Hello! I decided to share an essay I wrote for my Environmental Physiology class as I found the topic rather interesting.
The prompt: “Discuss the evolution of a toxin or toxin delivery mechanism in an animal, plant, or other group of organisms. Explain the potential adaptive value of the toxin and discuss its potential cost to the organism.”
A Brief Evolutionary Look at Psilocybin
For thousands of years, humans have been taking advantage of fungi and their various properties for use in food, medicine, spirituality, and other aspects of life and culture. It was found that as far back as Pre-Columbian Mesoamerica, people utilized mushrooms with hallucinogenic properties as a method of communication with gods and in religious ceremonies (Kôhler, 1976). In recent times, the chemicals produced are being investigated for potential pharmaceutical applications, such as in treatment of psychological disorders and chronic pain (Kupferschmidt, 2014). Of course, the fungi did not develop these compounds for human enjoyment but instead evolved them for their own uses. Since creating a toxin requires energy and resources, the benefits the fungi would derive must outweigh the cost for it to be evolutionarily retained. The production of psilocybin acts as a defense against predators and for use in competition for resources, and ecological niche permitting, the genes involved can be passed to other fungi through a variety of methods, such as horizontal and vertical gene transfer.
Psilocybin, as mentioned above, is a chemical commonly found in hallucinogenic mushrooms. When dephosphorylated in the digestive tract and liver of humans, it becomes psilocin, which then has the ability to pass the blood-brain barrier (Dinis-Oliveira, 2017). From there, it can be turned into a variety of metabolites in which can be either further used or excreted. If used, it binds with serotonin receptors, or 5-HTRs, in the brain and causes a wide variety of effects. Each person’s experience will vary, but some common effects include hallucinations of any or a combination of senses, euphoria, drowsiness, unusual thought patterns, muscle weakness and poor coordination, and dilated pupils (U.S. Department of Justice Drug Enforcement Administration, 2017). In other non-bacterial organisms, the effects can range from minor behavior change to death (Hessling, 2017; Mansour, 1979).
Researchers found neurotrophic substances in nearly three hundred species of fungi, with nearly two-thirds of them containing psilocybin and its metabolites (Guzmán, Allen, and Garrtz, 2000). The Psilocybe genus notably contains most of the psilocybin-containing mushrooms, with over 120 species, but the chemical is also found in mushrooms of entirely separate families as well (Guzmán, Allen, and Garrtz, 2000). With this one chemical found in many scattered and distantly related species, a look into its evolutionary history may provide answers as to how this is possible.
In a study done regarding the Inocybaceae family, researchers tried to find whether muscarine, a deadly toxin that works on acetylcholine receptors in humans, and psilocybin individually have common ancestors and lineages that could provide clear answers as to how the traits evolved (Kosentka, et al., 2013). Although the presence of psilocybin in species of Inocybaceae is not as common as in the family Hymenogastraceae, which contains the Psilocybe genus, two instances of independent evolution for the chemical were seen over the five psilocybin-positive assayed species. In addition, a plethora of cases of muscarine evolution occurred, showing that the chemical has left and re-entered fungi lineages on multiple occasions (Kosentka, et al., 2013). Psilocybin-positive Inocybaceae species, though, do not contain muscarine, and it is believed the two chemicals are “mutually exclusive” of one another (Kosentka, et al., 2013). Psilocybin is also relatively younger than muscarine in the Inocybaceaes’ phylogenetic tree. Though the lack of muscarine in psilocybin-positive species may appear to suggest that the transition from muscarine to psilocybin in those five species is genetically correlated, their biosynthetic pathways and ancestry suggest otherwise. In tested species, muscarine relies on the amino acid glutamic acid as precursor, while psilocybin uses the amino acid L-tryptophan (Bu’Lock, 2007; Fricke, Blei, and Hoffmeister, 2017). The rest of the biosynthetic pathways utilize different enzymes and processes as well. Additionally, one lineage in Kostentka’s study shows the most recent ancestor of a psilocybin-positive species containing muscarine, while the other lineage had a significant number of muscarine-negative recent ancestors (Kosentka, et al., 2013). This suggests that psilocybin biosynthesis is not directly related to other toxin production and was evolved in Inocybaceae in a different manner. Possible explanations include it being unnecessary and costly for the mushrooms to produce two toxins, or the use of psilocybin is preferred for those given species due to environmental pressures.
Although how the psilocybin in Inocybaceae originated is not confirmed, similar pop-ups of psilocybin production between other distantly related species were found to have used horizontal gene transfer (Reynolds, et al., 2018). Unlike vertical gene transfer, where genes linearly flow from parent to child or ancestor to descendant, horizontal gene transfer occurs when an organism passes its genetic material to another organism in a different manner, such as through an intermediate species like a virus or bacteria. In a study looking at psilocybin-producing genes, sampled fungi preferred the transfer of gene clusters based on ecological niche over close genetic relatedness (Reynolds, et al., 2018). Researchers identified similar to identical gene clusters mostly in fungi that had overlapping environments (Reynolds, et al., 2018). This demonstrates that some habitats and roles produce more of a need for psilocybin than others. Note, though, in clades such as that of Psilocybe, where a majority of the mushrooms are psilocybin-positive, vertical gene transfer is still the primary method of gene transfer. Rather, it is the wide range of distantly related species with psilocybin-negative ancestors containing similar biosynthetic pathways that is rather uncanny when without an explanation. Although not yet studied, horizontal gene transfer may be how the previously mentioned Inocybaceae evolved their psilocybin genes, as well.
Seeing as how a wide range of species evolved the same mechanism, the hypothesis that psilocybin plays a beneficial role in mushrooms’ lives and fitness is highly supported. Like other toxin-producing organisms, psilocybin may be a form of defense against animals, plants, and even other fungi that may try to consume it. In a study done on helminths, many of which live in soil and partake in fungivorism, it was found that the use of hallucinogenic indoleamines similar to psilocybin on serotonin receptors caused reduced movement up to paralysis and behavior changes (Mansour, 1979). Serotonin plays different roles in each organism, so things like elevated mood and bowel movements in humans differ greatly from decreased movement in helminths or aggression in, say, Mediterranean field crickets, among other things (Mansour, 1979; Hessling, 2017). Similarly, helminths contain acetylcholine receptors, and when binded with an agonist, such as nicotine in Mansour’s study, complete paralysis occurred (Mansour, 1979). The previously mentioned muscarine is also an acetylcholine agonist, again providing a potential explanation for why the evolution of chemical biosynthesis is favoured in ecosystems where predators with high toxin vulnerability exist. A difference to note, though, is that nicotinic and muscarinic acetylcholine receptors have slightly different functions and affect different species differently, so the evolution of toxins within fungi is most likely specialized to their current predator (Jones and Sattelle, 2010). The disappearance of a toxin may suggest a change in predator, predator evolution in response to the toxin, or that a different defense mechanism is preferred, while conversely for the introduction of a toxin.
While defense from being consumed is considered a primary reason for psilocybin production, fending off competition and capturing prey is also plausible. The species Pleurotus ostreatus, an oyster mushroom not known to contain psilocybin, will capture and consume helminths, specifically nematodes, if in a medium with poor nitrogen content (Renahan & Sommer, 2020). They produce a toxin which paralyzes the helminths, allowing them to easily begin their consumption. The toxin produced is believed to be trans-2-decenedioic acid, which is a dicarboxylic acid similar to the amino acid glutamic acid (Kwok, et al., 1992). Given the diverse range of mushrooms that can produce psilocybin, it is possible that one/many species could benefit from said toxin by allowing it to capture prey. More research would need to be conducted, but seeing as psilocybin can cause paralysis and distorted behaviours, similar to the trans-2-decenedioic acid, this is not an unreasonable possibility.
Competition in a shared niche can also drive an organism to produce a toxin. In a study done on organisms that live in dung and wood decay microenvironments with Psilocybe cubensis, bacterial species, soil microbes, C. elegans, and brine shrimp were tested for psilocybin toxicity (Meyer, 2017). Brine shrimp had the highest mortality, followed by soil microbes, while C. elegans and the bacterial species had significantly lower mortality rates (Meyer, 2017). Behavioral changes, though, were not recorded, so although the C. elegans, which are helminths, did not typically die from psilocybin exposure, other effects could have occurred. A possible explanation for the high mortality of the brine shrimp, which are arthropods like insects, and soil microbes could be that they are significantly more deleterious to the P. cubensis than the selected bacterial species and C. elegans (Meyer, 2017). Various arthropods feed on decaying substances, so while the researcher involved in the study suggests the psilocybin may be a defense against fungivorism, it could also be used to stop organisms that eat general vegetation/decay where the fungi grow.
Producing a toxin can be costly for an organism, so in order to keep the trait, the benefit must cause higher fitness than the cost reduces. Although the exact costs faced by the fungi have not been extensively studied, it still takes energy and resources to produce psilocybin. Additionally, when a toxin is no longer useful, species have been seen to lose the trait. Seeing as muscarine in Inocybaceae disappeared many times, it can be assumed that when not as strongly needed, the fungi may lose traits and even possibly regain them if later available. It is plausible that species use this method to keep psilocybin-production costs in check, as well. This is further supported when keeping in mind the fungi’s abilities to participate in horizontal gene transfer, but once again, this is speculation and further research would be required (Reynolds, et al., 2018).
Psilocybin, a chemical structurally similar to serotonin, is seen in a wide variety of mushroom species. It is believed that mushrooms evolved this chemical due to possible benefits, such as defence against fungivores and competitors. Since such distantly related species have the biosynthetic genes needed, horizontal gene transfer with a preference for ecological niche rather than close genetic relatedness was most likely utilized to transfer it between the families (Reynolds, et al., 2018). Although more research would need to be conducted on its role in some specific niches, it can be said that the powerful effects it has on other organisms in its shared environment must mean there is a significant purpose for the mushrooms to produce it (Meyer, 2017). Additionally, given psilocybin’s similarities to serotonin and its wide range of effects on humans and animals, it holds potential for pharmaceutical implementation.
Happy reading,
-Beppa
*This is a republished post due to a domain change.*