The one that abstained: Psilocybe fuscofulva genome suggests two recent origins of the psilocybin gene cluster in Psilocybe
OpenAlex – January 02, 2026
Source: OpenAlex
Summary
Psilocybin, the psychoactive compound defining the *Psilocybe* genus, surprisingly originated twice. Genomics and Phylogenetic Studies of multiple *Psilocybe* genomes (four newly sequenced) revealed *Psilocybe fuscofulva* (a *Psilocybe sensu stricto* lineage) lacks the psilocybin gene cluster (PGC) and psilocybin. Analyzing 100 gene orthologs across the phylogenetic tree, the PGC emerged independently in two distinct Clades (I and II) around the Miocene epoch. This evolutionary biology suggests horizontal gene transfer, not a most recent common ancestor, drove this lineage's genetics, impacting Psychedelics and Drug Studies.
Abstract
Abstract Production of the psychoactive compound psilocybin is a defining feature of the genus Psilocybe , commonly referred to as “psychedelic mushrooms”. However, Psilocybe fuscofulva is a striking exception within Psilocybe sensu stricto as it lacks the stereotypical blue bruising characteristic of the genus, and psilocybin has not been detected in the species.To investigate the evolutionary events leading to differential psilocybin production among Psilocybe species, we produced genome assemblies two P. fuscofulva strains, one Psilocybe polytrichoides strain, and one Psilocybe tampanensis strain, complemented by reannotated public genomes and metagenome-derived assemblies from fungarium specimens. This sample represents both major Psilocybe clades (Clade I and Clade II) and the most closely related genera. Phylogenomic analysis based on 100 single-copy orthologs curated for high branch support strongly placed P. fuscofulva as the earliest-diverging lineage in Psilocybe Clade I. No psilocybin gene cluster (PGC) homologs, whether clustered or dispersed, were identified in P. fuscofulva , whereas a single intact PGC was present in all other examined Psilocybe genomes. The PGC resides in two distinct, clade-specific genomic loci: one conserved in Clade I and another in Clade II, each displaying characteristic gene orders and orientations consistent with rearrangement through circular intermediates. Time-calibrated phylogenies estimated the Psilocybe crown group at approximately 28 million years ago, with major clade divergences occurring in the Miocene. The absence of the PGC in P. fuscofulva , together with clade-specific structural conservation and the lack of remnant sequences at alternate loci, supports two independent origins of the PGC within Psilocybe : one in the ancestor of Clade II and a subsequent origin in Clade I following divergence from P. fuscofulva , most likely via horizontal gene transfer (HGT). Gene phylogenies provide weak support for transfer from Clade I to Clade II, although broader sampling is required for confirmation. These results constrain the timeframe of PGC emergence and dispersal to the Miocene, implying rapid HGT events possibly driven by ecological pressures in expanding grassland ecosystems. This study challenges the assumption of an ancestral psilocybin pathway in Psilocybe and its close relatives and underscores multiple recent acquisitions of the PGC that suggest it is an ecologically important metabolic trait in psychoactive fungi.