Biology subjects

Frapin, M.

Publications and source records attributed to Frapin, M..

9 recordsLinked to original sources

bioRxiv2026

A major life-history locus underlies genotype-by-environment variation in growth across water temperatures

Rapid environmental change is exposing organisms to conditions that do not match those under which they evolved, making it increasingly important to understand how genetic variation shapes phenotypic responses to environmental stress. Since most phenotypic traits arise from interactions between genetic variation and the environments experienced throughout an organisms lifetime, understanding the genetic architecture of these interactions is central to predicting how populations will respond to novel environments. While genotype-by-environment interactions (GxE) are well studied in quantitative genetics, identifying specific loci that contribute to environmentally dependent trait expression remains rare. Salmonids already exhibit a wide portfolio of plastic life-history strategies, reflecting adaptation to highly heterogeneous environments, yet it remains unclear whether known major-effect loci involved in life-history regulation also contribute to variation in plastic responses to environmental change. One such major-effect locus is the transcription factor six6, which has been repeatedly associated with variation in age at maturity across multiple populations of rainbow trout (Oncorhynchus mykiss). Since maturation timing is closely linked to growth trajectories and patterns of energetic allocation during early development, allelic variation at this locus may also influence growth responses to warming conditions. Here, we test this hypothesis using a common-garden experiment in which 6 months old juvenile rainbow trout were reared under current and warming (+2{degrees}C) temperature regimes. By quantifying genotype-specific reaction norms across environments, we show that six6 genotype contributes to environmentally dependent variation in growth and body composition, with individuals heterozygous for the six6 locus showing a distinct and steeper response to warming relative to homozygotes. These findings provide evidence that a major life-history gene shapes plastic responses to thermal stress in juvenile rainbow trout, with novel implications for how standing genetic variation at in large-effect loci may influence population-level responses to climate warming.

evolutionary biology↗

bioRxiv2025

Maternal protein restriction alters chromatin accessibility in neuroprogenitors of the fetal hypothalamus of rats.

Maternal protein restriction (PR) is a risk factor for altered fetal neurodevelopment and an increased susceptibility to neurometabolic disorders later in life. Although structural and transcriptomic changes in the developing hypothalamus have been reported in PR-exposed offspring, the underlying regulatory mechanisms remain unclear. We hypothesized that maternal PR alters chromatin accessibility in hypothalamic neuroprogenitor cells, thereby disrupting gene regulation critical for cell fate specification. We performed ATAC-seq on hypothalamic neuroprogenitors isolated at gestational day 17 from rat fetuses that were exposed to an isocaloric PR diet. We identified 312 differentially accessible chromatin regions, including reduced accessibility near genes encoding Major Histocompatibility Complex class I (MHC-I) proteins, amino acid transporters and proteins involved in neuronal differentiation and synaptic signaling. Motif enrichment analysis revealed reduced accessibility at FOS/JUN and DBP binding sites in PR samples, alongside enrichment of Kruppel-like transcription factor motifs in more accessible regions. RNA-seq on neurospheres generated from these progenitors identified 91 differentially expressed genes, enriched in pathways related to cell proliferation, protein-lipid metabolism, and apoptosis. Mapping these genes onto previously generated single-cell RNA-seq data associated several of them with specific neuroprogenitor subpopulations. With the exception of two genes (RT1-A2 and Nav2), the differential ATAC-seq peaks did not correspond to a statistically significant difference in neighboring gene expression levels. Our preliminary findings suggest that maternal PR alters the chromatin landscape of fetal hypothalamic progenitors, potentially disrupting key developmental trajectories, representing a mechanism of fetal programming of metabolic dysfunction.

developmental biology↗

bioRxiv2025

A Comprehensive Analysis of Atlantic Salmon Gonad and Pituitary Transcriptomes Identifies Novel Players in Sexual Maturation

BackgroundSexual maturation is a key developmental process important for reproductive success. Understanding the molecular mechanisms behind variation in sexual maturation can provide insights into reproductive biology and how life history variation is encoded in the genome. Atlantic salmon (Salmo salar) has become an excellent sexual maturation research model due to its diversity of life history strategies and its ecological and economic importance. A major challenge has been the lack of a comprehensive transcriptional investigation of reproductive tissues that captures the dynamic transcriptional changes across individuals, tissues, and developmental stages. Long non-coding RNAs (lncRNAs) also play crucial roles in maturation, yet their functions in salmon maturation remain underexplored. ResultsIn this study, we sequenced 98 transcriptomes and found substantial transcriptomic complexity in the gonad and pituitary tissues of Atlantic salmon. We identified transcripts corresponding to 2,364 putative newly characterized protein-coding genes and 4,421 putative long intergenic non-coding RNAs (lincRNAs), many with tissue-specific expression. Gene co-expression network analysis (WGCNA) revealed tissue-specific gene network modules, linked to GO terms including Wnt signaling in immature testis, lipid metabolism, and cilia assembly in mature testis, ribosome biogenesis and DNA repair in the ovary, and hormone activity in pituitary. We identified new copies of known genes, such as gh1, pou3f2, and ier5 associated with the regulation of gonadal and pituitary functions. Some lncRNAs and their nearest genes showed correlated expression within modules, suggesting potential regulatory roles. Candidate lincRNAs indicated cis-acting regulatory potential on genes like tnfrsf11b and fgl1, which are implicated in immune privilege during gonadal development and sperm quality control. ConclusionsOur study provides a comprehensive transcriptomic analysis of Atlantic salmon gonad and pituitary tissues, significantly improving the functional annotation of the Atlantic salmon genome. These findings reveal key regulatory pathways and novel molecular players involved in sexual maturation, particularly in the testis. Importantly, our study highlights the regulatory potential of lncRNAs in reproductive biology and maturation age variation, advancing our understanding of the molecular mechanisms governing sexual maturation. They further unlock future gene expression analyses and regulatory network reconstruction for dissecting the roles of lncRNAs in Atlantic salmon life history variation.

genetics↗

bioRxiv2025

Maternal low protein diet alters the development of reward circuits from childhood to adulthood by reshaping its function

Inadequate nutrition during pregnancy can lead to intrauterine growth retardation and low birth weight, which in turn increases the risk of developing metabolic disorders in adulthood, according to various epidemiological and clinical studies. The inclination of individuals born with low birth weight towards palatable foods indicates a possible modification in the hedonic aspect of their eating behavior. However, our understanding of the ontogenesis of structural organization and function within the brains reward circuits remains limited. Therefore, the objective of this research is to investigate the preferences for palatable food, molecular signatures of reward circuits, and functional properties of the nucleus accumbens (NAc) in a rat model of perinatal protein restriction (LP). Starting from weaning, continuing into adolescence and adulthood, a longitudinal analysis was conducted on rats born to mothers with protein-restricted diets during gestation and lactation (LP pups), comparing them to pups born from control dams (CD pups). The LP group exhibited an increased preference for palatable food at day 25 after birth (P25), followed by a decreased preference during adolescence (P50), and no significant difference in palatable food preference at P95 (young adult) compared to CD rats. Molecular and electrophysiological assessments of medium spiny neurons (MSN) in the NAc revealed a reorganization of reward circuits during crucial developmental periods, potentially influencing the attractiveness of palatable food for the LP group. This study represents the first exploration of how preferences for palatable food evolve throughout an individuals lifespan and how these observations correlate with the remodeling of reward circuits. By shedding light on the molecular and functional aspects of reward circuits, we contribute to a better understanding of the link between perinatal nutrition, behavioral preferences, and the underlying neural mechanisms.

neuroscience↗

bioRxiv2025

Density-dependent expression of epitranscriptomic, stress, and appetite regulating genes in Atlantic salmon

Intraspecific competition due to e.g., density, has substantial influence on fitness dynamics and life histories, but the underlying physiological mechanisms are often complex, and the molecular basis unclear. Further, designing laboratory experiments to measure physiological responses that reflect natural conditions is challenging. Here, we reared Atlantic salmon juveniles in semi-wild conditions in two naturally occurring densities to investigate the molecular mechanism of density-related changes in the hypothalamus, a key brain region regulating stress and energy homeostasis. We measured density-dependent changes in the expression of 12 genes involved in appetite and stress regulation, and 16 genes involved in post-transcriptional regulation of gene expression via m6A RNA methylation. This gene set includes paralog pairs, to account for potential functional divergence associated with salmonid genome duplication. We also quantified genotype-environment interactions between density and two major life-history loci, vgll3 and six6. We found significant density-related differences in the expression of genes coding for corticotropin-releasing factors, appetite stimulators and inhibitors, and m6A RNA methylation actors. Moreover, a paralogue of an appetite inhibitor showed a density-dependent pattern that was the opposite of what was expected. Six6 locus was also associated with changes in the expression of epitranscriptomic markers, including two writers and one eraser. Our results highlight that individuals response to density in natural conditions is shaped by a complex interplay between stress, appetite and epitranscriptomic pathways in the hypothalamus. In addition, the functional divergence of paralogs indicates a potential role of genome duplication shaping such a response. We emphasize the value of integrating different physiological responses at the molecular level to better understand ecological processes affected by environmental change.

molecular biology↗

bioRxiv2024

Sex-, development-, and nutrition-dependent expression of a major age-at-maturity gene in Atlantic salmon

Sexual maturation is a key process in the life history of an organism and is influenced by both genetic and environmental factors. In Atlantic salmon (Salmo salar), alternative alleles at the gene vgll3 have been found to associate with a large proportion of the variation in maturation age, yet the molecular and physiological mechanisms of this association are still largely unknown. Here, we investigated the mechanisms by which genetic variation in this major age-at-maturity gene translated into phenotypic variation. We established a time series of gonadal vgll3 mRNA expression in male and female Atlantic salmon in a common garden setting, starting at the prepubertal stage and spanning multiple spawning seasons. We found that vgll3 mRNA expression is reduced in early-maturing males and females. However, for the second spawning season, vgll3 expression increased with gonadal development in males, but eventually decreased in females. Expression of vgll3 had context-dependent correlations with expression of amh and lhr. We also found signs of reduced testicular vgll3 expression in a low-fat feed treatment. By significantly widening the scope of our knowledge on temporal vgll3 expression dynamics, our results exemplify that major-effect genes may use different pathways in sexes but achieve similar outcomes.

genetics↗

bioRxiv2024

A complex mechanism translating variation of a simple genetic architecture into alternative life-histories

Linking genes to traits is a central goal in biology. Despite progress in discovering genes associated with trait differences, a poor understanding of the functional mechanisms underlying genetic associations leaves us critically far from connecting genetic and phenotypic variation. This knowledge-gap is particularly large in multifaceted phenotypes of ecological relevance such as life-history traits. Using a multiomic dissection of the genotype-phenotype association in a large-effect maturation age gene - the transcription cofactor vestigial-like 3 (vgll3) - in Atlantic salmon (Salmo salar), we show that vgll3 mediates concerted changes of distinct molecular phenotypes associated with puberty in male gonads. Vgll3 genotype conferring early maturity upregulates key genes controlling androgen production, cellular energy and adiposity, and TGF-{beta} signaling, among others, thereby increasing the likelihood of earlier pubertal initiation. Genotype-dependent developmental trajectories are produced through VGLL3 interaction with distinct transcription factors, thus coordinating differential activation of regulatory pathways. These results reveal a genetically simple, yet functionally complex, architecture underlying alternative life-histories where variation in a single major effect gene produces pleiotropic variation in a spectrum of cellular traits. Our results further suggest that evolution in correlated phenotypes such as exemplified by alternative life history strategies may be mediated by a surprisingly simple genetic architecture.

evolutionary biology↗

bioRxiv2023

Seasonal and genetic effects on lipid profiles of juvenile Atlantic salmon

Seasonality can influence many physiological traits requiring optimal energetic capacity for life-history stage transitions. In Atlantic salmon, high-energy status is essential for the initiation of maturation. Atlantic salmon lipid reserves are predominantly found in the viscera and myosepta in the muscle while the liver is essential for maintaining lipid metabolism. A genomic study found a region including a transcription co-factor-coding gene, vgll3, linked to Atlantic salmon maturation timing, which acts as an inhibitor of adipogenesis in mice, and mediates maturation via condition factor in Atlantic salmon. Here we investigate the influence of season and vgll3 genotypes associating with early (EE) and late (LL) maturation on lipid profiles in the muscle and liver in juvenile Atlantic salmon. We reared Atlantic salmon for two years until the occurrence of sexually mature males and sampled muscle and liver at two time points: spring and autumn of the second year. We found no seasonal or genotype effect in lipid profiles in muscle of immature males and females. However, in the liver we did detect a triacylglycerol (TG) enrichment and a genotype specific direction of change in membrane lipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), from spring to autumn. Specifically, from spring to autumn membrane lipid concentrations increased in vgll3*EE individuals and decreased in vgll3*LL individuals. This could be explained with two possible scenarios 1) a seasonally more stable capacity of endoplasmic reticulum (ER) functions in vgll3*EE individuals compared to vgll3*LL individuals or 2) vgll3*LL individuals storing larger lipid droplets from spring to autumn in the liver compared to vgll3*EE individuals at the expense of ER capacity. This genotype specific seasonal direction of change in membrane lipid concentrations provides more indirect evidence that a mechanism linking vgll3 with lipid metabolism and storage exists. HighlightsO_LISeasonal lipid species profile separation in muscle and liver in juvenile Atlantic salmon C_LIO_LIGenotype specific direction of change of membrane lipids from spring to autumn C_LIO_LIIndirect evidence that a mechanism linking vgll3 with lipid metabolism and storage exists C_LI

evolutionary biology↗

bioRxiv2022

Expression of m6A RNA methylation markers in the hypothalamus of Atlantic salmon

Methylation at the N6-position of adenosine, m6A, is the most abundant mRNA modification in eukaryotes. It is a highly conserved universal regulatory mechanism controlling gene expression in a myriad of biological processes. The role of m6A methylation in sexual maturation, however, has remained largely unexplored. While the maturation process is known to be affected by many genetic and environmental factors, the molecular mechanisms causing variation in the timing of maturation are still poorly understood. Hence, investigation of whether a widespread mechanism like m6A methylation could be involved in controlling of the maturation timing is warranted. In Atlantic salmon (Salmo salar), two genes associated with the age at maturity in human, vgll3 and six6, have been shown to play an important role in maturation timing. In this study, we investigated the expression of 16 genes involved in the regulation of m6A RNA methylation in the hypothalamus of Atlantic salmon with different homozygous combinations of late (L) and early (E) alleles for vgll3 and six6 genes. We found differential expression of ythdf2.2 which encodes an m6A modification reader and promotes mRNA degradation. Its expression was higher in six6*LL compared to other genotypes as well as immature males compared to matures. In addition, we found that the expression levels of genes coding for an eraser, alkbh5, and for a reader, ythdf1, were higher in the hypothalamus of females than in males across all the different genotypes studied. Our results indicate a potential role of the m6A methylation process in sexual maturation of Atlantic salmon, and therefore, provide the first evidence for such regulatory mechanism in the hypothalamus of any vertebrate. Investigation of additional vertebrate species is warranted in order to determine the generality of these findings.

molecular biology↗