Girardi, M. | bioRxiv Science

bioRxiv2026

Misleading Success: Genomes Reveal Critical Risks to European Gray Wolves

Have European gray wolves recovered? Despite an increase to [~]21,000 wolves (Canis lupus), our genomic analyses reveal significant risks to their long-term viability. We analyzed over 200 whole-genomes spanning five major European populations. Rather than a single recovering population, European wolves form a mosaic of isolated, independently evolving lineages, mostly diverging in the late Pleistocene. All lineages have contemporary effective population sizes below the threshold for long-term viability (Ne [≥] 500) and show extensive inbreeding. Runs of homozygosity reveal population-specific inbreeding histories spanning recent to deep timeframes. Most lineages exhibit higher realized than masked genetic load, indicating emerging inbreeding depression. These findings challenge claims that downlisting European wolves is biologically warranted: none of these populations currently meets thresholds associated with favorable conservation status.

evolutionary biology↗

bioRxiv2024

Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4x10-9 per nt, we report that sun exposure creates pervasive mutations at sites with [~]100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3x10-5 per nt. Clonal expansion by neutral drift or passenger formation was nil. Tumor suppressor gene hotspots reached variant allele frequency 0.1-10% via 30-3,000 fold clonal expansion, in occasional biopsies. CPD hyperhotspots reached those frequencies in every biopsy, with modest clonal expansion. In vitro, tumor hotspot mutations arose occasionally over weeks of chronic low-dose exposure, whereas CPD hyperhotspot mutations arose in days at 1000-fold higher frequencies, growing exponentially. UV targeted mini-drivers in every skin cell.

genomics↗