First telomere-to-telomere (T2T) licorice genome uncovers key genes for medicinal metabolite biosynthesis and desert stress adaptation

Licorice (Glycyrrhiza genus) is one of the most important traditional-medicine herbs worldwide, widely used in pharmaceuticals, food and industrial manufacturing. Three species, Glycyrrhiza uralensis, G. inflata and G. glabra, are officially recorded in the Chinese Pharmacopoeia. Their roots and rhizomes produce valuable bioactive compounds including glycyrrhizic acid, liquiritin, licochalcone A and glabridin. However, the lack of near-complete genome assemblies has long limited our understanding of metabolite biosynthesis and environmental adaptation mechanisms in licorice.

A research team led by Professor Hongbin Li from Shihezi University generated the first gap-free telomere-to-telomere (T2T) genome of G. uralensis, resolving all eight chromosomes with complete telomeres and centromeres. Centromeric repeat monomers Cen60 and species-specific Cen307 on chromosome 4 were confirmed by FISH cytological experiments. In parallel, chromosome-level genome assemblies were produced for G. uralensis, G. inflata and G. glabra.

Using re-sequencing data from 188 wild Xinjiang licorice accessions, the team built a large-scale genomic-variation map. Population-genomic analyses uncovered clear geographic-genetic differentiation shaped by the Tianshan Mountains: G. uralensis mainly inhabits the Xinjiang northern region (XJN), while G. inflata dominates the Xinjiang southern region (XJS), and G. glabra occurs across the whole region. The team delineated core germplasm groups for G. uralensis and G. inflata and detected extensive inter-species introgression.

Selective-sweep scans identified dozens of key genes under selection related to triterpenoid and flavonoid biosynthesis. Integrating tissue transcriptomes, abiotic stress RNA-seq, climate-correlation analysis and genome wide association study (GWAS), researchers pinpointed gene 4CL5 as a major determinant of licochalcone A accumulation. Further molecular experiments including yeast one-hybrid, dual-luciferase and EMSA verified that transcription factor GiPHL1 binds the P1BS cis-element of the Gi4CL5 promoter. The GiPHL1-Gi4CL5 module simultaneously promotes licochalcone A biosynthesis and improves stress resistance in G. inflata, which helps this species survive the hot, arid habitats of XJS.

This study provides unprecedented high quality genomic resources for licorice. The uncovered candidate genes and molecular markers will accelerate precision breeding toward licorice varieties with higher medicinal compound yield and enhanced stress tolerance, and support synthetic biology research for producing licorice derived active substances.

Funding for this work was provided by grants from the National Natural Science Foundation of China, Science and Technology Project of Bingtuan, and the Tianchi Talent Project of Xinjiang.

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