Scratching the genetic surface of poisonous mushrooms
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The Walton lab has sequenced the genomes of two species of Amanita mushrooms which are responsible for the majority of fatal mushroom poisonings. The results have extended previous observations about how the mushrooms produce their deadly poisons, while surprising the researchers with the versatility displayed in their DNA.
The “Death Cap” and the “Destroying Angel”
Dr. Jonathan Walton, Professor at the PRL, is fascinated by how poisonous mushrooms produce toxins. “These poisons that hurt or kill us are cyclic peptides, basically smaller, simpler proteins. Because they are ring-shaped and do not have any free ends, it is hard for our bodies to latch on to them in order to break them down or to repel them.”
“So the toxins get into our blood streams and cells very easily.”
Walton’s genetic study focused on two Amanita species, the “Death Cap,” which grows all over Europe and the US west coast, and the “Destroying Angel,” native to Michigan. “We actually did a partial DNA sequence of the two mushrooms 10 years ago, and as sequencing has gotten faster and cheaper, we were able to complete the project recently.”
As Walton and his colleagues expected, the data revealed the genes responsible for several of the known harmful cyclic peptides. But, to their surprise, they discovered that the mushrooms have the potential to synthesize many more cyclic peptides than previously known, potentially billions, through one production platform – the equivalent of producing an unlimited number of car models on a single assembly line.
“Imagine you have 10 different lego bricks,” Walton says. “There are so many ways you can put them together. Cyclic peptides are assembled just like legos, each one made of 8-10 out of a total of 20 possible amino acids. If you scramble these components, you can make thousands, millions, even billions of these molecules through that one molecular platform.”
And so far, Walton and his colleagues have already discovered three previously unknown cyclic peptides. “We found a new gene family closely related to the known toxic cyclic peptides. So we predicted, correctly it turns out, that some of those genes produce similar molecules.”
Many cyclic peptides are not poisonous, however. And even though the researchers are still beginning to understand the power of this flexible production platform, they can already picture future adaptations for human use.
“Various cyclic peptides are already known to be important drugs against tuberculosis, drug-resistant Staphylococcus, and cancer. Up till now, the only studies done with this type of mushroom extracts have been looking for things that kill mammals.”
“By harnessing the Amanita system, we can imagine a less crude and potentially more effective way to synthesize a large pool of new nontoxic cyclic peptides in the lab, with potential pharmaceutical uses.”
The genetic data also revealed how scientists are just scratching the surface of how complex the mushroom kingdom is.
Species are usually identified through universally accepted locations in DNA that function like barcodes. Different species have unique barcodes.
One of the mushrooms analyzed, Amanita bisporigera (“Destroying Angel”), is native to the midwest and East coast of North America, including Michigan. The genetic barcode in this case was 92% identical to another specimen of A. bisporigera mushroom sequenced in an earlier study.
“In comparison, human and chimpanzee genomes are 95% identical,” Walton adds, “yet they are not considered the same species at all. So, by any measure we currently have, these two mushrooms are different species, even though they look identical and we currently call them by the same name.”
Furthermore, the two specimens of A. bisporigera were found to have the genetic capacity to make almost entirely different cyclic peptides. Walton thinks this indicates that the cyclic peptide repertoire of these mushrooms is evolving very quickly, probably because they grant a strong adaptive advantage to the mushrooms in their environment.
“In a sense, this study tells us how little we know about classifying organisms and how advances in DNA sequencing are changing our ideas about how we label things. It is going to require many years of work to fully identify the differences between these two mushrooms.”