Manipulating Cannabis Genetics

"You can only manipulate a gene when you know where it is located. And you also need to know something about the rest of the sequencing in the genome so that you can uniquely target the gene of interest and not be side-tracked by --- other things that look similar."
Harm van Bakel, genomic expert, Icahn School of Medicine, Mount Sinai Hospital, New York

"Humans, plants, virtually all organisms have something like this [embedded retroviruse DNA].
"[The machinery] that's normally responsible for keeping things tidy and organized gets confused when it sees multiple copies of the same thing, and it makes mistakes."
"That is almost certainly what has happened [with the THC and CBD genes in cannabis]."
"Until the last couple of years, it's been extremely difficult to work with it [cannabis] legally. The repercussions of being caught with a huge number of marijuana strains in order to do genetic experiments -- nobody would risk that."
Tim Hughes, molecular geneticist, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto

Cannabis sativa plant (photo by michael fischer)

Now, however, since the October 17 recreational cannabis legalization legislation has taken effect in Canada, research can commence on a grand scale. Dr. van Bakel foresees Canada becoming the go-to place for marijuana research into the plant and its hallucinogenic as well as medicinal effects. The latest-generation scanners for example are capable of capturing tens of thousands of the base pairs that produce the twisting DNA molecul which older technology could sequence only excruciatingly slowly, making advances in research far more possible.

As was done when the research team comprised of Canadian and U.S. scientists were enabled to locate the genes responsible for the kick that cannabis produces when they located the THC and CBD genes on the plant's sixth chromosome, owing to the aid given them by improved genetic scanning technology. One of the intriguing points of interest for research is to understand what the genes producing THC and CBD effect for the plant itself, even while it is well enough understood how THC and CBD affect humans.

The study in question was released this month b the online journal Genome Research, which concluded:

• Definitively that THC and CBC are produced by separate genes;
• The existence of another active gene that produces a product known as cannabichromone (CBC) which can have both medicinal and slightly intoxicating effects in humans;
• The location of a gene that helps to determine the potency of different cannabis strains.

Although it was well enough known for decades what the chemical makeup of the genes producing THC and CBD were  -- the two main cannabinoids found in marijuana -- what was not known was where they could be found. Cannabis's 10-chromosome genome had been sequenced in 2011, but the location of these genes remained a mystery; unknown was where they were in a maze of viral DNA. It may seem strange to speak of viral DNA but all species, including humans can be infested with DNA from viruses.

Marijuana and hemp plants, sharing a common ancestor, see 70 to 75 percent of their DNA derived from retrovirus sources, explains Dr. Hughes. The research's success in discovering just where the genes responsible for the cannabinoids were to be found, hidden among "junk" DNA left in the plant's genome by viruses during its evolutionary phase will make it infinitely more efficient to manipulate levels of intoxicating THC and medicinal CBD.

That will be done with a view to producing a product amenable to variations reflecting preferences in the legalized Canadian market. The scientists have concluded that the viral DNA in cannabis played a key role in creating random genetic rearrangements to produce the active forms of THC and CBD in an inert plant. Had the viral DNA not been present, that transformation and presence of those genes would in all likelihood never have occurred. Cellular mechanisms that normally maintain genetic order can be circumvented by lengthy and repeated sequences of the surrounding viral DNA.

The faulty mechanisms that result would rearrange their sequencing to produce the genetic configurations seen today rather than presenting the genes in their original form. Now research can continue apace in the new political climate of legalization along with the use of more technically advanced instruments, scanners capable of capturing tens of thousands of base pairs as opposed to the technology they have replaced which could sequence a mere several hundred at a time.

Although the plant’s genome had been sequenced in 2011, the location of some genes remained hidden in a sea of viral DNA.  (Steven Senne / The Associated Press)