Botulinum toxin found in new, common bacteria

Clostridium botulinum, Photo: Eye of Science

Evolutionarily, horizontal gene transfer between bacteria is generally not so groundbreaking. In this case however, it’s a little more newsworthy. A lot of bacteria carry plasmids, which are mobile little DNA structures that are not part of the bacterial chromosome and can be transferred to other bacteria. Often plasmids contain genes that may provide some selective advantage (otherwise why bother keeping them?), such as a toxin or an antibiotic resistance gene. Enterococcus happens to be frequent plasmid-carrier, which makes it an especially good candidate for frequent horizontal gene transfer. But first, Clostridium. 

Clostridum is an especially fun group of bacteria including some really famous germs:

  • C. tetani (Tetanus),
  • C. difficile (the bacteria in your gut that gives you stomach issues after you take antibiotics as it swarms in on all the spaces other bacteria used to be, before they were killed by antibiotics),
  • C. perfrinigens (perhaps the nastiest of all, gas gangrene),
  • the less famous C. sordelli (which is a rare–but plenty horrific, pregnancy and abortion-associated infection almost always resulting in death by toxic shock syndrome)
  • And of course, C. botulinum, the primary culprit of botulism.
What is Botulinum toxin?

C. botulium is known for releasing botulinum toxin (BoNT), a toxin which interferes with the release of the neurotransmitter—acetylcholine, from axon terminals at the neuromuscular junction resulting in flaccid paralysis (you can’t breathe).

The toxin (a protein) works by binding to receptors at the neuromuscular junction. It is then taken into the cell by receptor-mediated endocytosis. A conformational change occurs inside the early endosome (due to a pH change). A piece of the protein (the light chain) is translocated to the cytosol when another piece of the protein (the heavy chain) forms a sort of channel. This light chain can then cleave these important complex-forming “SNARE” proteins, which are vital to normal vesicular transport and neurotransmitter (which in this case is acetylcholine) release. So without these SNARE proteins, the little acetylcholine vesicles don’t get to where they need to be. In normal neurotransmitter release, SNARE proteins would work to tether the vesicles to the membrane so the cell and vesicle membranes could fuse to allow the release of neurotransmitters.

Screen Shot 2018-02-02 at 11.12.42 PM
Visualized by me on Pymol- PDB file: 3BTA, BoNT, Serotype A. You too, can play around with it in pymol/swissPDB/Chimera/some other visualizer!

Botulinum toxin is the deadliest toxin known requiring just two billionths of a gram to kill someone person. It’s so dangerous that when type H (one serotype of the toxin) was discovered and failed to be controlled by typical botulinum antibodies, the type H toxin became the only example of a genetic sequence that was hidden from public databases due to security concerns. I say “may be” because how would we really know?

Not just in C. botulinum anymore

While we used to take comfort in knowing we could probably avoid Clostridium botulium by just avoiding puffed up canned food, rotten meat, and organic honey, that may no longer be the case. For the first time, the botulinum toxin has been found in a completely different (and very distantly related) bacteria: Enterococcus.

This new variant of the toxin called BoNT/En, was found in South Carolina, in an E. faecium strain isolated from cows. And it wasn’t just the toxin that was found. Several associated proteins that prevent the toxin from being degraded were also found. That being said, the BoNT/En variant didn’t give the cow it was found in, botulism, and it was not actually very harmful initially in mice. Researchers had to manipulate the toxin to better target mice before it was able to actually kill them (I know. Trying to give mice botulism is upsetting, and the reason why I stick to cells and microbes for my research). They are testing the toxin on human neurons to see how toxic it is to humans.


What makes this particular jump so terrifying is that Enterococcus is a highly abundant group of bacteria all over our bodies. It is ubiquitous in animals and actually a significant human pathogen. E. faecium is a very hardy bacterium easily evolving antibiotic-resistance and actually pretty difficult to get rid of in hospital surfaces. The thought of a dangerous neurotoxin being easily transferred to a ubiquitous and antibiotic-resistant bacteria is somewhat frightening. That being said, plasmids containing incredibly dangerous neurotoxins would likely need to provide a selective advantage to the host to stick around (and it’s possible in E. faecium’s case, it could even provide a slight disadvantage). BoNT can be carried in a bacteriophage, in a plasmid, or on a chromosome, but carrying a sizable gene cluster you don’t need in evolution has usually resulted in a “you don’t use it, you lose it” outcome. As plasmids by themselves are slightly disadvantageous to carry, what keeps them around is any selective advantage the genes they contain provide.

Where did these toxins come from?

Researchers found that the homolog of BoNT in Clostridium, seemed to be a flagellin gene. These flagellins contain collegenase which breaks down peptide bonds in collagen, so they are also a proteolytic toxin family like the Clostridia neurotoxins. They believe that the neurotoxin and adjacent genesevolved from an ancestral collagenase-like gene cluster.  This gene cluster was likely duplicated and evolved separately to become the BoNT we know today.

My case against Botox: amazing, but maybe take it easy?

Botox can be useful for treating cerebral palsy, urinary incontinence, wrinkles, sweating, spasms, headaches, and tinnitus. While no one’s reportedly died from cosmetic Botox use (presumably because people are probably extra careful with such a terrifying substance), there’s a risk of the toxin spreading beyond the injection site and causing respiratory paralysis. While ordinarily I’m totally accepting of people’s desire to do strange or expensive things in the name of beauty, my (probably illogical) fear is that all it takes is one new guy thinking a smudged decimal point is a comma and you’re dead of flaccid paralysis.

Consider that a muscle with a cut nerve will quickly result in atrophy which will definitely make you look worse, not better. Not using your face muscles isn’t going to prevent you from wrinkling because the issue is not the muscles, but the soft tissue decline that comes with age. Neuromodulators like Botox are very expensive, usually require a high enough dose to actually be effective and wear off in a few months, meaning you would have to get several injections a year to stay smooth and shiny, and the repeated injections are when people tend to see more negative side effects and require a higher dose.

Paralyzing muscles over and over again is not great for you long-term so maybe try sunscreen, a nice skincare routine, and drink plenty of water instead? Mistakes happen, people misplace decimal points, I’d rather not be near it personally. Just a friendly PSA to remind you to definitely do your research if you want to mess around with botulinum toxin!


  1. Sicai Zhang et al. Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium. Cell Host and Microbe, 2018
  2. P.K. Nigam, Anjana Nigam. Botulinum Toxin. Indian Journal of Dermatology. 2010 Jan-Mar; 55(1): 8–14.
  3. Doxey AC, Lynch MD, Müller KM, Meiering EM, McConkey BJ. Insights into the evolutionary origins of clostridial neurotoxins from analysis of the Clostridium botulinum strain A neurotoxin gene cluster. 2008.

Cryptococcus — (r)evolutionary genius


If you’re in the market for a particularly fun fungus to tell your friends about, I’d suggest the pathogenic yeast, Cryptococcus.

Cryptococcus is primarily known for causing Cryptococcal meningitis—a leading cause of death in AIDS patients. This is Cryptococcus neoformans, which, while more common really only infects the immunocompromised. Its cousin, Cryptococcus gatti, frequently infects immunocompetent, healthy individuals and is an important emerging pathogen. Weirdly enough, C. gatti infections all seem to come from trees. The fungal pathogen has dispersed all over the world surprisingly, scientists believe, due to continental drift. In the past few years, there’s been large outbreaks of the less common Cryptococcus gatti in the Pacific Northwest/Canada and South Africa.

Sex has something to do with it

Cryptococcus needs a lot of sugar to reproduce, particularly inositol which is all over the human brain and spinal cord which is probably why Cryptococcus is known for causing meningitis. Cryptococcus (depending on the species) has between about 6 to 12 genes involved in inositol transport while most fungi have only about two. While inositol is needed for reproduction and results in higher virulence, which mating type the fungus is may also play a large role in pathogenicity.

In yeasts there are two mating types, MATa and MATα. MATα strains are able to produce an extensive hyphen phase in the haploid state called monokaryotic fruiting. All the clonal C. gattii VGII (or C. deuterogatti) that have been infecting people have notably been from the same mating type: Matα. MATα strains are capable of same-sex mating which could be the origin for the outbreak around Vancouver. In C. neoformans, MATα strains which have their own genes specific to that mating type, are associated with higher virulence (but there’s no evidence of this with C. gattii). 

From Springer 2010, isolations of C. gatti from human clinical, veterinary, environmental sources. Underestimation of actual prevalence.

Researchers found that several isolated C. deuterogatti strains contained mutations in MSH2, one of the genes involved in mismatch repair (genes that fix DNA replication errors). The human homologous MSH2 gene has the same effect where humans with mutations in MSH2 can have Lynch Syndrome, where they’re prone to various cancers.

The mutations in MSH2 in fungi were tested and resulted in their genomes mutating at a faster pace but growing at the same rate as wildtype Cryptococcus strains. When exposed to stressful conditions however, such as antifungals like rapamycin and FK506, the mutant strains rapidly took over as they could quickly acquire resistance to drugs. In the process of acquiring drug resistance the strains actually decreased in virulence and were significantly weakened compared to the outbreak strains.

So the hypermutators are much more fit in stressful conditions and can rapidly outcompete the wildtype strains, however they make a less fit pathogen without significant selective pressures present. This brings up an interesting question in host-pathogen evolution—what kind of genome makes for an ideal pathogen? Fungi in general are lousy pathogens, especially in people. Certainly white-nose syndrome in bats and chytrid fungus in amphibians have devastated populations but there aren’t a whole lot of “in between” fungal pathogens. Having a lower mutation rate than bacteria or viruses contributes to their easiness to treat. While in bacteria a hypermutator strain rapidly evolving drug resistance usually sounds like a bad thing, in this case hypermutator strains taking over would at least lower the virulence and fitness of the fungus as a pathogen.

It’s even worse in men

As is the case with many pathogens, there is an increased incidence of the disease in men and when it does appear mortality rates are significantly higher in men. C. neoformans isolates from females had a slower growth rate and released more capsular glucoronoxylomannan (GXM), (a virulence factor and immunosuppressant). Testosterone was associated with higher levels of GXM release while 17-β estradiol was associated with lower levels and slower growth rate. Furthermore, macrophages from females were better at fighting off C. neoformans than macrophages from males which were more damaged from the infection. This may explain why infections are more common in men.

While Cryptococcus neoformans has been a common issue for a while, Cryptococcus gatti has only recently emerging as a prominent pathogen, which scientists believe could be the result of climate change. These Cryptococcus infections infect healthy people and are fatal if left untreated.


  1. The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. Y. Chang-L. Penoyer-K. Kwon-Chung – Proceedings of the National Academy of Sciences – 2001
  2. The Role of Host Gender in the Pathogenesis of Cryptococcus neoformans Infections. Erin Mcclelland-Letizia Hobbs-Johanna Rivera-Arturo Casadevall-Wayne Potts-Jennifer Smith-Jeramia Ory – PLoS ONE – 2013
  3. Highly Recombinant VGII Cryptococcus gattii Population Develops Clonal Outbreak Clusters through both Sexual Macroevolution and Asexual Microevolution. R. Billmyre-D. Croll-W. Li-P. Mieczkowski-D. Carter-C. Cuomo-J. Kronstad-J. Heitman – mBio – 2014


Cretaceous pterosaur diversification and extinction

Artist: Mark Witton

Few things are as disappointing as learning that no pterosaurs survived the K/Pg extinction. This has always been especially hard for me to emotionally accept due to their immense diversity. The typical explanation usually told is that they were wiped out with the non-avian dinosaurs after the chicxulub impact, and that they were barely alive by that time anyway because all the birds had filled up the flying niches. However recent evidence indicates that pterosaurs actually were doing very well up until 65 million years ago. Why they went extinct may have nothing to do with birds or a failure to diversify. Serial size reduction allowed for smaller pterosaurs to survive through other extinctions. Reaching sexual maturity before being fully grown allowed for smaller hatchlings maturing more quickly, allowing for more reduction in size by accelerating evolution somewhat. So if there were smaller pterosaurs at the end of the Cretaceous, AND pterosaurs have previously proven to be capable of relatively rapid phylogenetic size decreases, why did no pterosaurs survive?

The Cretaceous is more known for its giant, “small-plane sized” pterosaurs (Arambourgiania, Quetzalcoatlus, and one that’s been in the news more recently for “terrorizing” Transylvania: Hatzegopteryx). For background pterosaurs are split into two major suborders, with Rhamphorhynchoids being a paraphyletic group characterized by having teeth, long tails, and a cruropatagium that stretched between the feet (like how bats have it). Most were small and lacked bony head crests. They appeared in the Triassic and went extinct during the Cretaceous though there is no strong evidence to indicate they were outcompeted by pterodactyloids which is a common assumption.

Pterodactyloids, the other suborder, did not appear until the late Jurassic and were much more successful and diverse in the Cretaceous. While all pterosaurs are outstanding creatures, the pterosaurs this post is concerned with would all be pterodactlyoid members.

Rhamphorhynchoid on left, Pterodactyloid on right

No fossils of pterosaurs have been found from after the K/Pg extinction (and I don’t believe there ever will be 😦 ). But while there are certainly no pterosaurs alive today, there is a lot of evidence indicating that pterosaurs were actually quite diverse even at the end of the Cretaceous, and that some were even very small. The discovery of small pterosaurs from the late Cretaceous does seem to indicate that the reason for their clade’s total extinction was not simply because they were just “too large.”

Small pterosaurs may have been more abundant in Cretaceous than previously thought

A small azhdarchoid (azhdarchoids being the most recent common ancestor of Quetzalcoatlus and Tapejara, and all its descendents) pterosaur was discovered from the Campanian Northumberland Formation of British Columbia. With an estimated 1.5m wingspan, the pterosaur specimen is described as being about the size of a large seagull. The specimen found might not actually be an azcharchoid, but it certainly was from a pterosaur. Researchers were able to analyze the bones to determine whether or not it was juvenile or adult and found that the specimen was either fully grown or very close to being fully grown. For more on that, read the paper here.


Pterosaurs preserve terribly. They’re bones are hollow, their skeletons are fragile, they didn’t routinely die in nice, preserving environments. During the Cretaceous, pterosaurs shifted from marine to more non-marine habitats. This may account for the lack of data on small, difficult to preserve pterosaur fossils in the late Cretaceous. Terrestrial habitats do not preserve fragile fossils. Even much larger, denser bones do not often preserve well in terrestrial environments. The fossils that have been found from pterosaurs of this period are usually in very bad shape and are only fragments of the entire skeleton. Often times, fossils have to be looked at by many bird and pterosaur specialists before it can even be determined that the bone WAS from a pterosaur.  There is a lot of growing evidence suggesting that smaller pterosaurs in the late Cretaceous were not as rare as once believed.

Birds not the cause of pterosaur extinction

Pterosaurs were excellent fliers, almost definitely warm-blooded like birds (due to the energy expense of their lifestyle) and seemed able to adapt to a wide variety of niches. So it’s strange to imagine them going extinct due to their failure to diversify in the presence of birds. A study showed that pterosaurs actually diversified more after birds appeared. Pterosaurs had about a 160 million-year run on Earth and were relatively similar morphologically for the first 70 million years. They then began to experiment, trying out many modes of life. As birds became more successful, the pterosaurs actually responded by diversifying more. The emergence of birds (at least 50 million years after the first pterosaurs), encouraged the pterosaurs to try out new diets and feeding styles as seen by the rapid diversification of skull shapes in the fossil record. The general direction they went towards was much larger bodies. This was when the famous giant Quetzcoatlus types emerged.


  1. A small azhdarchoid pterosaur from the latest Cretaceous, the age of flying giants. Martin-Silverstone, Elizabeth, et al. Royal Society Open Science. 2016.
  2. Evolution of morphological disparity in pterosaurs. Katherine Prentice, Marcello Ruta, Michael Benton – Journal of Systematic Palaeontology – 2011




Hantavirus may pose bigger zoonotic threat than we thought

The adorable host of a virus that causes your lungs to fill with fluid.

A small, innocuous looking virus with just three genome segments, causes one of the most deadly infections in the United States. Hantaviruses circulate worldwide causing either hemorrhagic fever with renal syndrome (HFRS) or, in the case of the North and South American strains, Hantavirus pulmonary syndrome (HPS). Famously recognized in 1993 in the Four Corners region of the U.S., Sin Nombre Virus, a strain of hantavirus, still infects at least a few people in the U.S. every year.

Hantaviruses are thought of as a virus people only get directly from rodents, which cannot be transmitted person-to-person. Infections result from exposure to contaminated excretions/secretions of rodents infected with the virus, though the rodents themselves show no signs of disease. These rodents also transmit the virus to each other.

Coevolution with hosts

While many species may be drivers for the evolution of another, the term coevolution is applied when two species influence each other so much that they are evolving together, where one undergoes genetic change the other responds with genetic change. They are undergoing speciation together. It was thought for a while that rodents were unharmed by the virus due to long, ongoing rodent-hantavirus coevolution. Significant phylogenetic congruities have been shown, for example, the phylogeny shown:

Screen Shot 2017-09-07 at 9.36.14 PM
Host species phylogeny on left, virus phylogeny on right, lines indicate which host virus infects.

New research might be indicating that’s not as true as we thought, phylogenetic analysis studies may be flawed, host range my be bigger, and rodent speciation doesn’t match up. While I’m not enough of a hantavirus or rodent expert to weigh in on this, certainly “whoa if true” to the coevolution theory.

Person-Person Transmission

In 1996, an outbreak of hantavirus in Argentina occurred, yet there was especially low rodent density and there was strong evidence for person-person transmission.

Then in 2011, a similarly unusually outbreak in Chile occurred. An Andes hantavirus, a close relative to the North American Sin Nombre virus (meaning “no name” as the native Americans), was shown to be transmitted person-to-person. In an outbreak of 5 human cases, symptoms developed in 2 household contacts and 2 healthcare workers after exposure to the first patient patient. Analysis of isolates from each patient supported person-person transmission for the all secondary-case patients.

Hantavirus found in human saliva

You might optimistically tell yourself that maybe this Andes hantavirus was a unique case. And maybe hantavirus was still really just a rodent disease that rarely spilled over to a person. But in Sweden in 2008, a Puumala hantavirus that causes hemorrhagic fever with renal syndrome (nephropathia epidemica) was found in human saliva of 10 patients. Whether or not this is actually a mode of transmission or not remains to be seen, but it does seem like hantaviruses are becoming more adept at infecting and transmitting between human hosts.

Climate change’s effect on hantavirus?

Hantaviruses frequently jump hosts and seem to circulate amongst bats, moles, shrews, and rodents, but climate change and human impact generally decreases rodent diversity. Intuitively you may assume hantaviruses would be less able to jump hosts as global warming/human impact goes on.


Perhaps colder areas will actually see a decrease in hantavirus outbreaks as a result of global warming, due to the expected decrease in vole/northern rodent species populations. Yet that doesn’t seem to be what’s happening. Hantavirus surveillance has indicated an INCREASE, not only in outbreaks, but in genetic diversity and abundance in rodent populations.

If climate change does end up resulting in low rodent densities, this may also present another hantavirus risk– providing selective pressure for the virus to change transmittance route.

deer mouse dusted with fluorescent powder to identify which mice got in most fights/matings thereby spreading more hantavirus. It was big, old mice.


  1. University of Utah. “Big, Old Mice Spread Deadly Hantavirus.” ScienceDaily. ScienceDaily, 9 January 2009.

2. Phylogeny and Origins of Hantaviruses Harbored by Bats, Insectivores, and Rodents. Wen-Ping Guo-Xian-Dan Lin-Wen Wang-Jun-Hua Tian-Mei-Li Cong-Hai-Lin Zhang-Miao-Ruo Wang-Run-Hong Zhou-Jian-Bo Wang-Ming-Hui Li-Jianguo Xu-Edward Holmes-Yong-Zhen Zhang – PLoS Pathogens – 2013

3. An Unusual Hantavirus Outbreak in Southern Argentina: Person-to-Person Transmission? Rachel Wells – Emerging Infectious Diseases – 1997

4. Hantavirus RNA in Saliva from Patients with Hemorrhagic Fever with Renal Syndrome. Lisa Pettersson-Jonas Klingström-Jonas Hardestam-Åke Lundkvist-Clas Ahlm-Magnus Evander – Emerging Infectious Diseases – 2008

5. Person-to-Person Household and Nosocomial Transmission of Andes Hantavirus, Southern Chile, 2011. Constanza Martinez-Valdebenito-Mario Calvo-Cecilia Vial-Rita Mansilla-Claudia Marco-R. Palma-Pablo Vial-Francisca Valdivieso-Gregory Mertz-Marcela Ferrés – Emerging Infectious Diseases – 2014


Salty Antarctic Lake Provides Clue to Viral Evolution

In the Vestfold Hills region of Antarctica, a team of researchers have discovered a unique method of genetic exchange happening in a deep lake—so salty it remains unfrozen down to minus 20 degrees. In it, lives members of Haloarchaea, a class of Euryarchaeota that thrive in high salt conditions. These extremophiles are able to thrive by having extremely high rates of horizontal gene transfer, swapping genes with other genera even, to more rapidly evolve. Despite the shockingly high rate of gene sharing, the lake still maintains distinct species with no one dominant species winning out. The lake is incredibly cold, providing very little energy, so the archaea in this area only produce about six generations a year because they have to metabolize and reproduce so slowly.

While people have been aware of the archaeal extremophiles there for some time, it was only recently that anyone noticed their plasmids.

Haloarchaea colonies

The team discovered plasmids in one strain that were not behaving like regular plasmids. Plasmids are pieces of DNA independent of the host genome which replicate independently and are kept around usually only if they have some beneficial gene to the organism (e.g. antibiotic resistance). What differentiates a plasmid from a virus is the method of transmitting genetic information.

For background, a plasmid typically relies cell-cell contact or “conjugation”–when a sex pilus of a bacterial cell containing the plasmid will combine with another bacterium to transfer the plasmid, or is picked up as naked DNA. Other horizontal gene transfer methods would be transduction (genetic transfer via a virus) or transformation (the collecting of naked DNA from the environment).

Viruses travel, encased in a protein coat, and rely on lysing or budding off their host cell and finding new cells to attach to and enter (or, in the case of retroviruses and lysogens, integrating in the host DNA and being activated later in any of that host’s progeny).

But these plasmids are acting like viruses. The pR1SE (plasmid) encodes proteins that go into the host membrane and allow the membrane to bud into vesicles containing plasmid DNA. These vesicles could then infect more of the archaeal species, plasmid-less members. The plasmids could then replicate themselves in their new host cell.

Besides this just being cool because it’s a way we’ve never seen before of transmitting DNA (and because anything involving archaea in extreme environments is cool), it also may be representative of some early stage of viral evolution.

Viral evolution is a hugely debated topic with no one really agreeing on how viruses came about, whether they evolved many times or once then diversified, which came first in the evolution of life etc., but this does seem to support the idea that at least some groups of viruses may have started as plasmids.

Some people think the obvious answer to viral evolution is gene reduction (a lot of giant virus fans), others think it’s gene addition (what this supports). I think the answer is gradually proving to be both—that viruses have evolved independently many times throughout history, and you could probably find at least a few examples to best support each major theory.


  1. Susanne Erdmann, Bernhard Tschitschko, Ling Zhong, Mark J. Raftery, Ricardo Cavicchioli. A plasmid from an Antarctic haloarchaeon uses specialized membrane vesicles to disseminate and infect plasmid-free cells. Nature Microbiology, 2017

2. High level of intergenera gene exchange shapes the evolution of haloarchaea in an isolated Antarctic lake. Ricardo Cavicchioli et al. PNAS. 2013

Echinoderms’ deviation from the universal code


The very strangeness of Echinodermata is partly responsible for the dedication that specialists in the group feel. We revel in their weirdness.
-Rich Mooi

Given that every biology student in the world has been introduced to the standard genetic code, and likely uses it frequently, it is kind of baffling that so few of us ever bother to think much about it. As a longtime lover of systematics/molecular evolution, the knowledge that the “universal genetic code” is not actually universal has always caused me some level of concern when imagining how scientists cope with such an issue or if they even cope with the issue at all.

Usually when you look this up you find a lot of “the code is essentially universal, only a few exceptions have been found” which would imply that maybe one or two extremely obscure microorganisms violated this rule slightly. But mammals mitochondria actually contains four out of 64 codons that do not match the universal code. Echinoderms, yeast, platyhelminth worms, all follow slightly different mitochondrial DNA codes and protozoan and some bacteria even follow different nuclear DNA codes (nuclear being the only DNA bacteria have).

While there are 64 codons, there are fewer than 64 tRNAs, which use an anticodon sequence to recognize a codon on mRNA and carry the appropriate amino acid at the other end. Different tRNAs with the various amino acids will sort of float in and out until the right one’s bound. The third position of the anticodon (the ‘wobble position’) however, binds very loosely to the DNA which is why the tRNA usually relies on recognizing the first two nucleotides. Some amino acids can have multiple tRNAs recognizing them but RNA modifications in the anticodon region of tRNAs can result in the evolution of a deviation to the universal genetic code. The echinoderm’s genetic code evolution is particularly intriguing which is hardly surprising given everything else about them.

A recent Nature paper shows an example of how this works in echinoderms. In echinoderm mitochondrial DNA, the codon AAA, which according to the “universal code” should code for a lysine, actually codes for an asparagine. Analyzing the tRNALys isolated from a sea urchin, they discovered a modified hydroxylated nucleoside; hydroxyl-N6-threonylcarbamoyladenosine. This modified nucleoside adjacent to the anticodon prevents the mt-tRNALys from misreading AAA as lysine, allowing AAA to code for an asparagine.

Mitochondria generally use a codon-anticodon pairing rule that allows unmodified uridine at the anticodon first position to pair with all four nucleotides at the third codon position. When an amino acid only has two codons corresponding to it, the G forms a base-pair with pyrimidine, and modified uridines (5-carboxymethylaminomethyl-uridine being a commonly heard modification to the wobble position base) can discriminate purines from pyrimidines. The presence of a pseudouridine in starfish mt-tRNAAsn in the middle of the anticodon allows the tRNA to decode the AAA codon more efficiently than the unmodified tRNA. Also interesting, the mt-tRNAs possessing anticodons similar to tRNAAsn, but which only decode two codons each (tRNAHis, tRNAAsp and tRNATyr) all possess unmodified U (position 35), further indicating pseudouridine (Ψ35) is important for decoding the three codons.

While certainly not all examples of a modified genetic code work quite this way, it’s intriguing to realize how something generally portrayed as being set in stone, is relatively labile and dynamic.

Given that systematics has favored mitochondrial DNA for many phylogenetic analyses, this could have an effect on the results if using an amino acid alignment or a distance matrix where each amino acid change is weighted a certain amount. You could imagine an alignment between mammals, echinoderms, and reptiles for example, where an AAA to an AAG would be a synonymous mutation (as in, not changing the protein) in mammals and reptiles, but a nonsynonymous mutation (changing the amino acid) in echinoderms, thus deserving a different score. AGA and AGG which both code Arginine in the ‘universal’ code, code for a stop codon in our mtDNA, while our nuclear DNA’s stop codon (UGA), codes a tryptophan. An AUA isoleucine in our nuclear DNA is read as a methionine in our mtDNA. There are likely many more “exceptions to the rule” that we have no idea exist.


  1. Hydroxylation of a conserved tRNA modification establishes non-universal genetic code in echinoderm mitochondria. Asuteka NagaoMitsuhiro OharaKenjyo MiyauchiShin-ichi YokoboriAkihiko YamagishiKimitsuna Watanabe Tsutomu Suzuki. Nature Structural & Molecular Biology (2017).

2. Tomita, K.Ueda, T. & Watanabe, K. The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondriaNucleic Acids Res.2716831689 (1999).

Inducing cannibalism, “listening” for caterpillars- Plant defense


To protect themselves from hungry caterpillars, a tomato plant was shown to release chemicals that make it taste terrible to the caterpillars. The chemicals are so upsetting to the caterpillars that they decide to eat other caterpillars instead.

The research team who discovered this, sprayed the tomato plants with methyl jasmonate (which the plants produce in response to stress) to trigger defense mechanisms. The chemical acts as a signal, causing the plant to alter its chemistry, resulting in a plant that was much less appetizing to the caterpillars. The methyl jasmonate also can attract enemies of caterpillars like predators and parasitoids which will eat the herbivores.

So a tomato plant is being eaten by caterpillars and releases a chemical to warn the other plants and the other plants respond by releasing toxins that cause the caterpillars to become cannibalistic and eat each other instead of the plant. So the plants are communicating with one another and working together to alter the behavior of the caterpillar. The result is apparently larger stressed caterpillars nibbling on smaller caterpillars nearby causing some disgusting oozing.

What’s especially disturbing is the caterpillars seem to still revert to cannibalism even when other plant options are nearby. Why disperse farther when you could just eat a closer, unlucky smaller caterpillar I suppose.

Also congrats to that lucky undergrad who helped conduct this research and already got his name on a nature paper.

Listening for munching

Caterpillar chewing_free.jpg
Recording device next to munching caterpillar

In more amazing ways plants are able to ward off caterpillars, some plants seem to even respond to the vibrations of herbivory. the cabbage butterfly caterpillar munching the leaves an Arabidopsis plant results in the leaf moving up and down a miniscule amount. These vibrations were able to be recorded and played back to the plants so the scientists could compare plants left in silence to plants exposed to munching sounds (but no actual physical damage). The plants that were in the presence of the recording of chewing vibrations created an increased amount of mustard oil. Mustard oil is used as a defense against herbivores.

So just listening to the munching even with no caterpillars present somehow makes the plants better able to ward off future attacks.

The plants were exposed to other vibratory sounds none of which triggered any response. They have absolutely no idea how this works but it definitely provides more evidence that plants are amazingly adept to responding to all kinds of stimuli and information in the environment despite having no brains and being underestimated by basically everyone in science who is not a botanist.


  1. John Orrock, Brian Connolly, Anthony Kitchen. Induced defences in plants reduce herbivory by increasing cannibalism. Nature Ecology & Evolution, 2017
  2. Plants respond to leaf vibrations caused by insect herbivore chewing. M. Appel, R. B. Cocroft. July 2014