From gene clusters to medicine: researchers decode the full genome of Centella asiatica
image: T2T wild C. asiatica genome. A. Phenotypic characteristics of different tissues of wild C. asiatica. All genomic data in our study were derived from leaves, while transcriptomic data were obtained from roots, stems, and leaves. B. Gene density and the distribution of telomeres and centromeres of C. asiatica genome. C. Genome characteristics of C. asiatica. The quantitative tracks are aggregated in 500-kb bins and the tracks from outside to inside are shown as follows: pseudochromosomes (Chr1 to Chr9), gene density, TE density, Gypsy LTR density, Copia LTR density, GC content, and chromosomal collinearity. D. Hi-C interaction matrix (100-kb resolution), A/B compartments (PCA score), gene density, TE density, and gene expression throughout chromosome 9. The Hi-C and RNA-seq data were derived from leaf tissues. E. Representative TAD structures in chromosome 9. . The 5-kb resolution was used for drawing Hi-C contact heatmap. F. Size distributions of topologically associated domains in the whole genome.
Credit: Horticulture Research
Centella asiatica, also known as gotu kola, is widely valued for its triterpenoid saponins, especially asiaticoside and madecassoside, which are used in pharmaceuticals, skincare, and neurological health supplements. However, the lack of a complete genome has limited understanding of how these compounds are synthesized and regulated. This study presents the first telomere-to-telomere (T2T) genome of C. asiatica, revealing its evolutionary history and identifying specialized gene clusters and regulatory mechanisms that control triterpenoid saponin biosynthesis. The integration of genome sequencing, 3D chromatin architecture mapping, and expression profiling uncovered key biosynthetic genes and transcriptional regulation patterns essential for metabolite production.
Triterpenoid saponins such as asiaticoside and madecassoside are pharmacologically active compounds with wound-healing, anti-inflammatory, neuroprotective, and cosmetic benefits. Their biosynthesis involves multiple enzymatic steps, including skeleton formation by oxidosqualene cyclases (OSCs), oxidation by cytochrome P450 enzymes (CYPs), and glycosylation by UDP-glycosyltransferases (UGTs). While these pathways have been partially explored in plants, the genomic organization, evolutionary origin, and regulatory mechanisms of these biosynthetic genes in C. asiatica have remained unclear. Due to these challenges, there is a need to conduct an in-depth study that links genome structure, metabolic evolution, and gene regulation in C. asiatica.
Researchers from Yunnan Agricultural University and collaborating institutions published (DOI: 10.1093/hr/uhaf037) their findings on May 1, 2025, in Horticulture Research. The team generated a complete telomere-to-telomere (T2T) genome assembly of C. asiatica and constructed its three-dimensional chromatin architecture to uncover how genome organization influences triterpenoid biosynthesis. They further identified key gene clusters and regulatory networks involved in the production of asiaticoside and madecassoside, offering new insights into the genetic basis of this medicinal plant’s bioactivity.
The researchers assembled a 438 Mb high-quality genome containing 25,200 protein-coding genes. Comparative genomics revealed that C. asiatica diverged early within the Apiaceae family and experienced only one ancient whole-genome duplication event, unlike most Apiaceae species which experienced two. This unique evolutionary path contributed to specialized triterpenoid biosynthetic capacity. The study identified CasiOSC03 as the key oxidosqualene cyclase responsible for forming the α-amyrin backbone. Expansion of CYP716 and CYP714 gene families was linked to hydroxylation steps that define asiaticoside structure. Moreover, a large tandem gene cluster of the UGT73 family was discovered within the same topologically associated domain (TAD), indicating coordinated transcriptional regulation to enhance glycosylation potential. Hi-C mapping showed that the spatial genome architecture promotes the expression of biosynthetic genes by maintaining them in active chromatin compartments. Methyl jasmonate response experiments demonstrated strong transcriptional activation of CasiOSC03, CYP716C11, CYP714E19, and UGT73AD1, confirming their involvement in inducible saponin biosynthesis. Together, these findings reveal an integrated evolutionary and regulatory framework controlling triterpenoid production.
“Our findings provide the most complete genomic and regulatory map available for C. asiatica,” said the study’s corresponding authors. “By showing how gene duplication, chromatin structure, and metabolic pathway organization come together to shape the biosynthesis of asiaticoside and madecassoside, this work establishes a foundation for metabolic engineering. It opens new possibilities for improving the yield and diversity of bioactive saponins in medicinal and agricultural applications.”
The complete genome and regulatory insights from this study will enable molecular breeding, synthetic biology, and precision cultivation strategies aimed at increasing asiaticoside and madecassoside production. Understanding gene cluster regulation and 3D chromatin structure further provides targets for CRISPR editing and metabolic enhancement. These advances offer significant potential for pharmaceutical development, regenerative medicine, and high-value botanical product industries. Overall, the research provides both scientific insight and practical pathways toward improved utilization of C. asiatica as a medicinal resource.
###
References
DOI
Original Source URL
https://doi.org/10.1093/hr/uhaf037
Funding information
This work was supported by the Yunnan Characteristic Plant Extraction Laboratory (2022YKZY001) and Yunnan Seed Laboratory (202305AR340004).
About Horticulture Research
Horticulture Research is an open access journal of Nanjing Agricultural University and ranked number one in the Horticulture category of the Journal Citation Reports ™ from Clarivate, 2023. The journal is committed to publishing original research articles, reviews, perspectives, comments, correspondence articles and letters to the editor related to all major horticultural plants and disciplines, including biotechnology, breeding, cellular and molecular biology, evolution, genetics, inter-species interactions, physiology, and the origination and domestication of crops.