title: Gene duplication and divergence affecting drug content in Cannabis sativa.
abstract: Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency.
authors.affiliation: Department of Plant Biology and Bell Museum, University of Minnesota, 250 Biological Science Center, 1445 Gortner Ave., St Paul, MN, 55108, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Weiblen
authors.affiliation: Department of Plant Biology and Bell Museum, University of Minnesota, 250 Biological Science Center, 1445 Gortner Ave., St Paul, MN, 55108, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Wenger
authors.affiliation: Department of Plant Biology and Bell Museum, University of Minnesota, 250 Biological Science Center, 1445 Gortner Ave., St Paul, MN, 55108, USA.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Craft
authors.affiliation: National Center for Natural Product Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: ElSohly
authors.affiliation: National Center for Natural Product Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Mehmedic
authors.affiliation: Department of Plant Biology and Bell Museum, University of Minnesota, 250 Biological Science Center, 1445 Gortner Ave., St Paul, MN, 55108, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Treiber
authors.affiliation: Department of Plant Biology and Bell Museum, University of Minnesota, 250 Biological Science Center, 1445 Gortner Ave., St Paul, MN, 55108, USA.
authors.forename: M David
authors.initials: MD
authors.lastname: Marks
mesh_terms: D000483:Alleles; D002186:Cannabinoids / Q000235:genetics* / Q000378:metabolism; D002188:Cannabis / Q000235:genetics* / Q000378:metabolism; D003433:Crosses, Genetic; D013759:Dronabinol / Q000378:metabolism; D020440:Gene Duplication; D017343:Genes, Plant; D008040:Genetic Linkage; D005819:Genetic Markers; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D040641:Quantitative Trait Loci; D012639:Seeds; D013045:Species Specificity
chemical_list: D002186:Cannabinoids; D005819:Genetic Markers; D013759:Dronabinol; D019746:Intramolecular Oxidoreductases; C100678:cannabidiolic acid synthase; C006884:cannabidiolic acid
keywords: cannabidiol (CBD); cannabinoids; domestication; hemp; marijuana; tetrahydrocannabinol (THC)