Proceedings of the National Academy of Sciences of the United States of AmericaJan 9, 2024

Evolutionary history of the psychedelic mushroom group Psilocybe and the genes that produce psilocybin

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Updated Jan 19, 2026

Abstract

A comprehensive phylogeny of the genus Psilocybe was generated using 71 metagenomes and 2,983 single-copy gene families.

Molecular clock analysis indicates the stem lineage of Psilocybe emerged approximately 67 million years ago, with diversification occurring around 56 million years ago.
biosynthesis is suggested to have first developed in Psilocybe, with 4 to 5 possible instances of gene transfer to other mushroom species between 40 and 9 million years ago.
Distinct gene orders within the psilocybin biosynthetic gene cluster correspond to a significant evolutionary split within the genus, indicating potential independent acquisitions of the biosynthetic cluster.

Simplified

Psychoactive mushrooms in the genushave 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 , 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, four of which belong to only one of two major clades. We set out to improve the phylogeny ofusing 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 ofarose ~67 mya and diversified ~56 mya. We also show that psilocybin biosynthesis first arose in, 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 Psilocybe Psilocybe Psilocybe Psilocybe Psilocybe

Key numbers

87%

Gene Recovery Rate

Single-copy genes recovered across all samples.

67 mya

Divergence Time Estimate

Estimated stem age of the lineage.

40 species

Species Representation

Total species represented in the phylogenomic analysis.

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Funding

Competing interests

Competing interests statement:The authors declare no competing interest.

PubMed

Evolutionary history of the psychedelic mushroom group Psilocybe and the genes that produce psilocybin

Abstract

Key numbers

Full Text

Funding

Competing interests

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Abstract

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Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

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