Genetic mechanisms responsible for variations of ginsenosides content during the domestication of ginseng

Ginsenosides, the primary medicinally active substances in ginseng, are consistently used to treat a variety of diseases. Cultivated ginseng was domesticated from wild ginseng, but it was unclear whether the content of ginsenosides was modified and the underlying regulatory mechanisms during ginseng domestication. Here, we used transcriptome sequencing and metabolome analysis to compare of wild and cultivated accessions of ginseng to gain insight into the genetic and ginsenosides content changes associated with domestication. Genetic structure analysis revealed that ginseng might have undergone independent domestication in China and Korea, respectively, and a slightly reduced genetic diversity in wild and cultivated ginseng in China. Moreover, ginseng was domesticated approximately 1500 years ago in China, and a total of 330 genes was identified as signature of selective sweeps that occurred during ginseng domestication, including transcription factors (TFs) (MYB, bZIP, and GARP) and ginsenosides synthesis genes HMGCS058 and UGTs225. The total ginsenosides content was similar, but the content of numerous ginsenosides monomers differed significantly with wild ginseng compared to cultivated ginseng. Module-trait association analysis suggested abundant TFs highly associated with ginsenosides monomers content. In addition, a large number of ginsenosides synthesis genes were found to be subject to alternative splicing (AS) events. Together, our results suggested that that AS and TFs regulation contribute to the variation in ginsenosides content during domestication process. This study provided valuable genetic sources of ginsenosides that could contribute to ginseng breeding.