Multi-omics insights into the woolly trait of Saussurea medusa and the plant’s coordinated regulation of flavonoid biosynthesis

The woolly plant Saussurea medusa is an endangered traditional Tibetan medicinal species and an ideal model to study high-altitude adaptation. Despite its ecological and pharmacological significance, the molecular mechanisms underlying its survival under harsh environments and its production of bioactive flavonoids remain poorly characterized. In this study, we assembled a high-quality chromosome-level genome of S. medusa (~3.8 Gb) with low heterozygosity and high repeat content. Comparative genomic analyses showed expansion of gene families related to DNA repair and hypoxia-adapted TCA cycle metabolism, and strong positive selection on light-harvesting complex pathways. Structural and functional analyses of the woolly trait demonstrated its roles in thermal insulation and light attenuation. Correspondingly, 48 key trichome-related genes were identified, reflecting a regulatory network dominated by the conserved GL1-GL3/(EGL3)-TTG1 transcriptional activator complex and linked to hormonal pathways. Metabolomics identified 1792 metabolites, including 18 bioactive metabolites with tissue-specific accumulation, most of which are flavonoids. Integrated metabolomics and transcriptomics analysis further revealed 27 flavonoid biosynthetic genes highly expressed in flowers and leaves, correlating strongly with the accumulation of flavonoids, indicating coordinated regulation of secondary metabolism. Our study provides multi-omic resources for S. medusa and provides insights into the genetic basis of its high-altitude adaptation, woolly trait, and medicinal properties.