Uncovering the Biochemical and Genetic Secrets of Cannabis

Cannabis sativa L. (marijuana, hemp; Cannabaceae) is an ancient crop plant that produces nutritious seeds, high-quality fibre and bioactive cannabinoids e.g. delta⁹-tetrahydrocannabinol (THC). We are using genomics to elucidate the cannabinoid metabolic pathway and to better understand the genetic organization of the genus Cannabis. A major experimental approach has been the use of gene expression data from glandular trichomes, the specialized epidermal structures that synthesize cannabinoids. We have successfully applied trichome-focused analysis in combination with classical biochemistry to identify three enzymes of the cannabinoid pathway: hexanoyl-CoA synthetase, olivetolic acid cyclase and an aromatic prenyltransferase. A draft assembly of the ~820 Mbp genome from the marijuana strain Purple Kush, has opened up new avenues for gene discovery as shown by the identification of a novel cannabinoid synthase enzyme, cannabichromenic acid synthase. We have recently used genotyping-by-sequencing (GBS) to analyze the genetic variation in 43 hemp and 81 marijuana accessions. GBS shows that hemp and marijuana are genetically distinct, and provides insight into the differentiation of marijuana into “Indica” and “Sativa” groups. As cannabis emerges from the shadow of prohibition, genomics promises both to clarify its evolutionary history and to accelerate the development of this valuable, multi-use crop.