How magic mushrooms evolved

Why does nature produce hallucinogenic compounds? One study set out to uncover the answer...
13 July 2021

Interview with 

Hannah Reynolds, Western Connecticut State University

MAGIC_MUSHROOMS

Three psilocybin mushrooms.

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Almost all psychedelic drugs, even if they’re synthesised in a lab, are based on products found in nature. The question then is - why does nature produce compounds that make you see colours and feel at one with the universe? That’s what an American team set out to answer when they looked into how magic mushrooms have evolved. Hannah Reynolds from Western Connecticut State University told Eva Higginbotham how they did it…

Hannah - There's actually over 200 species of magic mushrooms, and they're scattered all over the world. A lot of them aren't even very closely related to each other. And we were looking to understand - what are the genes that actually make the psychedelic compound psilocybin? And then we wanted to understand - how did these genes evolve?

Eva - And how do they make that psilocybin?

Hannah - So what they're starting with is the amino acid tryptophan. And this is what, if you eat a lot of turkey at the holidays, this is the thing that people say makes you sleepy. It's been debated whether it's just having a giant meal makes you sleepy or if it's really tryptophan... but they start with tryptophan, and then they do basically five chemical transformations, and each of the steps needs a different gene. So those were the genes that we were searching for.

Eva - And how did you go about looking for them?

Hannah - So what we did is we took six mushrooms - three were psilocybin producers, and three were not - and we did genome sequencing of all six. And then what we were looking for is: what are the genes that are shared just between the three magic mushrooms and not the others? That left us with a fairly small pool of genes, because we were ignoring the genes that were just essential for a cell to survive and to grow. And once we had that pool, we looked for the functions, and we basically found this gene cluster. And they also were close to each other on the chromosome.

Eva - How do you know that these genes that you found are the ones that make psilocybin? How can you test that?

Hannah - Great question. So what we did is take the gene sequence and then get the protein from it, and then gave it tryptophan, and it made the product that we expected. We in the United States had to stop there because of regulations that... at the time we were not allowed to create - I think they're called - class 1 drugs. But another team independently found the same genes in a different genome of mushrooms, and they were able to take these enzymes and make psilocybin from them.

Eva - And so the fact that all of these genes were clustered together in the same place of the genome of the mushroom - can we learn anything from that about how those genes might've evolved?

Hannah - Yes. In fungi, when we see that kind of pattern, sometimes that's associated with a history of horizontal gene transfer - gene jumping, if you will.

Eva - I see. So it's not like all the mushrooms across the world all independently were like, "you know what? Let's make some psilocybin." It's more like mushrooms that were next to each other shared the genes required to make psilocybin, and through that mechanism, it spread.

Hannah - Yes. So that was our final step to our paper - looking at what might those environments have been. And the environments that magic mushrooms are usually found in are dung, decaying wood, and mutualistic associations between fungi and tree roots. And it looked like the dung environment was where a lot of these exchanges might've happened.

Eva - And what is the point of these mushrooms making the psilocybin in the first place? What benefit do they get from it?

Hannah - What we think is that, in the environments where the magic mushrooms are growing, they are having to deal with insects, especially insect larvae - that are eating the decaying wood, that are eating the dung, and that maybe even are eating them, especially as they're growing through that resource before they actually make the mushroom itself. So we think that making these hallucinogenic compounds may slow down the insect enough that the mushrooms have a better chance of colonising that material, and actually growing and making a mature mushroom.

Eva - So it's about competition.

Hannah - That's our take on it.

Eva - And what does it do to an insect? If an insect eats a magic mushroom, is it going to get high? Are they like hippies?

Hannah - I think they do. What it feels like to them, I don't know, but I suspect that their brains aren't that different from ours in terms of what this does. Of course insects are living in a more smell-based world than a visual-based world. So I can only speculate, but I would think if they hallucinate, they're not so much getting visuals as maybe olfactory confusion.

Eva - That's amazing!

Hannah - That's a wild guess.

Eva - Smelling hallucinations!

Hannah - And how would I even test something like that? I have no idea. But that's what I imagine.

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