combined with extensive pedigree data generated through aquaculture, highlights its potential as a powerful model for studying PRDM9 function and evolution beyond mammals.

genetics↗

bioRxiv2026

Transcriptomic view of key events during early embryogenesis in the duplicated Atlantic salmon genome

Early embryogenesis is governed by tightly regulated transcriptional programs, including the maternal-to-zygotic transition (MZT), zygotic genome activation (ZGA), and maintenance of pluripotency. While these processes are well studied in model vertebrates, they remain poorly understood in salmonid fishes, whose genomes are shaped by a relatively recent whole genome duplication (WGD) event. Here, we present a temporally resolved transcriptomic analysis of Atlantic salmon (Salmo salar) embryogenesis using bulk RNA-seq across key stages spanning early embryogenesis. Dimensionality reduction and unsupervised clustering of gene expression revealed stage-specific transitions encompassing maternal RNA clearance, cell cycle regulation, and the onset of metabolic activity. We demonstrate that ZGA occurs early and in multiple phases, beginning soon after fertilization, accompanied by chromatin remodelling and the activation of epigenetic regulators. Duplicated gene pairs retained from the salmonid WGD frequently displayed asynchronous expression, indicative of functional divergence and the evolution of additional regulatory complexity of embryonic development. To gain insights into pluripotency, we integrated analyses of gene expression, transcription factor motifs, and chromatin accessibility, to reveal conserved regulators including genes encoding Pou5f3, Nanog, and Sox19b, alongside divergent functions of Klf family members. Our cross-stage profiling allowed us to define a novel panel of stably-expressed reference genes for normalization during quantitative PCR analyses, which were used to validate pluripotency- and differentiation-associated dynamics inferred by RNA-seq. Together, our findings delineate the transcriptional architecture of early embryogenesis in Atlantic salmon, revealing both conserved and lineage-specific features of pluripotency regulation, and providing a foundational resource for future functional genomics and stem cell applications in salmonids.

developmental biology↗

bioRxiv2026

A gapless Landrace pig genome resolves centromeres and telomeres and highlights telomere repeat structures in different pig breeds

The Duroc-derived reference genome Sscrofa11.1 has provided a critical foundation for pig genomics, providing a high-quality reference genome for accurate variant detection and comparative genomics but does not capture breed-specific variation. Here, we present a near-complete, gap-free genome assembly for the Landrace pig (Landrace_v1, GCA_963921485.1), spanning all 20 chromosomes and totaling 2.6 Gb, including 176 Mb of sequence absent from Sscrofa11.1. Comparative analyses with recently published high-quality pig genomes reveal a conserved centromere organization across breeds, accompanied by substantial variation in repeat composition and length, and identify a pig specific pattern of telomere variant repeats across eight pig breeds. The improved resolution of repetitive regions in Landrace_v1 enables more complete reconstruction of complex gene families, including olfactory receptors, and uncovers structural variation at the KIT proto-oncogene receptor tyrosine kinase locus not represented in the Duroc reference. Together, these findings highlight the limitations of single-reference genomes and demonstrate the value of breed-specific assemblies for capturing genomic diversity and improving downstream analyses.

genomics↗

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 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

Large haplotypes linked to climate and life history variation in divergent lineages of Atlantic salmon (Salmo salar)

Advances in sequencing are revealing that linked genomic architectures, enabling the evolution of co-adapted alleles at multiple loci, often shape complex phenotypes. Several recent studies have identified such architectures (e.g., chromosomal rearrangements and supergenes) contributing to adaptation or divergence across diverse species, from plants to mammals. Specifically, within Atlantic salmon (Salmo salar), genomic studies are revealing large haplotypes and structural variants that may underpin local adaptation in the species. Using data from >4000 individuals from 134 locations spanning the North Atlantic Ocean, we identify a large ([~]3-Mbp) genomic region on Ssa18 showing patterns of differentiation and linkage disequilibrium indicative of a large haplotype block containing three divergent haplotypes (herein A, B, and C haplotypes). In Europe, haplotypes A and B were common, whereas A and C were more common within North America, suggesting a shared ancestral A haplotype, with different continent-specific alternative haplotypes. Data support independent origins of divergent haplotypes in each continent, as well as signals of trans-oceanic introgression of haplotypes. Haplotype frequency is strongly associated with latitude, climate, and life history (smolt age); however, the strength and direction of these relationships vary across continents. Overall analyses were consistent with other studies that identify chromosomal rearrangements; however, long read sequence data could not confirm evidence of a structural variant, although an ancestral fusion polymorphism may explain the formation and maintenance of the observed haplotypes. Our study contributes to ongoing efforts to understand the evolutionary role of linked genomic architecture in Atlantic salmon and its significance in salmonid diversification.

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↗

bioRxiv2023

Investigating structural variant, indel and single nucleotide polymorphism differentiation between locally adapted Atlantic salmon populations using whole genome sequencing and a hybrid genomic polymorphism detection approach

Genomic structural variants (SVs) are now recognized as an integral component of intraspecific polymorphism and are known to contribute to evolutionary processes in various organisms. However, they are inherently difficult to detect and genotype from readily available short-read sequencing data, and therefore remain poorly documented in wild populations. Salmonid species displaying strong interpopulation variability in both life history traits and habitat characteristics, such as Atlantic salmon (Salmo salar), offer a prime context for studying adaptive polymorphism, but the contribution of SVs to fine-scale local adaptation has yet to be explored. Here, we performed a comparative analysis of SVs, single nucleotide polymorphisms (SNPs) and small indels (< 50 bp) segregating in the Romaine and Puyjalon salmon, two putatively locally adapted populations inhabiting neighboring rivers (Quebec, Canada) and showing pronounced variation in life history traits, namely growth, fecundity, and age at maturity and at smoltification. We first catalogued polymorphism using a hybrid SV characterization approach pairing both short (16X) and long-read sequencing (20X) for variant discovery with graph-based genotyping of SVs across 60 salmon genomes, along with characterization of SNPs and small indels from short reads. We thus identified 115,907 SVs, 8,777,832 SNPs and 1,089,321 short indels, with SVs covering 4.8 times more base pairs than SNPs. All three variant types revealed a highly congruent population structure and similar patterns of FSTand density variation along the genome. Finally, we performed outlier detection and redundancy analysis (RDA) to identify variants of interest in the putative local adaptation of Romaine and Puyjalon salmon. Genes located near these variants were enriched for biological processes related to nervous system function, suggesting that observed variation in traits such as age at smoltification could arise from differences in neural development. This study therefore demonstrates the feasibility of large-scale SV characterization and highlights its relevance for salmonid population genomics.

genomics↗

bioRxiv2022

Genome assembly, structural variants, and genetic differentiation between Lake Whitefish young species pairs (Coregonus sp.) with long and short reads

Nascent pairs of ecologically differentiated species offer an opportunity to get a better glimpse at the genetic architecture of speciation. Of particular interest is our recent ability to consider a wider range of genomic variants, not only single-nucleotide polymorphisms (SNPs), thanks to long-read sequencing technology. We can now identify structural variants (SVs) like insertions, deletions, and other rearrangements, allowing further insights into the genetic architecture of speciation and how different types of variants are involved in species differentiation. Here, we investigated genomic patterns of differentiation between sympatric species pairs (Dwarf and Normal) belonging to the Lake Whitefish (Coregonus clupeaformis) species complex. We assembled the first reference genomes for both C. clupeaformis sp. Normal and C. clupeaformis sp. Dwarf, annotated the transposable elements, and analysed the genomes in the light of related coregonid species. Next, we used a combination of long-read and short-read sequencing to characterize SVs and genotype them at population-scale using genome-graph approaches, showing that SVs cover five times more of the genome than SNPs. We then integrated both SNPs and SVs to investigate the genetic architecture of species differentiation in two different lakes and highlighted an excess of shared outliers of differentiation. In particular, a large fraction of SVs differentiating the two species correspond to insertions or deletions of transposable elements (TEs), suggesting that TE accumulation may represent a key component of genetic divergence between the Dwarf and Normal species. Altogether, our results suggest that SVs may play an important role in speciation and that, by combining second and third generation sequencing, we now have the ability to integrate SVs into speciation genomics.

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↗

bioRxiv2021

Dissecting the loci underlying maturation timing in Atlantic salmon using haplotype and multi-SNP based association methods

Resolving the genetic architecture of fitness-related traits is key to understanding the evolution and maintenance of fitness variation. However, well-characterized genetic architectures of such traits in wild populations remain uncommon. In this study, we used haplotype-based and multi-SNP Bayesian association methods with sequencing data for 313 individuals from wild populations to further characterize known candidate regions for sea age at maturation in Atlantic salmon (Salmo salar). We detected an association at five loci (on chromosomes ssa06, ssa09, ssa21, and ssa25) out of 116 candidates previously identified in an aquaculture strain with maturation timing in wild Atlantic salmon. We found that at each of these five loci, variation explained by the locus was predominantly driven by a single SNP suggesting the genetic architecture of Atlantic salmon maturation includes multiple loci with simple, non-clustered alleles. This highlights the diversity of genetic architectures that can exist for fitness-related traits. Furthermore, this study provides a useful multi-SNP framework for future work using sequencing data to characterize genetic variation underlying phenotypes in wild populations.

evolutionary biology↗

bioRxiv2021

The salmon louse genome: copepod features and parasitic adaptations.

Copepods encompass a range of ecological roles from parasites to phytoplankton grazers linking primary producers to higher trophic levels. Despite these important roles, copepod genome assemblies are scarce. Lepeophtheirus salmonis is an economically and ecologically important ectoparasitic copepod. We present the 695.4 Mbp L. salmonis genome assembly containing {approx}60% repetitive regions and 13081 annotated protein-coding genes. The genome comprises 14 autosomes and a ZZ-ZW sex chromosome system. Assembly assessment identified 92.4% of the expected arthropod genes. Transcriptomics validated annotation and revealed a marked shift in gene expression after host attachment, including downregulation of genes related to circadian rhythm coinciding with abandoning diurnal migration. The genome shows evolutionary signatures including loss of peroxisomes, numerous FNII domains, and an incomplete heme homeostasis pathway suggesting heme proteins to be obtained from the host. Despite large capacity to develop resistance against chemical treatments L. salmonis exhibits low numbers of many genes involved in detoxification.

genomics↗

bioRxiv2020

The structural variation landscape in 492 Atlantic salmon genomes

Structural variants (SVs) are a major source of genetic and phenotypic variation, but remain challenging to accurately type and are hence poorly characterized in most species. We present an approach for reliable SV discovery in non-model species using whole genome sequencing and report 15,483 high-confidence SVs in 492 Atlantic salmon (Salmo salar L.) sampled from a broad phylogeographic distribution. These SVs recover population genetic structure with high resolution, include an active DNA transposon, widely affect functional features, and overlap more duplicated genes retained from an ancestral salmonid autotetraploidization event than expected. Changes in SV allele frequency between wild and farmed fish indicate polygenic selection on behavioural traits during domestication, targeting brain-expressed synaptic networks linked to neurological disorders in humans. This study offers novel insights into the role of SVs in genome evolution and the genetic architecture of domestication traits, along with resources supporting reliable SV discovery in non-model species.

genomics↗

bioRxiv2019

A nanopore based chromosome-level assembly representing Atlantic cod from the Celtic Sea.

Currently available genome assemblies for Atlantic cod (Gadus morhua) have been constructed using DNA from fish belonging to the Northeast Arctic Cod (NEAC) population; a migratory population feeding in the cold Barents Sea. These assemblies have been crucial for the development of genetic markers which have been used to study population differentiation and adaptive evolution in Atlantic cod, pinpointing four discrete islands of genomic divergence located on linkage groups 1, 2, 7 and 12. In this paper, we present a high-quality reference genome from a male Atlantic cod representing a southern population inhabiting the Celtic sea. Structurally, the genome assembly (gadMor_Celtic) was produced from long-read nanopore data and has a combined contig size of 686 Mb with a N50 of 10 Mb. Integrating contigs with genetic linkage mapping information enabled us to construct 23 chromosome sequences which mapped with high confidence to the latest NEAC population assembly (gadMor3) and allowed us to characterize in detail large chromosomal inversions on linkage groups 1, 2, 7 and 12. In most cases, inversion breakpoints could be located within single nanopore contigs. Our results suggest the presence of inversions in Celtic cod on linkage groups 6, 11 and 21, although these remain to be confirmed. Further, we identified a specific repetitive element that is relatively enriched at predicted centromeric regions. Our gadMor_Celtic assembly provides a resource representing a southern cod population which is complementary to the existing northern population based genome assemblies and represents the first step towards developing pan-genomic resources for Atlantic cod.

genomics↗

bioRxiv2019

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, several 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.

genomics↗

bioRxiv2018

Sex-dependent dominance maintains migration supergene in rainbow trout

Traits with different fitness optima in males and females cause sexual conflict when they have a shared genetic basis. Heteromorphic sex chromosomes can resolve this conflict and protect sexually antagonistic polymorphisms but accumulate deleterious mutations. However, many taxa lack differentiated sex chromosomes, and how sexual conflict is resolved in these species is largely unknown. Here we present a chromosome-anchored genome assembly for rainbow trout (Oncorhynchus mykiss) and characterize a 56 Mb double-inversion supergene that mediates sex-specific migration through sex-dependent dominance, a mechanism that reduces sexual conflict. The double-inversion contains key photosensory, circadian rhythm, adiposity, and sexual differentiation genes and displays frequency clines associated with latitude and temperature, revealing environmental dependence. Our results constitute the first example of sex-dependent dominance across a large autosomal supergene, a novel mechanism for sexual conflict resolution capable of protecting polygenic sexually antagonistic variation while avoiding the homozygous lethality and deleterious mutation load of heteromorphic sex chromosomes.

evolutionary biology↗

bioRxiv2018

Chromosome-scale assemblies reveal the structural evolution of African cichlid genomes

BackgroundAfrican cichlid fishes are well known for their rapid radiations and are a model system for studying evolutionary processes. Here we compare multiple, high-quality, chromosome-scale genome assemblies to understand the genetic mechanisms underlying cichlid diversification and study how genome structure evolves in rapidly radiating lineages.\n\nResultsWe re-anchored our recent assembly of the Nile tilapia (Oreochromis niloticus) genome using a new high-density genetic map. We developed a new de novo genome assembly of the Lake Malawi cichlid, Metriaclima zebra, using high-coverage PacBio sequencing, and anchored contigs to linkage groups (LGs) using four different genetic maps. These new anchored assemblies allow the first chromosome-scale comparisons of African cichlid genomes.\n\nLarge intra-chromosomal structural differences (~2-28Mbp) among species are common, while inter-chromosomal differences are rare (< 10Mbp total). Placement of the centromeres within chromosome-scale assemblies identifies large structural differences that explain many of the karyotype differences among species. Structural differences are also associated with unique patterns of recombination on sex chromosomes. Structural differences on LG9, LG11 and LG20 are associated with reductions in recombination, indicative of inversions between the rock- and sand-dwelling clades of Lake Malawi cichlids. M. zebra has a larger number of recent transposable element (TE) insertions compared to O. niloticus, suggesting that several TE families have a higher rate of insertion in the haplochromine cichlid lineage.\n\nConclusionThis study identifies novel structural variation among East African cichlid genomes and provides a new set of genomic resources to support research on the mechanisms driving cichlid adaptation and speciation.

genomics↗

bioRxiv2018

A migration-associated supergene reveals loss of biocomplexity in Atlantic cod

Intraspecific phenotypic diversity is integral to ecological resilience and the provision of ecosystem services1. Chromosome structural variation may underpin intraspecific diversity and complex phenotypes2 by reducing recombination within supergenes containing linked, co-adapted alleles. Connecting ecologically-relevant phenotypes to genomic variation can enable more precise conservation of exploited marine species by protecting important genetic diversity3,4. Here, using genome-wide association analysis of a 12K single nucleotide polymorphism (SNP) array we confirm that an ancient, derived chromosomal rearrangement consisting of two adjacent inversions is strongly associated with migratory phenotype and individual-level genetic structure in Atlantic cod (Gadus morhua) across the Northwest Atlantic. The presence of all identified migration-associated loci within this rearrangement indicates that pervasive variation in migration phenotype is in part controlled by a recombination-resistant supergene, facilitating fine-scale individual phenotypic variation within Northern cod. Furthermore, we reconstruct trends in effective population size over the last century, and find genomic signatures of population collapse, and different patterns of population expansion and decline among individuals based on supergene alleles. We demonstrate declines in effective population size consistent with the onset of industrialized harvest (post 1950) and substantially reduced effective size of individuals homozygous for the derived chromosomal rearrangement relative to heterozygous individuals or those homozygous for the ancestral version of this chromosomal region. These results illustrate how chromosomal structural diversity can mediate fine-scale genetic and phenotypic variation in a highly connected marine species, and suggest a loss of biocomplexity from a migration-associated supergene within Northern cod by overfishing.

genomics↗