The Isodon serra genome sheds light on tanshinone biosynthesis and reveals the recursive karyotype evolutionary histories within Lamiales.

Abstract

Lamiales is one of the largest orders of angiosperms with a complex evolutionary history and plays a significant role in human life. However, the polyploidization and chromosome evolution histories within this group remain in mystery. Among Lamiales, Isodon serra (Maxim.) Kudô shines for its abundance of diterpenes, notably tanshinones, long used in East Asia to combat toxicity and inflammation. Yet, the genes driving its biosynthesis and the factors governing its regulation linger in obscurity. Here, we present the telomere-to-telomere genome assembly of I. serra and, through gene-to-metabolite network analyses, pinpoint the pivotal tanshinone biosynthesis genes and their co-expressed transcription factors. Particularly, through luciferase (LUC) assays, we speculate that IsMYB-13 and IsbHLH-8 may upregulate IsCYP76AH101, which is the key step in the biosynthesis of the tanshinone precursor. Among Lamiales, Oleaceae, Gesneriaceae and Plantaginaceae successively sister to a clade of seven Lamiales families, all sharing a recent whole-genome duplication (designated as α event). By reconstructing the ancestral Lamiales karyotypes (ALK) and post-α event (ALKα), we trace chromosomal evolution trajectories across Lamiales species. Notably, one chromosomal fusion is detected from ALK to ALKα, and three shared chromosomal fusion events are detected sequentially from ALKα to I. serra, which fully supports the phylogeny constructed using single-copy genes. This comprehensive study illuminates the genome evolution and chromosomal dynamics of Lamiales, further enhancing our understanding of the biosynthetic mechanisms underlying the medicinal properties of I. serra.