Researchers finally discover the genes that produce THC and CBD

Animal and plant DNA shares the shape of the double helix.
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While the genome of the cannabis plant was sequenced in 2011, the researchers struggled to isolate the genes responsible for producing the two most important chemicals in the plant.

Until now. A joint Canada-US effort has helpedidentifier the genes that produce THC (the component that causes hovering) and CBD (the compound best known for its medical applications).

Humans have been consuming cannabis for millennia, but scientists are still largely unaware of the birth of the plant's chemical compounds (cannabinoids) that affect humans ... However a discovery revealed by the first cannabis genome map, detailing thus the arrangement of the genes on the chromosomes, reveals to us that old ancient viruses would have colonized the genome of the plant and accelerated the evolutionary process of its DNA to offer us the THC and CBD...

The main obstacle to discovering these genes was the abundance of what researchers call "junk DNA", genetic information that was dumped into the genome of cannabis by viruses during the years of its evolution. In fact, between 70 and 75 percent of marijuana and hemp DNA comes from these retroviral sources, says Tim Hughes, a molecular geneticist at the Donnelly Center for Cellular and Biomolecular Research at the University of Toronto.

For example retroviruses: like HIV, are able to insert their DNA into the genomes of other species, says Hughes.

"Humans, plants, and virtually all organisms have something like that - about half of the human genome goes back to viral sources.

According to researchersThis discovery will greatly facilitate the manipulation of medicinal THC and CBD levels contained in the plant to meet the varied preferences of patients in the newly legalized Canadian market.

"You can only handle a gene when you know where it is"

said Harm van Bakel, one of the collaborators of the study, who is also an expert in genomics at the Icahn School of Medicine in Mount Sinai, New York.

"And you also need to know about the rest of the genome sequencing so you can uniquely target the gene of interest and not be distracted by ... other things that look like it," Bakel said. The Toronto Star.

But not only did this mass of viral DNA prevent researchers from seeing the THC and CBD genes, but it probably also contributed to their development. Hughes says that the cellular mechanisms that would normally maintain the genetic order can be countered by the long and repeated sequences of the surrounding viral DNA. And instead of keeping the genes in their original form, the faulty mechanisms would have reorganized their sequencing to produce the current genetic patterns. Exposing cellular mechanisms to viral DNA can cause errors that lead to genetic changes in plants such as cannabis.

According to Tim Hughes, these "mistakes" have "almost certainly" favored the development of the THC and CBD genes of the plant.

The study, of which a preliminary version was published online this month by the journal Genome Research, has also shown that THC and CBD are produced by distinct genes.
The existence of another active gene that produces a product known as cannabichromone, or CBCmay have both medicinal and slightly intoxicating effects in humans.

Another reason the genes had escaped scientists was the illegal status of the plant. Ironically, although we understand quite well how THC and CBD affect humans, we do not know how the genes that produce them are for the plant itself.

The discovery of the genes will make it much easier to grow cannabis with specific levels of the two primary compounds. It also allows researchers to determine which genes are responsible taste and smell which characterize the different strains. Yet, even though the genome with 10 chromosomes was sequenced in 2011, the location of these key genes has remained hidden in an ocean of viral DNA until today ...

The chromosomal map of cannabis

"The chromosomal map is an important fundamental resource for the pursuit of research that, despite the widespread use of cannabis, has lagged behind other cultures due to restrictive legislation," says Tim Hughes, professor at Donnelly Center for Cellular and Biomolecular Research and co-founder of the study.

According to Hughes, these viruses could have accelerated a process of evolution that resulted in the mutation of a single enzymatic gene in cannabis into two genes, which would eventually have given us THC and CBD.

"Proteins [for THC and CBD] are embedded in this huge mess of virus-like sequences. These sequences are known to facilitate rearrangement of the chromosome, and they are actually a bit dangerous. "

Old viruses have contributed to the evolution of hemp

The THC and CBD producing enzymes are encoded by the THCA and CBDA synthetic cannabidiolic acid genes, respectively. Both are on the 6 chromosome of the ten chromosomes in which the cannabis genome is conditioned. There, the genes of the enzyme are surrounded by large swaths of scrambled DNA from viruses that colonized the genome millions of years ago. This viral DNA, or retro-elements as it is called, has made copies of itself that have spread through the genome by leaping into other sites of the host cell's DNA.

The genetic sequences of the THCA and CBDA synthases are almost identical, which confirms the idea that they come from the same gene that was duplicated millions of years ago. Over time, one or both copies of the gene became scrambled by invading retroelements and, evolving separately, they eventually produced two different enzymes: CBDA synthase found in hemp (fiber type) and THCA synthase in the drug type (marijuana).

It's hard to tell what cannabis looked like before the ancient viruses helped it develop the properties we know today. But according to Hughes, some of his closest relatives are harmless plants like mulberry and hops ...

Researchers expect the map to accelerate breeding efforts to create new strains with the desired medical properties as well as varieties that can be grown more sustainably or with increased resistance to diseases and pests.

As the enzymes are so similar at the DNA level, it was not even clear until this study whether they are encoded by distinct genes or by two versions of the same gene. The fact that most strains produce both CBD and THC despite the efforts of breeders to grow HTV-free hemp varieties for users seeking to avoid it has added to the confusion.

The chromosomal map now clearly shows that two distinct genes are at play, which should allow them to be separated during breeding to grow THC-free plants.

What's the point?

Such cards are essential to improve our impoverished understanding of the cannabis plant. The map of Hughes and colleagues is already paying dividends beyond the discovery of the possible role of viruses in the production of THC and CBD. According to the researchers, they also identified a gene responsible for producing a third cannabinoid called CBC.

And there is still much to learn about a plant that many people consume regularly, but science has not yet understood.

According to Hughes, "It is by chance that THC and CBD have effects on people, assuming that these compounds have developed well before humans walk on Earth ...

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