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The genomic analysis of 52 Psilocybe specimens includes 39 species that have never been sequenced. Psilocybe arose much earlier than previously thought — about 65 million years ago — and the authors found that psilocybin was first synthesized in mushrooms in the genus Psilocybe. Their analysis revealed two distinct gene orders within the gene cluster that produces psilocybin. The two gene patterns correspond to an ancient split in the genus, suggesting two independent acquisitions of psilocybin in its evolutionary history. The study is the first to reveal such a strong evolutionary pattern within the gene sequences underpinning the psychoactive proteins synthesis.