Domesticated cannabinoid synthases amid a wild mosaic cannabis pangenome
Ryan C. Lynch, Lillian K. Padgitt-Cobb, Andrea R. Garfinkel, Brian J. Knaus, Nolan T. Hartwick, Nicholas Allsing, Anthony Aylward, Philip C. Bentz, Sarah B. Carey, Allen Mamerto, Justine K. Kitony, Kelly Colt, Emily R. Murray, Tiffany Duong, Heidi I. Chen, Aaron Trippe, Alex Harkess, Seth Crawford, Kelly Vining, Todd P. Michael
Nature· 2025
Cannabis pangenome built from 193 genomes (181 new PacBio assemblies plus 12 previously published) representing 144 biological samples and including both male (XY) and female (XX) plants. Comprises 78 haplotype-resolved chromosome-scale assemblies and 103 contig-level assemblies. Reports widespread regions of high genetic and structural variation and proposes a population structure and hybridisation history for the species. Resolves the heteromorphic X and Y sex chromosomes, including a variable boundary at the sex-determining and pseudoautosomal regions and male-biased expression of several flowering regulators. Finds low diversity at the cannabinoid synthase loci (CBDAS, THCAS) despite their location within a region containing pseudogenised paralogues, structural variation and distinct transposable element arrangements. Identifies acyl-lipid thioesterase variants associated with fatty acid chain length and with the production of the propyl cannabinoids THCV and CBDV. Confirms that high-CBD hemp lineages such as CBDRx emerged through introgression of the CBDAS locus into a predominantly drug-type genetic background. The authors conclude that the Cannabis sativa gene pool remains only partly characterised and that wild relatives likely persist in Asia.
2025-05-28
2026-05-04
Domesticated cannabinoid synthases amid a wild mosaic cannabis pangenome
Journal article
Ryan C. Lynch, Lillian K. Padgitt-Cobb, Andrea R. Garfinkel, Brian J. Knaus, Nolan T. Hartwick, Nicholas Allsing, Anthony Aylward, Philip C. Bentz, Sarah B. Carey, Allen Mamerto, Justine K. Kitony, Kelly Colt, Emily R. Murray, Tiffany Duong, Heidi I. Chen, Aaron Trippe, Alex Harkess, Seth Crawford, Kelly Vining, Todd P. Michael
Nature
2025
10.1038/s41586-025-09065-0
https://www.nature.com/articles/s41586-025-09065-0
https://www.nature.com/articles/s41586-025-09065-0.pdf
The first comprehensive cannabis pangenome, built from 193 genomes (181 new PacBio assemblies plus 12 previously published) representing 144 biological samples spanning use types, history, sex expression and agronomic traits. Includes 78 haplotype-resolved chromosome-scale assemblies and 103 contig-level assemblies covering both male (XY) and female (XX) plants. Documents surprisingly high genetic and structural variation for a single species and proposes a new population structure and hybridisation history. Resolves the heteromorphic X and Y sex chromosomes for the first time, including a variable boundary at the sex-determining and pseudoautosomal regions and male-biased expression of several flowering regulators. Finds that the cannabinoid synthase loci (CBDAS, THCAS) themselves carry very little diversity despite sitting in a region rich in pseudogenised paralogues, structural variation and distinct transposable element arrangements, evidence that the synthases have been recently domesticated against an otherwise wild-mosaic genomic background. Identifies acyl-lipid thioesterase variants associated with fatty acid chain length and with the production of the rarer propyl cannabinoids THCV and CBDV. Confirms that high-CBD hemp lineages such as CBDRx emerged through introgression of the CBDAS locus into a predominantly drug-type genetic background. Concludes that the Cannabis sativa gene pool remains only partly characterised, that wild relatives likely persist in Asia, and that the crop's broader potential is largely unrealised. Provides the new reference framework for placing landrace genotypes in a global population context and underwrites the conservation case that elite modern cultivars have lost diversity that landraces and wild-growing populations still hold.
