The Cannabis Genome: Part 1
Unlocking The Genetic Code Of Cannabis
Kevin McKernan, the Founder and Chief Scientific Officer at Medicinal Genomics, has spent his career researching and developing various DNA sequencing technologies in both the research and clinical industries. Prior to Medicinal Genomics, he worked on the Human Genome Project at the Whitehead Institute in Cambridge, MA, where he developed the robotics used to automate the process of identifying and mapping all of the genes of the human genome.
But although his accomplishments are many, perhaps his biggest claim to fame was his announcement in August 2011 that his company had “unlocked” the genetic code of cannabis by producing the “largest known gene collection” of the Cannabis sativa plant at more than 131 billion bases of sequence. Previously, only two million bases of Cannabis sequence had been deposited in GenBank, a sequence database provided by the National Center for Biotechnology Information (NCBI).
You see, genetic sequencing is an enormously valuable tool that can be used to elucidate what’s behind the biochemistry of cannabis. It can help us understand the unique biological properties and considerable phenotypic variation in cannabis and the data obtained from sequencing can be used to “DNA fingerprint” specific strains of cannabis and also help improve medicinal quality and improve yields in agriculture.
More importantly though, Medicinal Genomics simultaneously made the bold move to publish its treasure trove of data as open source. This instantly allowed scientists around the world to begin studying the cannabis genome – regardless of whether they had access to the plant or not. (If you’d like to view the material yourself, Medicinal Genomics has published the raw reads from Cannabis sativa on Amazon’s EC2, a public cloud computing service.)
As you know, anti-cannabis laws make it difficult for scientists to breed and study the plant in most countries. In the U.S. alone, marijuana and its extracts including CBD are still classified as Schedule 1 drugs.
But thanks to the publication, researchers for the first time were able to use bioinformatics (the science of collecting and analyzing complex biological data) to freely study the cannabis genome without actually obtaining physical plants.
In one fell swoop, Medicinal Genomics had accomplished three extraordinary things:
- They cracked the genetic code of cannabis
- They eliminated the need for some researchers to obtain physical cannabis and
- They opened up the cannabis genome to a new audience that would be able to legally study it for the first time.
This single event marked the beginning of a new era in cannabis research and was the first step toward truly understanding and enhancing the plant’s therapeutic potential using genomics.
Not long after, a group of researchers from Canada, with help from Medicinal Genomics’ data, released a study on the cannabis sativa genome – setting the wheels in motion for a revolution in cannabis research.
The Cannabis Sativa Genome
Although selective breeding has produced cannabis plants for specific uses, including high THC and high CBD strains, not much is known about how cannabinoid biosynthesis actually works.
What we do know is that cannabinoids are synthesized as carboxylic acids. The key enzymes THCA synthase and CBDA synthase fold the precursor molecules (Cannabigerolic acid) into either Δ9-tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA).
Once THCA or CBDA is heated or smoked, they decarboxylate to their neutral forms. For example, THCA is converted into THC and CBDA is converted into CBD.
However, genetic sequencing has shed new light on the biosynthesis of cannabinoids.
In the study titled, “The draft genome and transcriptome of Cannabis sativa”, Canadian researcher Harm van Bakel and colleagues sequenced the genomic DNA and RNA of THC-rich strain ‘Purple Kush’ and then compared it with the hemp cultivars (and CBD-rich) ‘Finola’ and ‘USO-31’. The results were published in Genome Biology in October 2011.
The authors concluded that THCA synthase, the gene encoding the enzyme that forms THCA, is found in the genome and transcriptome of Purple Kush whereas CBDA synthase dominates in Finola and USO-31.
According to Sam R. Zwenger, PhD, who is the author of The Biotechnology of Cannabis sativa, not only did the authors seek to generate a draft genome, “they also used the sequence data to investigate the genes involved in cannabinoid biosynthesis, analyze the expression patterns of different organs and different flowering stages of the plants, and provide further evidence for the biochemical difference between medical cannabis and hemp. The results of their studies, which greatly expanded the molecular information available on cannabis, also allowed a genetic basis for hemp breeders who aim to improve oil and fiber production in different hemp varieties.”
This provided great insight into the genetic and biochemical differences between cannabis used for therapy and cannabis used for hemp. The transcriptome (total of all RNA molecules) data from flowers, stems, leaves, and roots also allowed for comparison between these different organs as well.
This breakthrough has propelled cannabis genomics by leaps and bounds and has opened up the door to some exciting possibilities. Researchers are now investigating the genes that govern cannabis compounds other than THC and CBD, sequencing other strains of cannabis, tying the differences in DNA to different traits, and even manipulating the DNA sequences of plants in order to produce more desirable end products – like more effective cannabis-driven pharmaceuticals.
The publication now serves as a reference for future transcriptomic investigations and offers an excellent starting point for cannabis biotechnology research. Today, the race is on to see what the next generation sequencing pipeline will produce.
We continue this discussion in part 2 of The Cannabis Genome.
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