Phylogenomics of the psychoactive mushroom genus Psilocybe and evolution of the psilocybin biosynthetic gene cluster
Proceedings of the National Academy of Sciences – January 09, 2024
Source: OpenAlex
Summary
The psychedelic alkaloid psilocybin, driving Psychedelics and Drug Studies, first evolved in the mushroom genus Psilocybe around 67 million years ago. Evolutionary biology indicates its biosynthetic gene cluster transferred horizontally 4 to 5 times to other fungi between 40 and 9 million years ago. Using 71 fungal metagenomes, Phylogenetics of 2,983 gene families reveals Psilocybe's deep Biology. Two distinct psilocybin gene cluster arrangements correspond to major clades, suggesting independent acquisitions of this alkaloid's chemical synthesis, impacting Fungal Biology and Applications.
Abstract
Psychoactive mushrooms in the genus Psilocybe have immense cultural value and have been used for centuries in Mesoamerica. Despite the recent surge of interest in these mushrooms due to the psychotherapeutic potential of their natural alkaloid psilocybin, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five of ~165 species of Psilocybe , four of which belong to only one of two major clades. We set out to improve the phylogeny of Psilocybe using shotgun sequencing of fungarium specimens, from which we obtained 71 metagenomes including from 23 types, and conducting phylogenomic analysis of 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage of Psilocybe arose ~67 mya and diversified ~56 mya. We also show that psilocybin biosynthesis first arose in Psilocybe , with 4 to 5 possible horizontal transfers to other mushrooms between 40 and 9 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the biosynthetic gene cluster that corresponds to a deep split within the genus, possibly a signature of two independent acquisitions of the cluster within Psilocybe .