How old is Psilocybe?

A lot of progress has been made recently in understanding the genetic basis of psilocybin biosynthesis. Much of this work is being pioneered by Dirk Hoffmeister’s lab, with a significant contribution by Jason Slot’s lab demonstrating the independent acquisition of psilocybin biosynthesis by several species through horizontal gene transfer. My own research has reproduced and refined these results and added new information on the convergent evolution of psilocybin biosynthesis in the genus Inocybe. We now know that psilocybin is synthesized by fungi using four enzymes that catalyze reactions to convert tryptophan to psilocybin (Fricke et al. 2017, Reynolds et al.  2018, Awan et al. 2018). We also know that these four enzymes occur physically next to each other in a cluster (Fricke et al. 2017, Reynolds et al.  2018, Awan et al. 2018), and that this cluster is likely subtelomeric (Awan et al. 2018). This cluster has been acquired by distantly related species through horizontal gene transfer (Reynolds et al.  2018, Awan et al. 2018) and at least in one species through convergent evolution (Awan et al. 2018). We also now know that in addition to psilocybin, at least some species of Psilocybe also manufacture a class of compounds known as ß-carbolines (Blei et al. 2020), chemicals that function to inhibit the enzyme monoamine oxidase (MAO) that normally deactivates psilocybin and related chemicals. This is analogous to the psychedelic cocktail ayahuasca, which combines plants that have ß-carbolines to inhibit the activity of MAO, and plants that have dimethyltryptamine (DMT) that act in the brain similarly to psilocybin (McKenna et al. 1984). So, at least some Psilocybe spp. appear to be like miniature, naturally-occurring nuggets of ayahusaca. And that blue staining reaction so familiar in psilocybin-containing mushrooms? It is formed when cells are broken or senesce, releasing enzymes that link psilocin molecules into short chains (Lenz et al. 2019). These chains of psilocin not only create a chromophore that reflects blue wavelengths of light, but they may serve a protective purpose: like the common plant anti-herbivory flavonoids and polyphenolic tannins, these chains of psilocin may release reactive oxygen in mycophagous insect guts, burning holes in them (Lenz et al. 2019). Like I said, we’ve learned a lot about psilocybin recently. But where did this all start? What is the origin of psilocybin and the organisms that contain them? Although it’s very difficult (or impossible) to reconstruct the past, we can make inferences that at least put some bounds on what is reasonable and what is not. A few questions that were recently posed to me were: how old is Psilocybe? How old is Psilocybe cubensis? And did the acquisition of psilocybin cause them to diversify rapidly? To answer these questions, we need to know how all of the species of Psilocybe are related to each other. And we also need to know some approximate age of things near to them, like using fossils to put some absolute minimum ages on a phylogeny. Unfortunately, the fungal fossil record sucks, so it’s pretty difficult to use fossils to put dates on phylogenies. But we can use secondary dates, i.e. those that are derived from larger studies in which fossil evidence is used. The danger is that using secondary dates can amplify inaccuracies to the point where they are completely meaningless. But, nonetheless, they can be useful to provide some idea about the scale of the time period. Now, there are ~300 species of Psilocybe worldwide, but only a handful have been included in molecular phylogenies (a prerequisite for putting dates on evolutionary trees). The most recent systematic study was completed in 2013 (Ramírez-Cruz et al. 2013). So I borrowed the published phylogeny from this study and ingested it into the ‘ape’ package (Paradis & Schliep 2019) in the statistical software R (R Core Team 2019). I then transformed the branch lengths (the lines connecting the species to each other) to reflect time with a statistical tool called penalized likelihood (I’ll spare you the gritty details), using the divergence time between Psilocybe and the earliest diverging species in the phylogeny to date the origin. This date came from the recent review of divergence times in He et al. (2019). I also calculated a lineages-through-time plot (the red line), which can show departures from a steady birth and death of new lineages, indicating shifts in diversification that may correlated with certain events (e.g., the origin of psilocybin biosynthesis). Now it should be said that patterns like this are probably unreliable, as recently slammed by mathematicians. But it’s fun to look, anyway!


First, the approximate age of Psilocybe (the psychedelic ones) is ~28 million years. This is a ballpark estimate, but I think the important take home is it is measure in millions of years, not thousands or hundreds of millions. They certainly pre-date humans…

Second, there doesn’t appear to be any change in the origin of new lineages in Psilocybe following its origin (presumably coincident with psilocybin biosynthesis). However, it should be emphasized that only a small fraction of the known species of Psilocybe are included here, and this may not be an accurate representation of the entire genus. I think it would be a fascinating investigation to include all species of Psilocybe and get whole genome data from them, wouldn’t it?