SNP in Potentially Defunct Tetrahydrocannabinolic Acid Synthase Is a Marker for Cannabigerolic Acid Dominance in Cannabis sativa L.

Rojas

et al. 2021

Genes

Self Cite

Hemp (Cannabis sativa L.) has recently become an important crop due to the growing market demands for products containing cannabinoids. Unintended cross-pollination of C. sativa crops is one of the most important threats to cannabinoid production and has been shown to reduce cannabinoid yield. Ploidy manipulation has been used in other crops to improve agronomic traits and reduce fertility; however, little is known about the performance of C. sativa polyploids. In this study, colchicine was applied to two proprietary, inbred diploid C. sativa inbred lines, ‘TS1-3’ and ‘P163’, to produce the tetraploids ‘TS1-3 (4x)’ and ‘P163 (4x)’. The diploid, triploid, and tetraploid F1 hybrids from ‘TS1-3’ × ‘P163’, ‘TS1-3 (4x)’ × ‘P163’, and ‘TS1-3 (4x)’ × ‘P163 (4x)’ were produced to test their fertilities, crossing compatibilities, and yields. The results indicated a reduction in fertility in the triploids and the tetraploids, relative to their diploid counterparts. When triploids were used as females, seed yields were less than 2% compared to when diploids were used as females; thus, triploids were determined to be female infertile. The triploids resulting from the crosses made herein displayed increases in biomass and inflorescence weight compared to the diploids created from the same parents in a field setting. Statistical increases in cannabinoid concentrations were not observed. Lastly, asymmetric crossing compatibility was observed between the diploids and the tetraploids of the genotypes tested. The results demonstrate the potential benefits of triploid C. sativa cultivars in commercial agriculture.

Section: Methodsmentioning

confidence: 99%

“…Analyses of cannabinoid content of the inflorescences were performed according to a modified protocol described by Vaclavik et al [ 27 ]; details regarding the modifications can be found in Garfinkel et al [ 25 ]. Five to 10 randomly chosen dried inflorescences from each plant were collected and used in the analysis.…”

Section: Methodsmentioning

confidence: 99%

Characteristics of the Diploid, Triploid, and Tetraploid Versions of a Cannabigerol-Dominant F1 Hybrid Industrial Hemp Cultivar, Cannabis sativa ‘Stem Cell CBG’

Rojas

et al. 2021

Genes

Self Cite

“…Thus, harvesting hemp very early yields higher levels of CBGA compared to later in the plant’s life. In addition, some cultivars have increased yields of CBGA through selective breeding to inhibit its transformation into other cannabinoids during the plant’s maturation ( Garfinkel, et al, 2021 ). Similar to CBDA, CBGA displays low affinity for both the CB1 and CB2 receptors ( Navarro, et al, 2020 ).…”

Section: Minor Cannabinoid Pharmacology and Therapeuticsmentioning

confidence: 99%

Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

2021

The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders. This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.

Genome Biology and Evolution

“…This is probably due to a single amino acid mutation leading to a defective (B T0 ) variant ( Onofri et al 2015 ). Recently, a different CBGA-dominant cultivar was found to have another single amino acid mutation in THCAS ( Garfinkel et al 2021 ). Gene copy number variation has been suggested based on amplicon sequencing of the THCAS locus ( McKernan et al 2015 ; Weiblen et al 2015 ; Vergara et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Origin and Evolution of the Cannabinoid Oxidocyclase Gene Family

Velzen¹,

Schranz²

2021

Cannabis is an ancient crop representing a rapidly increasing legal market, especially for medicinal purposes. Medicinal and psychoactive effects of Cannabis rely on specific terpenophenolic ligands named cannabinoids. Recent whole-genome sequencing efforts have uncovered variation in multiple genes encoding the final steps in cannabinoid biosynthesis. However, the origin, evolution, and phylogenetic relationships of these cannabinoid oxidocyclase genes remain unclear. To elucidate these aspects, we performed comparative genomic analyses of Cannabis, related genera within the Cannabaceae family, and selected outgroup species. Results show that cannabinoid oxidocyclase genes originated in the Cannabis lineage from within a larger gene expansion in the Cannabaceae family. Localization and divergence of oxidocyclase genes in the Cannabis genome revealed two main syntenic blocks, each comprising tandemly repeated cannabinoid oxidocyclase genes. By comparing these blocks with those in genomes from closely related species we propose an evolutionary model for the origin, neofunctionalization, duplication, and diversification of cannabinoid oxidocycloase genes. Based on phylogenetic analyses, we propose a comprehensive classification of three main clades and seven subclades that is intended to aid unequivocal referencing and identification of cannabinoid oxidocyclase genes. Our data suggest that cannabinoid phenotype is primarily determined by presence/absence of single-copy genes. Although wild populations of Cannabis are still unknown, increased sampling of landraces and wild/feral populations across its native geographic range is likely to uncover additional cannabinoid oxidocyclase sequence variants.