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How The Cannabis Genome Got Mapped: Q&A With Dr. Jonathan Page
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With interest in marijuana research at an all time high, we spoke to the scientist who mapped the first cannabis genome.

Canadian botanist Jon Page, Ph.D, was one of the lead investigators in the first, and so far only, cannabis genome project.

Published in 2011 in the journal Genome Biology, Dr. Page’s findings unraveled the sequencing of some 30,000 genes that make up the genome of Cannabis sativa, using the popular Purple Kush strain as the source.

The genome has since been available online, and has served as a tool for other cannabis researchers around the world. Dr. Page took the time to answer some of our questions about the project and what lies ahead in the field of cannabis genomics.

Q: What inspired you to pursue the cannabis genome project?

From the time I was an undergrad, I’ve been interested in medicinal plants and plants that have beneficial effects on human health. I focus on the biochemistry of medicinal plants, and study the active chemicals and how these chemicals are produced.

When I was a postdoctoral researcher in Germany in the late 90s, I had already started doing some work on cannabis, mainly trying to figure out how the plant makes THC.

I established my own lab at the National Research Council in Saskatoon when I returned to Canada in 2003 and continued research on cannabinoid biosynthesis and things relevant to the Canadian hemp industry. Hemp is a large acreage crop, but it’s still cannabis and has a lot of similar properties to marijuana.

I was doing small scale genomic studies on cannabis when, around 2009, I was contacted by Dr. Tim Hughes, a professor at the University of Toronto who studies genomics in many different organisms including humans and yeast. Tim basically said, ‘this is a fascinating plant and nobody has even attempted to do a whole genome sequencing project on it, yet it has so many uses and so much history with humanity.’ And medical marijuana was gaining more recognition in both the US and Canada at the time.

So we decided to collaborate on the sequencing of the cannabis genome, which merged my interests in plants, enzymes and cannabis specifically and Tim’s interest in genomics. And also, with cannabis being so important culturally, we wanted to focus on a project that would have some impact for society.

Q: What did the project involve?

Our two teams got together and we were able to obtain DNA of the marijuana strain Purple Kush. The reason we picked Purple Kush was that it was a widespread medical and recreational strain being grown in Canada at the time.

I also had access to various hemp cultivars, so we did the sequencing on Purple Kush, but also some re-sequencing of the hemp genome in order to compare the two types. One of the primary goals of our study was to identify the differences between marijuana and hemp on the genomic level.

Q: What were the major findings?

One major finding was that marijuana type cannabis and hemp type cannabis don’t actually differ by that much. For example, there are no extra copies of the genes for the enzymes of the cannabinoid pathway in the marijuana genome. And yet the plant makes much more THC and other cannabinoids. For example, we think Purple Kush contains around 20% THCA, the acid precursor to THC, and the hemp types contain approximately 5% CBDA.

So the differences don’t seem to be in the number of genes for these enzymes, but the fact that the expression of the cannabinoid pathway is turned up in the marijuana type. We suspect that there are specific regulatory controls, called transcription factors, that increased the expression of the genes for the cannabinoid pathways in marijuana. What this points to is that humans have probably been breeding for more potent marijuana by selecting for transcription factors that turn up the expression of these enzymes.

(Photo: Gagne et al., 2012)
(Photo: Gagne et al., 2012)

The other major finding, which wasn’t new but was reinforced by our genomic analysis, is what really differentiates the cannabinoids found in marijuana versus hemp is a single enzyme at the last step of the cannabinoid pathway. In marijuana it’s the THCA synthase enzyme, and it’s the CBDA synthase enzyme in hemp.

Up to that point, the metabolic pathway is the same. But then there’s a genetically encoded switch, in which the allele that dominates differs in marijuana versus hemp. Sometimes you get both. For example, if you cross a THCA type plant and a CBDA type plant, the offspring will have each allele.

Others had described that at the genetic level, but they hadn’t really done it at the genomic level. So we proved that it was the split in the pathway at the last enzyme step that was responsible for this important chemical difference.

Q: Why map the cannabis genome as a whole?

Cannabis is an amazing plant: it produces fibre, edible seed, oil and of course cannabinoids like THC. Sequencing the cannabis genome is an important step in understanding the plant’s properties, and improving them for agriculture and medicine.

We felt making the genome itself available for researchers worldwide could really benefit research on all forms of this plant, both the hemp and marijuana types.

There are a lot of limitations on doing research on cannabis. It’s not an easy plant to have in your lab, as you need to obtain a special exemption or license to work with it. But we made the data available publicly through the web, so other researchers interested in things like cannabis evolution, sex determination, etc. could study aspects of the plant’s biology, even without having to grow the plant.

We really think it was an important step to make the genomic resources available and we hope it encourages others to do research on the plant.

The paper has been read by many people since being published, in the sense that it has been accessed more than 47,000 times through the journal website (genomebiology.com/2011/12/10/R102). It’s also been cited by a number of other papers. For example, a recent study from the UK, where they were attempting to breed hemp for different oil profiles.

Q: Is there anything particularly unique about the cannabis genome?

Cannabinoid production is unique to cannabis. No other plants that we know of have that capacity. So the genes that encode the enzymes required to produce cannabinoids are absolutely unique to the cannabis genome.

But overall, there wasn’t anything in the genome that we found exceptionally different from other plants closely related to it. For example, apples and strawberries are in a similar group as cannabis, and their genomes are known and cannabis was comparable to those.

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Also, cannabis is closely related to hops. Humulus (hop) and Cannabis are the only two members of the Cannabaceae family. So those two plants are really, really close.

Q: What applications are there for cannabis genomics?

Plant breeding more and more relies on genomic tools. So as plant breeders want to develop new varieties of plants – whether they work on crop plants like wheat or medicinal plants like marijuana – the genome can be used to identify variations in the plants that are desirable. For example, you could breed for specific cannabinoid profiles if you knew the combinations of genes that are involved.

The other application is being able to sort out different strains and different variants in the hemp and marijuana areas. Marijuana in particular has thousands of strains, which have all sorts of interesting names, smells and shapes. What underlies all that variation are differences in the genome.

So applied genomics could be used to understand what makes different strains useful and interesting or also to identify them. For example, understanding the difference between Indica versus Sativa, which scientifically is not very well known at this point.

(Photo: kindgreenbuds.com)
(Photo: kindgreenbuds.com)
Q: What about genetically modified cannabis?

I can say it hasn’t been achieved yet, in the sense that there is no genetically modified cannabis plants. As a scientist, I’m not opposed to genetic modification as a general concept, it just hasn’t been successfully applied in cannabis.

Also, a lot of what we’re finding is modern techniques of breeding can achieve many of the same outcomes of genetic modification. So I’m not 100 percent convinced that we need genetic modification in cannabis. But it’s probably something that will be attempted, and we may be seeing it in the next 5 years or so.

Q: Are you pursuing more projects in this field?

Yes. Our team who did the first study are going to be continuing to refine and improve the genome. We have a newly funded CIHR grant to continue this work. My new affiliation is with the University of British Columbia’s Botany Department, where I am an Adjunct Professor.

I’m also starting a company, Anandia Laboratories, to attempt to apply some of these genomic findings towards cannabis with improved therapeutic properties. The name Anandia derives from the endocannabinoid molecule anandamide.

Q: Is there more interest in cannabis genomics now than before?

Oh yeah, it’s amazing. For a number of years, I slogged along as kind of a lone voice in the wilderness working on cannabinoid biochemistry. Everyone was always interested in that work on the scientific level, but it’s a controversial plant and you always got the pot jokes whenever I gave a seminar.

But just in the last 6 or 8 months, there’s been a lot of interest in the genomic and biochemical research that I have done. I think there are two things that are driving it: the changes in regulations in Canada, which seem to have spurred a ‘green rush’, and the changes in Colorado and Washington State.

The new U.S. farm bill also allows research on hemp in 9 or 10 states, which they never were able to do before. So everything is sort of coming together, where cannabis was hot before, but now it’s suddenly white hot in terms of a research area.

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