The first complete map of the Cannabis sativa plant’s genome has revealed that ancient viruses caused the genes encoding tetrahydrocannabinol (THC) and cannabidiol (CBD) to evolve from a single ancestral gene.
Now presented in the journal Genome Research, the new resource also reveals the sequence and location of the gene responsible for cannabichromene (CBC) – a non-psychoactive cannabinoid that hasn’t received the same fanfare or scientific analysis as THC and CBD, but that recent investigations have suggested may have potent anti-inflammatory properties.
The authors, a collaborative group of scientists from the Icahn School of Medicine at Mt Sinai, the Aurora Cannabis company, and the University of British Columbia, predict that their findings will aid medicinal growers and researchers in the ongoing effort to breed strains with more exact cannabinoid profiles. Additionally, the work could lead to marijuana plant lineages that are more productive, pest-resistant, and – by requiring less light and water – more sustainable.
"The chromosome map is an important foundational resource for further research which, despite cannabis' widespread use, has lagged behind other crops due to restrictive legislation," co-lead author Tim Hughes, a professor of cellular and biomolecular research and molecular genetics at the University of Toronto, said in a statement.
Prior to the team’s complete map, scientists had a poor grasp on how hemp and drug-type strains of the Cannabis sativa species produced such a variety of cannabinoid profiles. Hemp plants, which have been grown for their sturdy fiber for thousands of years, grow flowers rich in the non-psychoactive yet incredibly medicinal CBD, whereas the stains we humans have bred to create recreational drugs are high in mind-warping THC. Based on the fragmented and incomplete genome maps researchers had assembled previously, it was clear that the genes for THC and CBD were incredibly similar sequence-wise, yet it remained unknown whether the compounds were the result of a single gene, two copies of the same gene, or two separate genes.
Hoping to resolve such mysteries once and for all, Hughes and his colleagues used advanced sequencing technology to read the entire, 10-chromosome genome of a hybrid plant cross-bred from a "Purple Kush" drug strain and a hemp variety called "Finola".
The resulting map of hundreds of millions of base pairs shows that the enzymes that make THC and CBD are encoded by the THCA and CBDA synthase genes, respectively. Both genes are located on chromosome 6, within a large region of junky, non-coding DNA that bears the hallmark features of retroelements – sections of viral DNA that infiltrated the genome over the course of evolution, as generations of the plants’ ancestors were infected by viruses. Once introduced into a host’s DNA, the retroelements replicate themselves and spread throughout the genome, sometimes inserting themselves harmlessly into non-coding regions and other times inducing mutations by interrupting the sequence of a gene.
"Plant genomes can contain millions of retroelement copies," stated co-author Harm van Bakel.
After examining the entire THCA and CBDA region, the team concluded that the genes likely arose when a single precursor gene was duplicated and the two versions diverged slightly after the introduction of retroelements. Then, after selective breeding by humans, the non-coding chromosome 6 sequences diverged even further, though the THCA and CBDA sequences remained very similar.
Armed with this new knowledge, the authors note that growers will finally be able to grow high-CBD strains with no THC.
As of now, no lineages of medicinal marijuana are entirely free of THC, so creating zero-THC, CBD products – a revolution for people with seizure disorders, anxiety, and chronic pain, among other conditions – involve chemical extraction processes.