The tale of Toxicofera, part 1 (which animals are venomous? part 2)

Nature is messy and defies our attempts to "carve it at the joints". Which animals are "venomous"?  It still depends on whom you ask. Tune in for part 1 of the tale of Toxicofera!

Academics are always arguing. Maybe that sounds to you like an unfortunate consequence of too many egos or too little funding, but it’s actually the way science and all other philosophical disciplines make progress. You see, the growth of knowledge is an evolutionary process. Ideas are put forward in the form of conjectures or hypotheses and these are criticised by further arguments or experiment – controlled experiments are the form of criticism that distinguishes science from other disciplines that seek to uncover knowledge. As many epistemologists (people who study the processes that help us to acquire knowledge) have noted, this is analogous to the way in which organisms are tested (criticised?) by their environments. The “fittest” organisms are like the best arguments – they’re the ones that can survive the most criticism and go on to have lots of babies (in the case of organisms) or become fully fledged theories (in the case of hypotheses). So, arguments are always flying back and forth amongst scientists and this constant debating is actually a very good thing – without it, we really couldn’t work out which ideas are the best. Often, people imagine that “consensus” – everyone agreeing – is the goal within a scientific field, but based on the above it’s easy to see why this is not the case. Consensus is not necessarily a sign of a healthy field of scientific enquiry, rather it’s characteristic of a field in which there are no new ideas and therefore no progress.

This painting by Jan Steen - "Argument over a card game" - reminds me of one of two toxinology conferences I've attended.

As we discussed last week, something toxinologists continue to debate is which animals are rightly considered “venomous”. For some, any animal actively delivering toxins to another in order to get a meal or defend itself should be classified venomous, whereas others have maintained that predatory venoms are secretions used to subdue or even kill potential prey animals. Injected secretions that facilitate feeding for parasites like mosquitoes or leeches are therefore a point of contention between these two perspectives. The classification of many reptile species is perhaps even more contentious. The primary reason for this is the diversity in the development of (potential) “venom delivery” systems amongst members of a group of reptiles called “Toxicofera”. On top of that, the name and membership of the group are more than enough to make some herpetologists (people who study reptiles and amphibians) uncomfortable, even before we start debating which ones are “truly venomous”. “Fera'' means “having” or “bearing” and “toxico” is fairly self-explanatory – according to its name, Toxicofera is that group of reptiles which “bears toxins”.

To understand why this is controversial, we first have to look at the membership of the group – which reptiles are toxicoferan? Systematics is the classification department of biology – systematists are biologists who study the relationships amongst organisms and gather them into clades, which are groups descended from a common ancestor. If they’ve done their job well, all members of a clade are more closely related to each other than they are to members of any other clade. Clades are hierarchical, so Reptilia is the clade which contains all reptiles and is ranked as a class. Traditionally, the next rank is order – Squamata is the order that contains all lizards (including snakes). Next comes family – Elapidae is the family that all of Australia’s front-fanged venomous snakes belong to. Next is genus (plural: genera) – Pseudonaja is the genus that brown snakes belong to – and finally species. The system used to be nice and neat, with a fixed number of ranks, but the more we study nature the more complex we realise it is. As a result, there are now many ranks that intervene between those in the traditional hierarchy and are qualified with prefixes such as “sub-” (e.g. suborder) and “super-” (e.g. superfamily). Each species has a “binomial name” – Pseudonaja textilis is the eastern brown snake – which for arcane reasons is always italicised, with the generic name capitalised and the species name given in lower case. Each of these groups is a clade – all members of Pseudonaja, for example, are (according to our current understanding) more closely related to each other than they are to say, Pseudechis, which is the genus that the “black snakes” belong to. As Andrew pointed out last week, we’re not particularly imaginative with our common names, which is part of what makes the binomial scientific name so important.

Cladograms are diagrams which depict evolutionary relationships. At the end of each branch is a clade, a group of species which are more closely related to each other than they are to species on other branches. Wikimedia Commons. 

Toxicofera is a clade which ranks in between order (it’s part of the order Squamata) and suborder (I know, the old system seems to be breaking down at this point). It contains two suborders and an infraorder (argh! Please make it stop!)….and this is where the controversy begins (not, as you might imagine, with all those messy subdivisions of the classificatory hierarchy). The 3 groups that belong to Toxicofera are the iguanas and their relatives (Iguania), the goannas and their relatives (Anguimorpha) and the snakes (Serpentes). Again, you might think the controversy would stem from the claim that snakes are more closely related to goannas than goannas are to geckos, but actually it has long been understood that snakes are a highly successful group of legless lizards and even that goannas and other anguimorph lizards (including the famously venomous gila monster and Mexican beaded lizard) might be their closest relatives. The controversy begins with Iguania – the clade that contains the dragon lizards (like Australia’s bearded dragons and frilled lizards), along with iguanas and chameleons. For a long time, systematists used morphology – the size, shape and arrangement of anatomical features – to determine which animals were closely related. Based on these sorts of measurements, Iguania is the first group to break away from the rest of the lizards – under this scheme, geckos are closer to goannas (and snakes) than either of them is to iguanas. This all changed when gene sequencing became a popular way of determining relationships. When studies based on similarities between genes (instead of anatomical features) investigated the relationships among lizards, it turned out that Iguania wasn’t as divergent as previously thought, and Toxicofera was born.

This eastern bearded dragon (Pogona barbata)  is a member of the family Agamidae and the suborder Iguania. Iguanian lizards are one of the three clades that compose the Toxicofera. This grouping of Iguania with Serpentes and Anguimorpha (see below) was considered controversial because Iguania was considered the "outgroup" to all other Squamata (snakes and lizards). This split was made partly due to the fact that iguanian lizards like the bearded dragon (and, more famously, chameleons) use their tongues to capture prey, whereas other lizards (including snakes) primarily use their tongues for chemoreception. Despite being a member of the "toxin bearing" clade (Toxicofera), bearded dragons are non-venomous (but they can certainly bite!). Photo: Timothy Jackson.

There are still some holdouts who argue that we don’t really understand how to estimate relationships based on gene sequences, but the molecular systematists retort that we have never known how to estimate relationships based on morphology (and remember, this kind of disagreement isn’t necessarily a bad thing). Never you mind, insist the gene jockeys (thumbing their noses at the old-fashioned anatomists), that iguanian lizards use their tongues to catch their prey and other lizards use their tongues to detect their prey – the genes don’t lie! Whichever group turns out to be right in the long run, it’s fair to say that molecular systematics is now the dominant method used to classify organisms. As a result, most herpetologists now accept that Toxicofera is indeed a legitimate clade…..even if they still don’t like the name. Happily, there’s still plenty to argue about when it comes to toxic reptiles!

This lace monitor (Varanus varius) is a member of the family Varanidae and the infraorder Anguimorpha. Anguimorpha is one of the three clades that compose the Toxicofera. It remains highly controversial whether or not monitor lizards (which are also known as "goannas") should be properly considered "venomous" - be sure to read the next instalment in this series to find out why. Photo: Timothy Jackson.

It’s clear that Toxicofera contains all the extant (the opposite of extinct) venomous reptiles, but this is very different from saying that all members of the clade are venomous. It seems pretty obvious to most of us that bearded dragons aren’t venomous, but for many toxicoferan reptiles it’s not so clear cut. This is because the anatomy that is responsible for producing and delivering toxic secretions is extremely variable within the clade. In this way, Toxicofera differs from a lot of other clades of venomous organisms in which all members have relatively similar venom production and delivery systems. One reason for this is that a lot of other venomous clades are far more ancient than Toxicofera and their venom systems have stayed pretty much the same for hundreds of millions of years. 400 million year old fossilised centipede venom claws, for example, are very similar to the venom claws of the centipedes which live under your bed right now….just kidding, they’re usually out in the garden, but I think we can all agree that centipedes are the stuff of nightmares!

This female giant centipede (Ethmostigmus rubripes) is guarding eggs she produced parthenogenetically - without any input from a male. Maybe centipedes can do this because even they are too afraid of each other to get close enough to do it the old-fashioned way? To be fair, centipedes do reproduce sexually as well….they just might need a few stiff drinks to get their nerve up! Photo: Timothy Jackson. 

Amongst snakes, there are a few groups that have hollow fangs at the front of their mouths which are connected by enclosed ducts to a venom gland that is associated with compressor musculature. This “high-pressure” venom delivery system works like a hypodermic needle – the muscles squeeze the gland, propelling venom through the duct and out the tip of the hollow fang. It’s a quintessential venom delivery system and many venomous clades, from bees and wasps to spiders, scorpions to centipedes, have something similar. The thing is, these groups of front-fanged venomous snakes are not all descended from a single front-fanged ancestor. In fact, their highly specialised anatomy evolved separately – a beautiful example of “convergent evolution”, in which multiple groups of organisms independently evolve similar structures associated with the same functional role. Many other snakes have grooved (not hollow) fangs at the back of their mouths, also associated with a toxin-secreting gland, but in most such cases the gland has no muscular tissue attached to it. These snakes have “low-pressure” venom delivery systems, which are generally considered to be less efficient than those of the front-fanged species. Other snakes have enlarged teeth without grooves, and some don’t have any special teeth for delivering venom at all, but may still have a toxin-secreting gland that is recognisable as a “venom gland”. There isn’t a simple relationship between how specialised the anatomy of a venom system is and how toxic the snake’s venom is, either – some species without grooved fangs have killed people, whereas many front-fanged species are not really dangerous to us at all.

The impressive fangs of this boomslang (Dispholidus typus) are located halfway along its top jaw - the boomslang is a classic "in-betweener". Its fangs are semi-hollow and its venom gland has a small amount of compressor musculature attached to it. Note that this individual has two fangs on either side, a common arrangement for boomslangs. These African tree snakes have a very potent venom that attacks the blood and have been responsible for a number of fatal bites to humans. Photo: Timothy Jackson.

When we consider Toxicofera as a whole, the situation becomes even more complicated. All members of the group seem to have “dental glands”, which are exactly what they sound like – glands associated with the teeth. Dental glands likely have a number of functions (including dental hygiene!), but they intuitively make sense as precursors to venom glands which secrete toxins that are delivered by specialised teeth. Amongst the Toxicofera, dental glands and associated teeth exist in every single arrangement imaginable (assuming you have a very good imagination!). It’s often claimed by those who wish to discredit evolutionary biology that we lack the links that would connect one species to another. These so-called “missing links” are transitional forms – if evolution is a gradual change of one type of organism into another type of organism, why don’t we ever see an “in-betweener” (hopefully I’m not violating any copyright here)? The answer is that we do see transitional forms, constantly. Transitional forms are what the entire field of systematics (whether molecular or morphological) is based upon – how could we tell which organisms are more closely related to others except by noting that some are very similar to each other and some far less so? The myriad arrangements of dental glands and dentition in Toxicofera underline this point (as do the proliferations of sub- and -infra- and super- clades) – we have far more transitional forms than we can possibly classify. In fact, when you look closely enough, nature is just one big smear of transitional forms that defies our desperate desire to classify things into clearly definable categories. Words are digital, nature is analogue.

One response to all this might be to say that we should do away with classificatory systems altogether, since they are so woefully inadequate to the task. This would be extreme! Instead of throwing the baby out with the bathwater, we need only remind ourselves that classifications (and indeed words in general) are like maps – even though maps don’t contain every detail of the territory they describe, we still find them indispensable for finding our way around. So, how can an appreciation of the continuous variability of nature help us to decide which animals are venomous? Thankfully, although we will have to admit that there is no bright line between “venomous” and “non-venomous”, there are a number of conceptual tools we can use to help us consider this issue. These include the idea of a “function category” – a grouping of organismal traits (such as anatomical features, or behaviours) according to their purpose. “Venom glands”, for example, is the name of a function category that includes all secretory tissue that is aggregated into a gland specialised for the production of venom. The venom glands of bees, snakes, stonefish, and myriad other organisms are grouped together in this category. A structure can be a member of multiple function categories – many anatomical features, including venom glands, may have multiple functions. For example, in addition to secreting toxins for subduing prey, a venom gland may also secrete enzymes that are useful for digestion. Another important piece of the puzzle is the distinction between “marginal” and “paradigmatic” members of these function categories. Paradigmatic venom glands are those that have multiple features indicative of their specialisation for the purpose of producing and delivering venom (more details of these next time). Marginal venom glands also produce venom, but may be far less specialised for doing so. All this can get a bit confusing – remember, nature is complex but its boundless beauty is a consequence of that complexity. We’re going to have a more in-depth look at these concepts, and hopefully demystify them, in the next exciting instalment of “the tale of Toxicofera”.

The Papuan taipan (Oxyuranus scutellatus) possesses a paradigmatic venom system, with a hollow fang at the front of the top jaw and a large venom gland, which can be clearly seen in this dissection of a road-killed specimen. Photo: Tom Charlton.

Finally, we must always bear in mind that the question of whether or not an organism is venomous is ultimately a question about that organism’s ecology. Venom is, by definition, a trait that one organism uses on another – ecology is the study of relationships among organisms and therefore venom is intrinsically ecological. This can make it really hard, but also incredibly fascinating, to study. In order to decide whether or not a particular secretion is indeed a “venom”, we need to know how the organism that produces it uses it. Remember the example from last week comparing the taipan and the tree snake. If we watch a snake bite and then release a mouse, see the mouse take a few steps before falling down dead, and then see the snake consume the mouse, it’s easy to say – “aha, that snake is venomous!”. If all we can see is a snake grappling with a lizard, biting it repeatedly and wrapping coils around it, struggling for several minutes until finally overcoming the lizard and managing to swallow it…..it’s a little bit harder to work out if venom was involved or not. We may need to take into account additional sources of evidence – what do the snake’s teeth and dental glands look like? What activities does the secretion of the dental gland have when we test it in the lab? What genes does the dental gland express?

And so the scientific quest to understand the natural world continues – studying nature is not always about arriving, once and for all, at definitive answers; sometimes it’s just about peeling back one layer only to find another….and another….and another. Sometimes it’s about seeing how deep the rabbit hole goes.

Phew! If you’ve made it this far – well done! Thank you for reading and please check back for the next episode.