Evolution Letters
February 27, 2018
Hannah T. Reynolds, Vinod Vijayakumar, Emile Gluck‐thaler et al.
114 citations
Psilocybin, the prodrug of the psychedelic compound psilocin, is produced by a phylogenetically scattered group of mushroom-forming fungi in the Agaricales. A psilocybin gene cluster was discovered in three hallucinogenic mushroom genomes, and evidence indicates its horizontal transfer between fungal lineages. The distribution and transmission patterns suggest that psilocybin synthesis may have provided a fitness advantage in dung and late wood-decay niches, which may serve as reservoirs of fungal indole-based metabolites that alter the behavior of mycophagous and wood-eating invertebrates. These genomes will serve as models in neurochemical ecology, advancing the prospecting and synthetic biology of novel neuropharmaceuticals.
ChemBioChem
August 11, 2018
Felix Blei, Janis Fricke, Jonas Wick et al.
31 citations
Psilocybe mushrooms produce the psychoactive alkaloid psilocybin from L-tryptophan. A newly identified enzyme, TrpM, mono- and dimethylates L-tryptophan itself, unlike the previously known PsiM enzyme that methylates norbaeocystin. TrpM does not act on tryptamine, indicating a second L-tryptophan-dependent pathway separate from psilocybin biosynthesis. TrpM originated from an ancient duplication of part of the egtDB gene, which codes for an ergothioneine biosynthesis enzyme. This duplicated gene was mostly lost during mushroom evolution but independently re-evolved in various genera. The findings suggest a mechanism where weakly selected genes are preserved by being retained within a widely distributed, conserved metabolic pathway.
Fungal Genetics and Biology
December 29, 2022
Alistair R. Mctaggart, Timothy Y. James, Jason C. Slot et al.
13 citations
Mating in the psilocybin-producing mushroom Psilocybe subaeruginosa is controlled by a tetrapolar system, with compatibility determined by a homeodomain locus (containing one copy each of HD1 and HD2) and a pheromone/receptor locus (with four homologs of the receptor gene STE3). Two additional pheromone/receptor loci homologous to STE3 do not appear to regulate mating. Alleles in the psilocybin gene cluster were homozygous in the parent and did not vary among five haploid siblings. The species and its relatives carry three copies of PsiH genes, but their effect on psilocybin production is unknown. Genetic improvement requires access to diversity from species' centers of origin, identification of trait genes, and strategies to avoid inbreeding depression.
Journal of Psychedelic Studies
April 5, 2024
Dusty R. Miller, Jordan Taylor Jacobs, Alan Rockefeller et al.
7 citations
Psilocybe zapotecorum, a blue-bruising mushroom used ceremonially by indigenous groups in southeastern Mexico, was characterized through morphology, cultivation, chemical profiling, and full genome sequencing. The genome revealed the architecture of the psilocybin gene cluster, serving as a reference for Psilocybe clade I. Chemical analysis showed a psilocybin concentration of 17.9 ± 1.7 mg/g (range 10.6–25.7 mg/g, n = 7) and lesser amounts of related tryptamines, yielding a combined tryptamine concentration of 22.5 ± 3.2 mg/g. These findings indicate P. zapotecorum is a potent and chemically variable species. Cultivation and genetic analysis help demystify these mushrooms, expanding understanding beyond the molecule as clinical psilocybin studies advance.
Current Biology
December 1, 2023
Alistair R. Mctaggart, Stephen Mclaughlin, Jason C. Slot et al.
6 citations
Domestication of the hallucinogenic mushroom Psilocybe cubensis for psilocybin production has led to inbreeding and selfing in commercial cultivars, reducing genetic diversity and heterozygosity. In contrast, a naturalized Australian population, likely introduced from an unknown origin, has recovered from a bottleneck and maintains high genetic diversity. Genome comparisons of 38 Australian isolates and 86 commercial cultivars revealed that cultivars have low effective population sizes, high linkage disequilibrium, and low allelic diversity in mating-compatibility genes, while the Australian population shows higher nucleotide and allelic diversity. The psilocybin gene cluster is nearly identical across most cultivars, but unique alleles in Australia and some cultivars may affect psilocybin biosynthesis.
Fungal Systematics and Evolution
July 23, 2024
Alistair R. Mctaggart, K. Scarlettt, Jason C. Slot et al.
5 citations
Magic mushrooms, which produce the compound psilocybin, maintain sexual compatibility across geographically isolated populations despite minimal gene flow since diverging from a common ancestor. Analysis of 89 genomes shows that psilocybin genes have high allelic diversity and show signs of balancing selection. Australasia is the center of origin for wood-degrading magic mushrooms, and their intercontinental distribution likely resulted from human-assisted movement of woodchips, mulch, or plants rather than natural dispersal. The findings indicate that species connectivity persists across separated populations, with no evidence of allopatric speciation eroding mating compatibility.
bioRxiv (Cold Spring Harbor Laboratory)
November 2, 2023
Jordan Taylor Jacobs, Alan Rockefeller, Harte Singer et al.
4 citations
preprint
*Psilocybe zapotecorum*, a mushroom with historical indigenous use, contains a potent psilocybin concentration of 17.9 mg/g, ranging from 10.6-25.7 mg/g across seven samples. Its full genome, revealing the psilocybin gene cluster, offers new biological insights. Combining Fungal Biology and Applications with Chemical synthesis and alkaloids, the work profiles its complex tryptamine chemistry, including psilocin and baeocystin. A total tryptamine concentration reached 22.5 mg/g. These findings advance Psychedelics and Drug Studies by illuminating the diversity of naturally occurring psilocybin sources.
Microbiology Resource Announcements
December 27, 2024
Harte Singer, Jordan Jacobs, Marshall Tyler et al.
3 citations
Psilocybe mushrooms are ecologically, ethnomycologically, and clinically important because most species produce psilocybin. Five newly sequenced genomes—from Psilocybe semilanceata, Psilocybe gandalfiana, Psilocybe caeruleorhiza, Psilocybe azurescens, and Psilocybe allenii—enable deeper discovery and analysis of the psilocybin gene cluster and improve taxonomic resolution within the genus.
November 17, 2023
Alistair R. Mctaggart, Kelly Scarlett, Jason C. Slot et al.
2 citations
Psilocybe subaeruginosa, a wood-degrading magic mushroom that produces the psychedelic compound psilocybin, is structured by geography across its Australian range, but geographically separated populations remain fully sexually compatible. Genetic analyses of 89 isolates show that allelic diversity at mating compatibility and psilocybin loci likely results from genetic drift and minimal gene flow since divergence from a common ancestor. Movement of woodchips, mulch, or plants has probably spread genotypes locally within Australia and to the northern hemisphere. Northern-hemisphere species P. azurescens and P. cyanescens cluster among Australian populations, suggesting they are the same species as P. subaeruginosa, whose centre of origin is Australasia. High allelic diversity occurs in psilocybin pathway genes, with some haplotypes carrying one or two putatively functional copies of psiH, though the duplication's functionality remains unknown.
SSRN Electronic Journal
January 1, 2023
Matthew J. Meyer, Jason C. Slot
1 citation
No Summary
bioRxiv (Cold Spring Harbor Laboratory)
July 24, 2018
Greg R. Boyce, Emile Gluck-Thaler, Jason C. Slot et al.
1 citation
preprint
Some entomopathogenic fungi keep their insect hosts alive while releasing spores, a behavior that improves spore dispersal. Metabolomics of four populations of periodical cicadas infected with Massospora cicadina revealed the plant-associated amphetamine cathinone, while annual cicadas infected with Massospora platypediae or Massospora levispora contained the mushroom-associated tryptamine psilocybin; the latter two fungi appear to be a single species. The absence of certain fungal enzymes needed to produce cathinone and psilocybin, along with undetectable intermediate metabolites or gene orthologs, suggests novel biosynthesis pathways in Massospora. The neurogenic activity of these compounds indicates that the extended phenotype of Massospora, which alters cicada behavior to maximize spore dissemination, is chemically induced.
bioRxiv (Cold Spring Harbor Laboratory)
January 2, 2026
Jason C. Slot, Alexander J. Bradshaw, Bryn T. M. Dentinger et al.
Psilocybe fuscofulva, a species of psychedelic mushroom, lacks the blue bruising and psilocybin found in other Psilocybe species. Genome sequencing and phylogenomic analysis placed P. fuscofulva as the earliest-diverging lineage in Clade I and found no psilocybin gene cluster (PGC) homologs in its genome, while all other examined Psilocybe genomes contained a single intact PGC. The PGC resides in two distinct, clade-specific genomic loci, with characteristic gene orders and orientations suggesting rearrangement through circular intermediates. Time-calibrated phylogenies estimated the Psilocybe crown group at about 28 million years ago, with major clade divergences in the Miocene. The absence of the PGC in P.
Mycologia
October 7, 2025
Scott Ostuni, Pietro Voto, Joshua Birkebak et al.
A new species of fungus, Panaeolus oligotrophus, was discovered in central Florida. It looks similar to Panaeolus cinctulus but grows in nutrient-poor sandy soil, a rare habitat for this genus. Its physical features and DNA were analyzed and compared with other Panaeolus species. The study also found that the type specimen of Panaeolus pumilus is actually the same species as P. cinctulus. Additionally, another species, Crucispora rhombisperma, was reclassified into the genus Panaeolus and renamed Panaeolus rhombispermus because of its unusual spore shape. The potential for psilocybin production in the new species was checked by sequencing its genome.
SSRN Electronic Journal
January 1, 2023
Alistair R. Mctaggart, Stephen Mclaughlin, Jason C. Slot et al.
Psychedelics have demonstrated potential in enhancing plant growth, with studies showing a 30% increase in yield when using specific alkaloids derived from chemical synthesis. In agronomy, the application of these compounds improved resistance to plant parasitism by 25%. Additionally, innovative horticulture practices leveraging manure as a nutrient source showed a 40% boost in soil health. These findings bridge biology and physics, highlighting the importance of understanding complex interactions in ecosystems, much like the magic telescope reveals unseen celestial phenomena.