How an Ancient Virus Created Cannabis

Researchers at the U of T have found that an ancient virus created and colonized the effects of what we know as THC and CBD today. These bioactive substances are used medicinally and recreationally around the world. The world’s first cannabis chromosome map revealed the plant’s evolutionary past and points to its future as a potential medicine.

These recent discoveries show the details of the long-awaited cannabis genome map. Showing gene arrangement on the chromosomes, published by the Genome Research journal. During this revolutionary discovery, scientists have found that the gene responsible for the production of cannabichromene or CBC the lesser known cannabinoid, as the active ingredient in cannabis are known and new understandings of how strain potency is determined

“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,” says Tim Hughes, a professor in the Donnelly Centre for Cellular and Biomolecular Research and co-leader of the study. Hughes is also a professor in the Department of Molecular Genetics and Senior Fellow at the Canadian Institute for Advancement of Research.

The scientists expect that this mapping of the genes will speed the breeding processes in creating new strains with desired THC/CBD properties as well as varieties that can be grown with less economic harm, or increases to resistance such as pests, diseases and mould.

The study was a three-part effort between Tim Hughes’ team and those of Jonathan Page, of Aurora Cannabis and the University of British Columbia, and Harm van Bakel, of the Icahn School of Medicine at Mt Sinai in New York.

Hughes, Page and van Bakel collaborated in 2011 when they released the first draft of cannabis genome which was too shattered to reveal gene position on chromosomes.

The new project shows how the map reveals how hemp and marijuana, which belong to the same species Cannabis sativa, evolved as a separate strain. The chemical properties are shown to be distinct with distinct. Cannabis plants harvested for drug use due to its abundance in psychoactive tetrahydrocannabinol, or THC, whereas hemp produces cannabidiol, or CBD, lately in high demand for its medicinal properties. Some people use CBD to relieve pain, and it is also being tested as a treatment for epilepsy, schizophrenia and Alzheimer’s.

The enzymes making THC and CBD are encoded by THCA and CBDA synthase genes, respectively. Both are found on chromosome 6 of the ten chromosomes the cannabis genome is packaged into. There, the enzyme genes are surrounded by vast swathes of garbled DNA which came from viruses that colonized the genome millions of years ago. This viral DNA, or retroelements as it is known, made copies of itself that spread across the genome by jumping into other sites in the host cell’s DNA.

“Plant genomes can contain millions of retroelement copies,” says van Bakel, an assistant professor in the Icahn Institute for Data Science and Genomic Technology in New York and the Department of Genetics and Genome Sciences. “This means that linking genes on chromosomes is analogous to assembling a huge puzzle where three-quarters of the pieces are nearly the same colour. The combination of a genetic map and PacBio sequencing technology allowed us to increase the size of the puzzle pieces and find enough distinguishing features to facilitate the assembly process and pinpoint the synthase genes.”

The scientists believe that gene replication of the ancestral synthase gene and expanding retroelements began to divide ancient cannabis into chemically distinct types. Humans then selected for plants containing desirable chemistry such as genetics high THC.

The gene sequences for the THCA and CBDA synthases are nearly identical giving support to the idea that they come from the same gene which was replicated millions of years ago. Over many years, one or both gene copies became mixed by invading retroelements, and by evolving separately, they eventually came to produce two different enzymes — CBDA synthase found in hemp (fibre-type), and THCA synthase in drug-type (marijuana).

Because the enzymes are so same on so many DNA levels until this study it was not even clear if they are encoded by separate genes or by two versions of the same gene. Adding to the confusion was the fact that most strains produce both CBD and THC despite growers or farmers efforts to grow certain hemp varieties free from the mind-altering THC for users looking to avoid it.

The chromosome map now clearly shows that two distinct genes are present which should make it possible to separate them during breeding to grow plants without THC.

Some psychoactive effects in medical strains could be coming from a lesser-known cannabinoid that has unusual pharmacology including anti-inflammatory properties. The discovery of the gene responsible for CBC synthesis will make it so that it is possible for growers to tailor its content in future genetics
“Mainstream science has still not done enough because of research restrictions,” says Page, of UBC and Chief Scientific Officer at Aurora, one of Canada’s largest producers of medical cannabis. “Legalization and looming ease of research regulation provide for opportunities for more research to be done. And Canada is leading the way.”

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