Creationism in Crisis - Evolution and Arms Races - How Resistance to Snake Venom Evolved in Caecilians

A caecilians. A legless amphibian

Yellow-striped caecilian, Ichthyophis kohtaoensis

How an unlikely amphibian survived its “Judgement Day” - Faculty of Science - University of Queensland


When one thinks of amphibians, it's usual to think in terms of frogs and toads, and newts and salamanders. However, there is a third group, the legless Caecilians, (pronounced Sicilians), which look superficially like earthworms.

Now a research team led by Associate Professor Bryan Fry of Queensland University, Australia, has shown how their evolution was strongly influence by group of venomous snakes, the elapids. These snakes evolved in what is now Australia when it was still part of the single landmass, Gondwana, around 50 to 60 million years ago (Late Paleocene to Early Eocene).

The distinct characteristic of the elapids is hollow fangs with which they inject powerful toxins into their victims.

The evidence of the resulting intense selection pressure and resulting evolutionary arms race as the snakes used their new ability to kill otherwise defenceless caecilians is a devastating refutation of several creationist articles of faith.

First, a brief background of the caecilian amphibians and the elapid snakes

Caecilians.

Caecilians are a fascinating group of amphibians that belong to the order Gymnophiona. They are often lesser-known compared to frogs and salamanders, but they exhibit unique characteristics and evolutionary adaptations that make them intriguing subjects of study.

1. Evolution and Fossil Record: Caecilians have a long evolutionary history, with fossil evidence dating back to the Mesozoic era, around 170 million years ago. Some of the earliest caecilian fossils have been found in Europe and North America. Over time, they have undergone various adaptations to suit their burrowing lifestyle.
2. Anatomy and Adaptations: Caecilians are characterized by their elongated, limbless bodies, and they bear a resemblance to earthworms or snakes. Their eyes are typically reduced in size, and some species have a unique tentacle-like structure on their head known as a "tentacle." The tentacle is thought to have sensory functions.
3. Behavior and Ecology: Most caecilians are fossorial, meaning they spend the majority of their lives underground, burrowing through soil and leaf litter. Their burrowing lifestyle has led to the reduction or complete loss of limbs. Caecilians are also known to be carnivorous, feeding on various invertebrates found in the soil.
4. Reproduction: Caecilians exhibit diverse reproductive strategies. Some species lay eggs, while others give birth to live young. Some species even practice parental care, with females protecting and nourishing the developing embryos.
5. Relationship with Other Amphibians: Caecilians, along with frogs and salamanders, belong to the class Amphibia. They are more closely related to salamanders than to frogs. Together, these three groups make up the extant amphibian diversity. The classification is as follows:
   • Class: Amphibia
     • Subclass: Lissamphibia
       • Order: Gymnophiona (Caecilians)
       • Order: Anura (Frogs)
       • Order: Caudata (Salamanders)

Further Reading:

1. Wilkinson, M., San Mauro, D., Sherratt, E., & Gower, D. J. (2011). A nine-family classification of caecilians (Amphibia: Gymnophiona). Zootaxa, 2874, 41-64. Link: https://www.biotaxa.org/Zootaxa/article/view/zootaxa.2874.1.3
2. San Mauro, D. (2010). A multilocus timescale for the origin of extant amphibians. Molecular Phylogenetics and Evolution, 56(2), 554-561. Link: https://www.sciencedirect.com/science/article/abs/pii/S1055790310001739

These references and further reading materials should provide you with a comprehensive understanding of caecilians, their evolutionary history, and their relationship with other amphibians. Happy exploring!

ChatGPT3 "What can you tell me about Caecilians - in particular when they evolved and how they relate to other amphibians. With references/further reading." [Response to user request]
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Elapid Snakes.

The elapid snakes are a diverse group of venomous snakes belonging to the family Elapidae. They include some of the most well-known venomous snakes, such as cobras, mambas, kraits, coral snakes, and sea snakes. The evolution of elapid snakes is a fascinating topic, and while I can provide a brief overview, please note that the field of evolutionary biology is continually evolving with new discoveries and insights.

1. Origin and Diversification: Elapid snakes are believed to have originated in the region that is now Australia and rapidly spread to various parts of the world. Molecular phylogenetic studies suggest that they diverged from other venomous snake lineages, such as the vipers, around 50 to 60 million years ago (Late Paleocene to Early Eocene). This early diversification likely occurred when Australia was still connected to Gondwana.
2. Adaptations and Venom: Elapid snakes are known for their highly potent venom, which they use for hunting and defense. Their venom contains a complex mixture of toxins that can immobilize or kill prey and deter potential predators. The evolution of venom in elapids is considered a crucial adaptation that allowed them to become highly successful predators.
3. Geographical Distribution: The dispersal of elapid snakes from Australia to other parts of the world is thought to have occurred through different mechanisms, including land bridges, island hopping, and rafting. For example, the migration of elapids from Australia to Southeast Asia likely occurred through land connections during periods of lowered sea levels.
4. Key Lineages: Elapids have diversified into various lineages, adapting to different environments and ecological niches. Some of the prominent lineages include the elapine snakes (e.g., cobras, kraits, and mambas), the hydrophiine snakes (sea snakes), and the coral snakes (genus Micrurus in the Americas).

References for further reading:

1. Lee, M. S. Y., Sanders, K. L., King, B., Palci, A., Daza, J. D., & Scanlon, J. D. (2016). Ancient dates or accelerated rates? Morphological clocks and the antiquity of placental mammals. Proceedings of the Royal Society B: Biological Sciences, 283(1823), 20161278. Link: https://royalsocietypublishing.org/doi/10.1098/rspb.2014.1278
2. Fry, B. G., Vidal, N., Norman, J. A., Vonk, F. J., Scheib, H., Ramjan, S. F. R., ... & Hodgson, W. C. (2006). Early evolution of the venom system in lizards and snakes. Nature, 439(7076), 584-588. Link: https://www.nature.com/articles/nature04328
3. Slowinski, J. B., & Keogh, J. S. (2000). Phylogenetic relationships of elapid snakes based on cytochrome b mtDNA sequences. Molecular Phylogenetics and Evolution, 15(1), 157-164. Link: https://www.sciencedirect.com/science/article/abs/pii/S105579039990725X
4. Scanlon, J. D., & Lee, M. S. (2000). The Pleistocene serpent Wonambi and the early evolution of snakes. Nature, 403(6768), 416-420. Link: https://www.nature.com/articles/35000188

These references should provide you with a more comprehensive understanding of the evolution and diversification of elapid snakes. You can access the full texts of these papers through academic institutions or by contacting the authors directly.

ChatGPT3 "Now tell me about the evolution of the elapid snakes. With some references, please." [Response to user request]
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What the Queensland University team found is that all the caecilians except those on the Seychelles islands were resistant to the venom of the elapid snakes. The conclusion is that the evolution of the elapid snakes produced an arms race and intense selection pressure on the caecilians to evolve immunity to the snake venom. Elapids have never reached the Seychelles, so there has been no pressure to evolve resistance.

Neurotoxic venom works by binding electrostatically onto receptors on the neurons of the victim. The caecilians evolved resistance to it in three stages, showing evidence of the intensity of the arms race.

1. Evolve barriers which prevent the toxins reaching the receptors.
2. When the snakes overcame 1, change the shape of the receptor so the toxin can't bind to it.
3. When that no longer works, make the receptor electrostatically charged, so it has the same charge as the toxin, and repels it to prevent it binding.

The research team have estimated that the caecilians have evolved resistance on at least 15 occasions.

As the Queensland University News release explains:

An international team of researchers has uncovered “unprecedented” snake venom resistance in an unexpected species – the legless amphibian known as caecilians.

Our research provides a textbook example of how a single predatory pressure can trigger an evolutionary cascade where the same way of fighting back arises independently multiple times in a species’ different lineages. In this case, the key predatory pressure was the rise of the elapid snakes, such as cobras and coral snakes, characterised by the evolution of a new way of delivering venom via their hollow, fixed, syringe-like fangs.

Despite being quite slippery, caecilians are worm-like in their locomotion and speed and were incredibly easy prey to cobras and other snakes, which used their fangs to kill them and eat them later. It would have been absolute carnage to the point where elapids were basically grazing on caecilians, contributing to the rapid spread of elapid snakes across Africa, Asia, and the Americas.

The caecilian’s ability to persevere and evolve despite these pressures is like a movie – like the survivors of Judgement Day fighting back by changing the chemical landscape.

Professor Bryan G. Fry, senior author.
Venom Evolutionary Lab
School of Biological Sciences
University of Queensland, St. Lucia, QLD, Australia

The University of Queensland’s Associate Professor Bryan Fry led the study, which he said provides a solid model for the fundamental evolutionary concept of predator-prey interactions.

The team studied caecilian species from across all known families across the globe, including species in the Seychelles islands never reached by elapid snakes.

Lead author, Marco Mancuso from Vrije Universiteit Brussel’s Amphibian Evolution Lab, said the study involved using tissue collections to sequence a part of the neuromuscular receptor in caecilians bound by toxins in snake venom.

We showed that resistance to elapid snake venom neurotoxins has evolved on at least 15 times – which is absolutely without precedent. A particularly interesting validation of the theory was that the caecilians on the Seychelles islands were not resistant to snake venom, which is consistent with elapid snakes never reaching those islands.

It’s an extraordinary signal for response to such severe selection pressure, where the survivors of the onslaught were those who were a bit less sensitive to the venom and some had mutations that made them completely immune. These were the ones that repopulated the earth after the elapid snake plague.

Dr. Marco Mancuso, lead author
Amphibian Evolution Lab
Biology Department
Vrije Universiteit Brussel, Brussels, Belgium

Dr Fry said the caecilians were able to achieve this never-before-seen venom resistance by deploying three different kinds of biological methods.

One kind [of resistance] is putting up a form of barricade that blocks the ability of the toxins to reach receptors that would normally elicit a deadly reaction.

A second form of resistance is changing the physical shape of the receptor. As the toxins have evolved to be like keys and insert into the lock-like receptor, changing the shape means the toxin no longer fits.

Lastly, caecilians essentially deploy an electromagnetic ‘weapon’ which reverses the charge during this toxin-receptor interaction. The positive-to-positive charge repulsion increases exponentially the closer the objects come together, like trying to force two magnets together. This pocket of the receptor is normally negatively charged, so snake toxins have evolved with a positive charge to help guide the binding. The mutation where the receptor is now positively charged like the toxins, electrostatically repels the toxins.

Animals killing other animals, and the prey evolving to escape the predators, is something that I think is always fascinating to people, especially young people just getting into science.

Professor Bryan G. Fry.

Dr Fry said while the results won’t lead to any new direct human benefits, such as new antivenom, the results have the benefit of showcasing an important evolutionary interaction in an engaging way to the next generation of scientists.

The research is published in the International Journal of Molecular Sciences.

Technical details are given in the abstract to the team's paper in the International Journal of Molecular Sciences:

Figure 1. Modifications to the post-synaptic nicotinic acetylcholine receptor (nAchR) conferring resistance to alpha-neurotoxins. (A) N-glycosylation at an NX(S/T) motif (at positions 187–189 or 189–191). This physical form of resistance creates spatial congestion, preventing larger molecules, such as alpha-neurotoxins, from reaching the binding site, while allowing smaller molecules, such as the neurotransmitter acetylcholine, to still reach their destination. (B) Substitution of proline residues at positions 194 or 197. This substitution creates a conformational change in the substrate and reduces toxin affinity to the receptor. (C) Introduction of a positively charged amino acid (arginine (R) or lysine (K)), which causes electrostatic repulsion of alpha-neurotoxins that are themselves also positively charged.

Mancuso M, Zaman S, Maddock ST, Kamei RG, et al.(2023)

Abstract

Predatory innovations impose reciprocal selection pressures upon prey. The evolution of snake venom alpha-neurotoxins has triggered the corresponding evolution of resistance in the post-synaptic nicotinic acetylcholine receptors of prey in a complex chemical arms race. All other things being equal, animals like caecilians (an Order of legless amphibians) are quite vulnerable to predation by fossorial elapid snakes and their powerful alpha-neurotoxic venoms; thus, they are under strong selective pressure. Here, we sequenced the nicotinic acetylcholine receptor alpha-1 subunit of 37 caecilian species, representing all currently known families of caecilians from across the Americas, Africa, and Asia, including species endemic to the Seychelles. Three types of resistance were identified: (1) steric hindrance from N-glycosylated asparagines; (2) secondary structural changes due to the replacement of proline by another amino acid; and (3) electrostatic charge repulsion of the positively charged neurotoxins, through the introduction of a positively charged amino acid into the toxin-binding site. We demonstrated that resistance to alpha-neurotoxins convergently evolved at least fifteen times across the caecilian tree (three times in Africa, seven times in the Americas, and five times in Asia). Additionally, as several species were shown to possess multiple resistance modifications acting synergistically, caecilians must have undergone at least 20 separate events involving the origin of toxin resistance. On the other hand, resistance in non-caecilian amphibians was found to be limited to five origins. Together, the mutations underlying resistance in caecilians constitute a robust signature of positive selection which strongly correlates with elapid presence through both space (sympatry with caecilian-eating elapids) and time (Cenozoic radiation of elapids). Our study demonstrates the extent of convergent evolution that can be expected when a single widespread predatory adaptation triggers parallel evolutionary arms races at a global scale.

Mancuso M, Zaman S, Maddock ST, Kamei RG, Salazar-Valenzuela D, Wilkinson M, Roelants K, Fry BG.
Resistance Is Not Futile: Widespread Convergent Evolution of Resistance to Alpha-Neurotoxic Snake Venoms in Caecilians (Amphibia: Gymnophiona).
International Journal of Molecular Sciences. 2023; 24(14):11353. https://doi.org/10.3390/ijms241411353

Copyright: © 2023 The authors.
Published by MDPI, Basel, Switzerland. Open access
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

What we have in this piece of research is confirmation of the fact that the Theory of Evolution by Natural Selection continues to be the basis for understanding the observed facts. Certainly, the research team who conducted this research had no doubt that the present immunity to snake venom that the caecilians have is the result of an evolutionary arms race between the venomous snakes and the caecilians.

The absence of this resistance in the caecilians of the Seychelles from which the elapid snakes are absent is a sort of control confirming that it is the presence of venomous predators that was the environmental driver of the evolution of resistance.

It's hardly worth pointing out that arms races themselves are utterly inconsistent with the notion of intelligent [sic] design because no intelligent designer would indulge in an arms race with itself, acting as though the solution it designed for one problem is now a problem awaiting a solution, which will become a new problem to be solved...

And maybe a creationist will have the courage to explain how the mutations that gave these levels of resistance to snake venom can be regarded as 'devolutionary', as Michael J Behe would have his dupes believe, or how this evidence of beneficial mutations is consistent with the creationist dogma that all mutations are deleterious and therefore can't contribute to evolution.

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