Biology subjects

de Coriolis, J.-C.

Publications and source records attributed to de Coriolis, J.-C..

4 recordsLinked to original sources

bioRxiv2026

Germline removal reprograms somatic genome maintenance towards faster, energy-efficient, high-fidelity DNA defence and repair

Germ cells maintain their genomes with greater fidelity than somatic cells, yet how germline status systemically shapes somatic genome protection in vertebrates remains poorly understood. Combining germline ablation with multi-organ transcriptomics in zebrafish (Danio rerio), we dissected germline control of somatic DNA repair and genotoxic stress responses. Using CRISPR/Cas9 mediated knockout of the germline determinant gene dnd-1, we compared germline free (GLF) males and germline carrying (GLC) siblings across five somatic organs at baseline and following sub-lethal {gamma}-irradiation, with sampling at 3 h and 24 h post-irradiation. Germline ablation profoundly reorganised baseline somatic transcription, favouring shorter, exon rich genes with functions in chromatin integrity, cell cycle control, and high-fidelity DNA repair, and attenuating DREAM complex repression of canonical repair targets. After irradiation, GLF fish mounted a faster response that rapidly engaged homologous recombination, checkpoint control, and proteostasis, whereas GLC fish remained biased toward biosynthetic and translational programmes. Hedgehog signalling acted as a transient regulatory node coordinating the strain-specific DNA damage response, and a repeat-rich region of chromosome 4 emerged as a hotspot of coordinated gene transposable element (TE) activity. GLF soma showed reduced early TE expression after irradiation, with LTR retrotransposons showing the strongest concordance with nearby differentially expressed genes. Our findings identify germline status as a systems level switch that tunes somatic genome maintenance and TE dynamics across multiple organs and provide a molecular framework for understanding how the germline regulates somatic ageing in vertebrates.

genetics↗

bioRxiv2025

Lifespan-extending downregulation of insulin signalling reduces germline mutation load

Reduced insulin/IGF-1 signalling (IIS) robustly extends lifespan and enhances somatic stress resistance across taxa, yet its consequences for germline genome integrity remain unclear. Here we combine multigenerational mutation accumulation with whole-genome sequencing in C. elegans to test whether adulthood-only IIS downregulation can simultaneously promote somatic maintenance and limit germline mutational burden. We reduced IIS by adult-onset daf-2 RNAi in wild-type and heritable RNAi-deficient (hrde-1) backgrounds, allowing either spontaneous or UV-induced germline mutations to accumulate over multiple generations. In wild-type animals, reduced IIS lowered germline single-nucleotide mutation rates by up to [~]50% and prevented the UV-induced elevation in mutation rate, without detectable costs to fecundity or lineage persistence. By contrast, in hrde-1 mutants the same intervention increased both point mutations and transposable-element-driven insertions under UV exposure, accelerating lineage extinction. Thus, the genome-protective effect of reduced IIS critically requires the germline nuclear Argonaute HRDE-1, which mediates small-RNA-guided epigenetic silencing. Functional annotation of germline variants revealed enrichment in pathways linked to development, cellular maintenance and conserved longevity regulators, including IIS and mTOR, and identified high-impact mutations in genes with human orthologs implicated in neurodegeneration and cancer. Our findings show that IIS can coordinate somatic and germline maintenance in concert, rather than in competition, through an HRDE-1-dependent epigenetic pathway. This work positions nutrient-sensing IIS as a central regulator of germline genome stability and suggests that IIS downregulation can reduce germline mutation load while extending lifespan, with broad implications for biogerontology and evolutionary biology.

evolutionary biology↗

bioRxiv2024

Gum Arabic (Acacia senegal) enhances reproduction and modulates the microbiota-gut-brain axis of zebrafish in a sex-specific and dosage-dependent manner

Dietary fibres (DFs) constitute a wide range of heterogeneous compounds that resist digestion and have beneficial effects on general health. Gum Arabic (GA) is a tree exudate consisting of 90% arabinogalactan, a polymer of arabinose and galactose sugars with prebiotic properties. As a dietary fibre, GA improves renal function, metabolism, and immune response in humans and animals. However, the underlying mechanisms leading to these health benefits are poorly understood. We supplemented female and male zebrafish (Danio rerio) with two concentrations of GA (6% and 60%) for two weeks. We assessed the effects of GA supplementation on the gut microbiome composition, intestinal and brain metabolic profiles, reproductive fitness, and brain gene expression. We found that GA supplementation resulted in changes to the gut microbiome with a relative increase in Fusobacteria and a relative decrease in Proteobacteria where the beneficial genus Cetobacterium was significantly more abundant after supplementation. GA supplementation increased acetate levels, particularly in the brain, causing a decreased expression of cart1 in the brain of female zebrafish. While GA supplementation increased overall activity in male and female fish, reproductive fitness was negatively affected by GA supplementation in females. Our results suggest that while GA supplementation may have positive effects on metabolic rate and overall activity, it may come at a trade-off with reproductive fitness. Significance StatementDietary fibres, found in plant-based food sources, can improve health. They include natural gums like gum Arabic, a highly sought-after food additive used as a homogeniser. Despite our better understanding of nutrition, a fibre gap is still prevalent in the Western world with efforts being made to incorporate new sources to close this gap and boost well-being. Here, we showed that when gum Arabic was supplemented into the zebrafish diet, it had a beneficial modulatory effect on the microbiota-gut-brain axis and reproductive fitness. Our findings support the benefits of dietary fibres but also link their impact to sexual dimorphism and dosage. This has implications for developing nutrition guidelines for both animals and humans.

systems biology↗

bioRxiv2022

Fasting increases investment in soma upon refeeding at the cost of gamete quality in zebrafish

Fasting increases lifespan in invertebrates, improves biomarkers of health in vertebrates, and is increasingly proposed as a promising route to improve human health. Nevertheless, little is known about how fasted animals use resources upon refeeding, and how such decisions affect putative trade-offs between somatic growth and repair, reproduction, and gamete quality. Such fasting-induced trade-offs are based on strong theoretical foundations and have been recently discovered in invertebrates, but the data on vertebrates is lacking. Here we report that fasted female zebrafish, Danio rerio, increase investment in soma upon refeeding but it comes at a cost of egg quality. Specifically, an increase in fin re-growth was accompanied by a reduction in 24-hours post-fertilization offspring survival. Refed males showed a reduction in sperm velocity and impaired 24-hour post-fertilisation offspring survival. These findings underscore the necessity of considering the impact on eggs and sperm when assessing evolutionary and biomedical implications of lifespan-extending treatments in females and males and call for careful evaluation of the effects of fasting (both during and post) on fertilisation.

evolutionary biology↗