Bigger is better: modern Cannabis trichomes are larger and more productive than their landrace ancestors

Abstract Cannabis sativa L. (Cannabis) is a medicinal plant that produces and stores an abundance of therapeutic and psychoactive secondary metabolites, including phytocannabinoids and terpenes, in the glandular trichomes of its female flowers. We postulate that glandular trichome productivity has been under strong artificial selection in the pursuit for ever more potent cultivars. By comparing glandular trichomes of two modern cultivars and two traditional landraces, contrasting for cannabidiol and tetrahydrocannabinol contents, this study aims to identify drivers of enhanced phytocannabinoid productivity in improved drug cultivars. Fluorescent light microscopy, targeted metabolite analysis, and quantitative proteomics were used to examine differences in trichome morphology and metabolic activity. The increased concentrations of phytocannabinoids and terpenes of modern cannabis cultivars were reflected in larger trichomes that contained more secretory cells compared to traditional landraces. Proteomic analysis indicated that these modern trichome phenotypes were supported by increased metabolic activity, particularly in pathways related to energy production and lipid metabolism. Weighted Gene Co-expression Network Analysis suggested that histone H2A involved in DNA repair, regulator of fatty acid composition 3 involved in non-photosynthetic plastid development and olivetolic acid cyclase involved in phytocannabinoid biosynthesis are central hub proteins associated with high tetrahydrocannabinolic acid production. This study highlights the morphological and molecular differences observed between the specific modern and traditional Cannabis cultivars analysed in this study, offering valuable insights for enhancing phytocannabinoid production through targeted breeding and biotechnological approaches.