Phylogenomics of the psychoactive mushroom genusPsilocybeand evolution of the psilocybin biosynthetic gene cluster

Abstract

Psychoactive mushrooms in the genus Psilocybe have immense cultural value and have been used for centuries in Mesoamerica. Despite a recent surge in interest in these mushrooms due to emerging evidence that psilocybin, the main psychoactive compound, is a promising therapeutic for a variety of mental illnesses, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five species of Psilocybe, four of which belong to only one of two major clades. We set out to improve the phylogeny for Psilocybe using shotgun sequencing of 71 fungarium specimens, including 23 types, and conducting phylogenomic analysis using 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage arose ~66 mya and diversified ~53 mya. We also show that psilocybin biosynthesis first arose in Psilocybe, with 4-5 possible horizontal transfers to other mushrooms between 40 and 22 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the cluster that corresponds to a deep split within the genus, possibly consistent with the independent acquisition of the cluster. This novel insight may predict differences in chemistry between the two major clades of the genus, providing further resources for the development of novel therapeutics.

Cultivation, chemistry, and genome ofPsilocybe zapotecorum

“…It is also possible that availability of precursors or regeneration or compartmentalization lead to high concentrations of psilocybin in P. zapotecorum . 70–72 Given the brilliant bluing and presence of PsiL and PsiP in this species, high psilocybin is not likely the result of reduced conversion of psilocybin to chromophoric oligomers. The sequence of the P. zapotecorum genome will facilitate direct investigation of all this enzymatic diversity both within and beyond the psilocybin cluster.…”

“…Notable conflict between rpb1 and ITS topologies in Clade II, with limited support, highlights the necessity of examining multiple loci to infer evolutionary relationships in Psilocybe as shown previously and suggests a need for further molecular systematics and/or phylogenomics in the genus. 73,74 The utility of these and other barcode loci will become more apparent as more information is gathered on the population-level sequence variability of P. zapotecorum and as more species' genomes are sequenced. Other chemistries present may add tonal qualities to the experience of these psychedelic mushrooms.…”

Phylogenomics of the psychoactive mushroom genus Psilocybe and evolution of the psilocybin biosynthetic gene cluster

“…Raw short-read sequences for this project have been deposited in the Sequence Read Archive (SRA) and assigned the bioproject number PRJNA904752 and SRA and Biosample accession numbers are reported in SI Appendix , Table S1 . Raw tree files, assemblies, gene prediction files, multiple sequence alignments, and Psilocybe constraint tree are available through Dryad ( https://datadryad.org/stash/landing/show?id=doi%3A10.5061%2Fdryad.tmpg4f52s ) ( 102 ). Any code or specific script requests should be sent to the corresponding author.…”

Los hongos alucinógenos (Psilocybe, Hymenogastraceae) en el desarrollo evolutivo de la consciencia del hombre

“…Estos hongos, a lo largo de la historia, han ocupado un lugar destacado en las tradiciones chamánicas debido a su capacidad para provocar profundos cambios en los estados de consciencia (Swanson, 2018). El estudio específico de especies dentro del género Psilocybe ha permitido adentrarse en los mecanismos bioquímicos y psicológicos detrás de las alteraciones en la consciencia humana (Bradshaw et al, 2024). La presencia de estos compuestos psicoactivos ha sido identificada en especies como P. cubensis, P. semilanceata y otras, evidenciando su potencial para incidir en la percepción y la cognición humanas, generando estados alterados de consciencia que trascienden los límites convencionales de la experiencia humana.…”