Horizontal gene cluster transfer increased hallucinogenic mushroom diversity.
Secondary metabolites are a heterogeneous class of chemicals that often mediate interactions between species. The tryptophan-derived secondary metabolite, psilocin, is a serotonin receptor agonist that induces altered states of consciousness. A phylogenetically disjunct group of mushroom-forming fungi in the Agaricales produce the psilocin prodrug, psilocybin. Spotty phylogenetic distributions of fungal compounds are sometimes explained by horizontal transfer of metabolic gene clusters among unrelated fungi with overlapping niches. We report the discovery of a psilocybin gene cluster in three hallucinogenic mushroom genomes, and evidence for its horizontal transfer between fungal lineages. Patterns of gene distribution and transmission suggest that synthesis of psilocybin may have provided a fitness advantage in the dung and late wood-decay fungal niches, which may serve as reservoirs of fungal indole-based metabolites that alter behavior of mycophagous and wood-eating invertebrates. These hallucinogenic mushroom genomes will serve as models in neurochemical ecology, advancing the (bio)prospecting and synthetic biology of novel neuropharmaceuticals.