Alexander Bradshaw, PhD'22, now postdoctoral researcher at the U and lead author of the study. Credit: Bryn Dentinger
They captured the wider world’s attention as a psychedelic staple in the 60s and 70s. Now, these infamous organisms are at the forefront of a mental health revolution. Psilocybin and psilocin, the psychoactive compounds found in nearly all species of Psilocybe, have shown promise as a treatment for conditions including PTSD, depression, and for easing end-of-life care.
To utilize psilocybin as a therapeutic, scientists need an extensive roadmap of the compound’s underlying genetics and evolution, information that doesn’t exist. Our limited knowledge comes from research on just a fraction of the ~165 known species of Psilocybe. Most psilocybin-producing mushrooms haven’t been studied since they were first discovered—until now.
A team of researchers led by the University of Utah and the Natural History Museum of Utah (NHMU) has completed the largest genomic diversity study for the genus Psilocybe. Their genomic analysis of 52 Psilocybe specimens includes 39 species that have never been sequenced.
Bryn Dentinger, principal investigator. Credit: B. Dentinger
The authors found that Psilocybe arose much earlier than previously thought—about 65 million years ago, right around when the dinosaur-killing asteroid caused a mass extinction event. They established that psilocybin was first synthesized in mushrooms in the genus Psilocybe, with four to five possible horizontal gene transfers to other mushrooms from 40 up to 9 million years ago.
Their analysis revealed two distinct gene orders within the gene cluster that produces psilocybin. The two gene patterns correspond to an ancient split in the genus, suggesting two independent acquisitions of psilocybin in its evolutionary history. The study is the first to reveal such a strong evolutionary pattern within the gene sequences underpinning the psychoactive proteins synthesis.
“If psilocybin does turn out to be this kind of wonder drug, there’s going to be a need to develop therapeutics to improve its efficacy. What if it already exists in nature?” said Bryn Dentinger, curator of mycology at NHMU and senior author of the study. “There’s a wealth of diversity of these compounds out there. To understand where they are and how they’re made, we need to do this kind of molecular work to use biodiversity to our advantage.”