Population genomics reveals ginseng domestication and ginsenoside biosynthesis

Ginseng (Panax ginseng), a valuable medicinal plant, is cultivated for the bioactive ginsenosides with cardiovascular protective effects that are abundant in its roots. However, the genetic basis of its domestication and ginsenoside variation is not fully understood. In this study, we resequenced 287 ginseng accessions and, through population genetic analyses, identified five clades associated with geographic regions and fruit color. Selective sweep analysis revealed genes related to adaptation and growth as well as triterpene biosynthesis. The profiling of 169 ginsenosides across these accessions revealed domestication-driven shifts in ginsenoside abundance between groups. A metabolite genome-wide association study identified 12,676 significant single nucleotide polymorphisms associated with ginsenosides. Based on these loci, we identified and functionally analyzed two key glycosyltransferases, PgUXT and PgURT, that govern xylosylation and rhamnosylation of polysaccharidic ginsenosides and significantly influence the accumulation of over half of the ginsenosides within the population. The genotype distribution of these two glycosyltransferases and their related ginsenoside divergence among the groups suggest that they are key candidate branch-point regulators for the population-level diversification of ginsenosides. Considering the identified genetic variants, we applied a machine learning-based genomic predictive model to predict ginsenoside abundance in individual plants for germplasm resource evaluation. Overall, this study elucidates the genomic foundations of domestication and ginsenoside diversification in ginseng and lays a foundation for the metabolite-directed improvement of this important medicinal plant.