Research record28 May 2025Journal article
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
Abstract
Cannabis sativa is a globally important seed oil, fibre and drug-producing plant species. However, a century of prohibition has severely restricted development of breeding and germplasm resources, leaving potential hemp-based nutritional and fibre applications unrealized. Here we present a cannabis pangenome, constructed with 181 new and 12 previously released genomes from a total of 144 biological samples including both male (XY) and female (XX) plants. We identified widespread regions of the cannabis pangenome that are surprisingly diverse for a single species, with high levels of genetic and structural variation, and propose a novel population structure and hybridization history. Across the ancient heteromorphic X and Y sex chromosomes, we observed a variable boundary at the sex-determining and pseudoautosomal regions as well as genes that exhibit male-biased expression, including genes encoding several key flowering regulators. Conversely, the cannabinoid synthase genes, which are responsible for producing cannabidiol acid and delta-9-tetrahydrocannabinolic acid, contained very low levels of diversity, despite being embedded within a variable region with multiple pseudogenized paralogues, structural variation and distinct transposable element arrangements. Additionally, we identified variants of acyl-lipid thioesterase genes that were associated with fatty acid chain length variation and the production of the rare cannabinoids, tetrahydrocannabivarin and cannabidivarin. We conclude that the C. sativa gene pool remains only partially characterized, the existence of wild relatives in Asia is likely and its potential as a crop species remains largely unrealized.
The paper's abstract, reproduced as published.
Record created 4 May 2026 · maintained by landrace.wiki editors ·
page history
Published28 May 2025
TypeJournal article
VenueNature
Year2025
2025-05-28
2026-05-04
Domesticated cannabinoid synthases amid a wild mosaic cannabis pangenome
Journal article
Genetics
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.
Cannabis sativa is a globally important seed oil, fibre and drug-producing plant species. However, a century of prohibition has severely restricted development of breeding and germplasm resources, leaving potential hemp-based nutritional and fibre applications unrealized. Here we present a cannabis pangenome, constructed with 181 new and 12 previously released genomes from a total of 144 biological samples including both male (XY) and female (XX) plants. We identified widespread regions of the cannabis pangenome that are surprisingly diverse for a single species, with high levels of genetic and structural variation, and propose a novel population structure and hybridization history. Across the ancient heteromorphic X and Y sex chromosomes, we observed a variable boundary at the sex-determining and pseudoautosomal regions as well as genes that exhibit male-biased expression, including genes encoding several key flowering regulators. Conversely, the cannabinoid synthase genes, which are responsible for producing cannabidiol acid and delta-9-tetrahydrocannabinolic acid, contained very low levels of diversity, despite being embedded within a variable region with multiple pseudogenized paralogues, structural variation and distinct transposable element arrangements. Additionally, we identified variants of acyl-lipid thioesterase genes that were associated with fatty acid chain length variation and the production of the rare cannabinoids, tetrahydrocannabivarin and cannabidivarin. We conclude that the C. sativa gene pool remains only partially characterized, the existence of wild relatives in Asia is likely and its potential as a crop species remains largely unrealized.
