Telomere-to-telomere genome assembly and 3D chromatin architecture of Centella asiatica insight into evolution and genetic basis of triterpenoid saponin biosynthesis

Abstract

Centella asiatica is renowned for its medicinal properties, particularly due to its triterpenoid saponins, such as asiaticoside and madecassoside, which are in excess demand for the cosmetic industry. However, comprehensive genomic resources for this species are lacking, which impedes the understanding of its biosynthetic pathways. Here, we report a telomere-to-telomere (T2T) C. asiatica genome. The genome size is 438.12 Mb with a contig N50 length of 54.12 Mb. The genome comprises 258.87 Mb of repetitive sequences and 25,200 protein-coding genes. Comparative genomic analyses revealed that C. asiatica as early diverging genus within the Apiaceae family with a single whole-genome duplication (WGD, Apiaceae-ω) event following the ancient γ-triplication, contrasting with Apiaceae species that exhibit two WGD events (Apiaceae-α and Apiaceae-ω). We further constructed 3D chromatin structures, A/B compartments and topologically associated domains (TAD) in C. asiatica leaves, elucidating the influence of chromatin organization on expression WGD-derived genes. Additionally, gene family and functional characterization analysis highlight the key role of CasiOSC03 in α-amyrin production while also revealing significant expansion and high expression of CYP716, CYP714, and UGT73 families involved in asiaticoside biosynthesis compared to other Apiaceae species. Notably, a unique and large UGT73 gene cluster, located within the same TAD, is potentially pivotal for enhancing triterpenoid saponin. Weighted gene co-expression network analysis (WGCNA) further highlighted the pathways modulated in response to MeJA, offering insights into the regulatory networks governing saponin biosynthesis. This work not only provides a valuable genomic resource for C. asiatica but also sheds light on the molecular mechanisms driving the biosynthesis of pharmacologically important metabolites.