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 γ-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.