From folklore to explore: integrating genomic and multi-omics data for <i>Clinacanthus nutans</i> provides insights into the evolution and organ-specific therapeutic basis

Abstract Clinacanthus nutans is a traditional medicinal plant widely used in Southeast Asia for treating inflammation, viral infections, and cancer. However, its molecular basis remains poorly understood. In this study, the first chromosome-scale genome of C. nutans (731.61 Mbp) was assembled, with 93.76% anchored to 18 pseudochromosomes. Repetitive elements constituted 69.05% of the genome, predominantly long terminal repeat (LTR) retrotransposons. Phylogenomic and synonymous substitution rate (Ks) analyses revealed a Lamiales-wide whole-genome duplication (WGD) event, followed by extensive chromosomal rearrangements. Gene family expansion analysis showed that segmental and dispersed duplications were the primary drivers of enzyme-coding genes (EGs) expansion involved in the flavonoid and triterpenoid pathways. Integrated transcriptomic and metabolomic analyses across five organs revealed distinct organ-specific expression and metabolite profiles. Genes exhibited pronounced differential expression between leaves and roots, with enrichment in flavonoid and triterpenoid biosynthetic pathways, highlighting functional divergence and metabolic specialization. Flavonoids were enriched in aerial tissues, whereas triterpenoids accumulated in roots. Weighted gene co-expression network analysis (WGCNA) identified key EGs (e.g., CHS, CHI, OSC) and core transcription factors (TFs) (e.g., MYB, bHLH, WRKY) potentially involved in organ-specific metabolic regulation. These findings suggest a coordinated transcriptional-metabolic regulatory framework underlying the specialized functions of different tissues. This work provides valuable genomic resources and mechanistic insights into the biosynthesis and regulation of bioactive compounds in C. nutans, thereby facilitating future research and molecular breeding of this important ethnomedicinal plant.