The Viruses That Gave Cannabis its High

A new cannabis genome map has revealed that the plant’s CBD and THC genes probably came from viral DNA.

The finding is just one of the many insights gleaned from the newly published cannabis genome map, which details the plant’s chromosome and gene arrangements.

Other findings included revelations into the production of cannabichromene (CBC) and how strain potency can be determined.

The map, which was produced in a collaboration between Canadian and USA universities and research facilities, bears many similarities to another recent ‘genetic map of cannabis’ produced by the Craig Venter Institute and other institutions.

Like that team, the Canadian-USA collaboration hopes their map will go on to inform new varieties of bespoke cannabis.

The peer-reviewed research was published in the journal Genome Research.

When cannabis went viral

The cannabis industry wouldn’t be the rapidly growing field it is today without two unique compounds: THC (tetrahydrocannabinol) and CBD (cannabidiol). According to the latest cannabis genome map, credit for these two chemicals should go to some infectious viruses that colonized the plant’s genome millions of years ago.

Certain viruses, known as retroviruses, replicate by injecting their own genetic material into the DNA of their host cell. The hijacked cell then reproduces the virus’ proteins, which assemble into a new virus and the cycle continues.

The Canadian-USA researchers hypothesize that, long ago, a similar virus injected its genes into the ancestors of cannabis plants. These genes were the precursors for THCA and CBDA synthase genes and soon (evolutionary speaking) the plants started to produce these unique compounds for themselves.

"Plant genomes can contain millions of retroelement copies," says Assistant Professor Harm van Bakel, one of the principal researchers from the Icahn School of Medicine at Mount Sinai in New York.

In a press statement, Bakel described how the researchers sequenced cannabis plants and created the new genome map. He explains that "Linking genes on chromosomes is analogous to assembling a huge puzzle where three-quarters of the pieces are nearly the same color. 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."

Both of these synthase genes are found on chromosome 6 (out of 10) within the cannabis genome, but are surrounded by large chunks of ‘junk DNA’, which probably came from the first invasive viruses.

But retroviruses didn’t stop there. The researchers believe that these retroelements mutated and infected ancient cannabis plants with different variations, leading the species to split into chemically distinct types. Humans then came along and further aided this divergence by selectively breeding for high-THC and high-CBD varieties.

Of course, this millennia-spanning theory is difficult to prove, but the researchers’ new cannabis genome map shows that the gene sequences for the THCA and CBDA synthases are nearly identical. This means its highly likely that they come from the same gene that was duplicated millions of years ago.

Aside from the major cannabinoids, the plant’s famed psychoactive effects could also be due to CBC, which is mainly understood to have anti-inflammatory properties. The researchers claim to have discovered the gene responsible for the cannabinoid’s production and have speculated on its role in psychoactive cultivars (strains).

Mapping cannabis

"The chromosome map is an important foundational resource for further research which, despite cannabis's widespread use, has lagged behind other crops due to restrictive legislation," says Tim Hughes, a co-lead on the study and professor at the Donnelly Centre for Cellular and Biomolecular Research.

But the map isn’t the first of its kind. The members of the same Canadian-USA research collaboration first developed a ‘draft genome and transcriptome of C. Sativa’ back in 2011. At the time, the team’s DNA sequencing technology was not quite up to the task and couldn’t discriminate between certain plant varieties. However, the group did manage to demonstrate that around 70% of cannabis’ genome is composed of repeated DNA sequences, or ‘junk DNA’.

Fast forward seven years and suddenly the concept of a cannabis genome is taking off. Just like the Canadian-USA collaboration, researchers from the Craig Venter Institute, Sunrise Genetics Inc. and the universities of Harvard and Minnesota have also been attempting to map the DNA of cannabis plants. And they succeeded.

In an event that bears a striking similarity to the famous race to sequence the human genome (which was contested between Craig Venter’s Celera company and The Human Genome Project), it appears that the two groups have been in a chase to publish the first peer-reviewed research into a genetic map of cannabis. If this is the case, the Canadian-USA collaboration won.

While the results of the Craig Venter collaboration were reported back in November, the paper has not been through a peer-review and so is considered unsubstantiated. Many of the ‘discoveries’ named in that paper are also replicated in the peer-reviewed Canadian-USA research, such as the evolutionary divergence of CBD and THC genes and the genetic difference between hemp- and marijuana-type cannabis cultivars.

Both groups also foresee their map having a profound effect on future cannabis cultivation. The notion is that if growers can learn the locations and variations of their crops’ genes, they can selectively breed cultivars that express desired compounds. The hope is that such practices will lead to genetically bespoke cannabis products, tailored to consumers’ needs.

However, eager buyers may have to wait for some time. While the Canadian-USA collaboration’s map is one of the most complete yet, it’s still missing any cannabis X/Y chromosomes – additions that could reveal even more tantalizing genetic discoveries. With the aid of new DNA scaffolding technologies, the researchers aim to finish their map as soon as possible. Until then, the race continues.