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Toxins
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Venom Genes and Genomes of Venomous Animals: Evolution and Variation
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Venom Genes and Genomes of Venomous Animals: Evolution and Variation

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (28 July 2025) | Viewed by 16438

Special Issue Editors

Dr. Nancy Oguiura

E-Mail Website
Guest Editor
Ecology and Evolution Laboratory, Instituto Butantan, Sao Paulo 05503-900, SP, Brazil
Interests: snake beta-defensins; snake venom and toxins; molecular evolution; gene expression
Dr. Maria José J. Silva

E-Mail Website
Guest Editor
Ecology and Evolution Laboratory, Instituto Butantan, Sao Paulo 05503-900, SP, Brazil
Interests: cytogenetics; molecular phylogeny; phylogeography; biodiversity conservation and evolution

Special Issue Information

Dear Colleagues,

The evolution of a gene occurs not only after point mutations, insertions, or the deletions of sequences but also due to its location in the genome, which may encompass recombinations, duplications, and/or other events. In this way, it is interesting to study not only the toxin genes but also the genome of venomous animals in all forms of organization, which includes chromosomes and chromosome evolution. In addition, the localization of toxin genes in the chromosome can influence the expression of that toxin.

Thus, this Special Issue aims to publish what has been done to toxins at the genetic level, as well as studies related to the genomes and chromosomes of venomous animals from evolutionary and multidisciplinary perspectives, thus looking at the evolution of toxins and venoms in an interdisciplinary way.

Reviews and research papers on genetic and biochemical aspects of venom polymorphism, toxin variation, toxin expression, and genomes of venomous animals are accepted, as well as explorations of co-evolution from an interdisciplinary approach.

Dr. Nancy Oguiura
Dr. Maria José J. Silva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • venom polymorphism
  • toxin evolution
  • gene expression
  • gene structure
  • genome evolution
  • gene family
  • transcriptome
  • genome structure and organization
  • next-generation sequencing
  • co-evolution
  • convergent evolution

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Published Papers (4 papers)

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Research

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19 pages, 2845 KB  
Article
Neurotoxic Sleight of Fang: Differential Antivenom Efficacy Against Mamba (Dendroaspis spp.) Venom Spastic-Paralysis Presynaptic/Synaptic vs. Flaccid-Paralysis Postsynaptic Effects
by Lee Jones, Mimi Lay, Lorenzo Seneci, Wayne C. Hodgson, Ivan Koludarov, Tobias Senoner, Raul Soria and Bryan G. Fry
Toxins 2025, 17(10), 481; https://doi.org/10.3390/toxins17100481 - 26 Sep 2025
Viewed by 8311
Abstract
Mamba (Dendroaspis species) snakebites are critical medical emergencies across sub-Saharan Africa. Envenomings can result in the rapid onset of complex neurotoxic symptoms, often leading to high rates of mortality without timely intervention with antivenom. The ancestral state of mambas is the green [...] Read more.
Mamba (Dendroaspis species) snakebites are critical medical emergencies across sub-Saharan Africa. Envenomings can result in the rapid onset of complex neurotoxic symptoms, often leading to high rates of mortality without timely intervention with antivenom. The ancestral state of mambas is the green coloured, forest dwelling type, with the tan/grey coloured, savannah dwelling D. polylepis (Black Mamba) representing a derived state both ecologically and morphologically. However, it has not been tested whether these changes are paralleled by changes in venom biochemistry or if there are differential molecular evolutionary patterns. To fill these knowledge gaps, this study evaluated the neurotoxic effects of all Dendroaspis species venoms using the chick biventer cervicis nerve-muscle preparation, assessed the neutralizing efficacy of three antivenoms commercially available in Africa, and reconstructed the molecular evolutionary history of the toxin types to ascertain whether some were unique to particular species. All Dendroaspis venoms demonstrated potent flaccid-paralysis due to postsynaptic neurotoxicity. The only exception was D. angusticeps venom, which conversely exhibited spastic-paralysis due to presynaptic/synaptic neurotoxicity characterised by potentiation of acetylcholine presynaptic release and sustained synaptic activity of this neurotransmitter. Antivenom efficacy varied significantly. All three antivenoms neutralized to some degree the flaccid-paralysis postsynaptic effects for all species, with D. viridis venom being the best neutralized, and this pattern extended to all the antivenoms. However, neutralisation of flaccid-paralysis postsynaptic effects unmasked spastic-paralysis presynaptic/synaptic neurotoxicity within non-angusticeps venoms. Spastic-paralysis presynaptic effects were poorly neutralized for all species by all antivenoms, consistent with prior clinical reports of poor neutralisation of spastic-paralytic effects. Geographic variation in D. polylepis venom was evident for the relative neutralisation of both spastic-paralysis presynaptic/synaptic and flaccid-paralysis postsynaptic/synaptic neurotoxic pathophysiological effects, with differential neutralization capabilities noted between the Kenyan and South African populations studied. Molecular phylogenetic analyses confirmed spastic-paralysis and flaccid- paralysis toxins to be a trait that emerged in the Dendroaspis last common ancestor, with all species sharing all toxin types. Therefore, differences in venoms’ pathophysiological actions between species are due to differential expression of toxin isoforms rather than the evolution of species-specific novel toxins. Our findings highlight the synergistic nature of flaccid-paralysis postsynaptic and spastic-paralysis presynaptic/synaptic toxins, while contributing significant clinical and evolutionary knowledge of Dendroaspis venoms. These data are crucial for the continued development of more effective therapeutic interventions to improve clinical outcomes and for evidence-based design of clinical management strategies for the envenomed patient. Full article
(This article belongs to the Special Issue Venom Genes and Genomes of Venomous Animals: Evolution and Variation)
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14 pages, 1611 KB  
Article
Explaining Echis: Proteotranscriptomic Profiling of Echis carinatus carinatus Venom
by Salil Javed, Prasad Gopalkrishna Gond, Arpan Samanta, Ajinkya Unawane, Muralidhar Nayak Mudavath, Anurag Jaglan and Kartik Sunagar
Toxins 2025, 17(7), 353; https://doi.org/10.3390/toxins17070353 - 16 Jul 2025
Cited by 1 | Viewed by 2508
Abstract
Snakebite remains the most neglected tropical disease globally, with India experiencing the highest rates of mortality and morbidity. While most envenomation cases in India are attributed to the ‘big four’ snakes, research has predominantly focused on Russell’s viper (Daboia russelii), [...] Read more.
Snakebite remains the most neglected tropical disease globally, with India experiencing the highest rates of mortality and morbidity. While most envenomation cases in India are attributed to the ‘big four’ snakes, research has predominantly focused on Russell’s viper (Daboia russelii), spectacled cobra (Naja naja), and common krait (Bungarus caeruleus), leading to a considerable gap in our understanding of saw-scaled viper (Echis carinatus carinatus) venoms. For instance, the venom gland transcriptome and inter- and intra-population venom variation in E. c. carinatus have largely remained uninvestigated. A single study to date has assessed the effectiveness of commercial antivenoms against this species under in vivo conditions. To address these crucial knowledge gaps, we conducted a detailed investigation of E. c. carinatus venom and reported the first venom gland transcriptome. A proteotranscriptomic evaluation revealed snake venom metalloproteinases, C-type lectins, L-amino acid oxidases, phospholipase A2s, and snake venom serine proteases as the major toxins. Moreover, we assessed the intra-population venom variation in this species using an array of biochemical analyses. Finally, we determined the venom toxicity and the neutralising efficacy of a commercial antivenom using a murine model of snake envenoming. Our results provide a thorough molecular and functional profile of E. c. carinatus venom. Full article
(This article belongs to the Special Issue Venom Genes and Genomes of Venomous Animals: Evolution and Variation)
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16 pages, 2115 KB  
Article
Evolution of Three-Finger Toxin Genes in Neotropical Colubrine Snakes (Colubridae)
by Kristy Srodawa, Peter A. Cerda, Alison R. Davis Rabosky and Jenna M. Crowe-Riddell
Toxins 2023, 15(9), 523; https://doi.org/10.3390/toxins15090523 - 25 Aug 2023
Cited by 5 | Viewed by 3210
Abstract
Snake venom research has historically focused on front-fanged species (Viperidae and Elapidae), limiting our knowledge of venom evolution in rear-fanged snakes across their ecologically diverse phylogeny. Three-finger toxins (3FTxs) are a known neurotoxic component in the venoms of some rear-fanged snakes (Colubridae: Colubrinae), [...] Read more.
Snake venom research has historically focused on front-fanged species (Viperidae and Elapidae), limiting our knowledge of venom evolution in rear-fanged snakes across their ecologically diverse phylogeny. Three-finger toxins (3FTxs) are a known neurotoxic component in the venoms of some rear-fanged snakes (Colubridae: Colubrinae), but it is unclear how prevalent 3FTxs are both in expression within venom glands and more broadly among colubrine species. Here, we used a transcriptomic approach to characterize the venom expression profiles of four species of colubrine snakes from the Neotropics that were dominated by 3FTx expression (in the genera Chironius, Oxybelis, Rhinobothryum, and Spilotes). By reconstructing the gene trees of 3FTxs, we found evidence of putative novel heterodimers in the sequences of Chironius multiventris and Oxybelis aeneus, revealing an instance of parallel evolution of this structural change in 3FTxs among rear-fanged colubrine snakes. We also found positive selection at sites within structural loops or “fingers” of 3FTxs, indicating these areas may be key binding sites that interact with prey target molecules. Overall, our results highlight the importance of exploring the venoms of understudied species in reconstructing the full evolutionary history of toxins across the tree of life. Full article
(This article belongs to the Special Issue Venom Genes and Genomes of Venomous Animals: Evolution and Variation)
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Review

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51 pages, 17514 KB  
Review
Variations in “Functional Site” Residues and Classification of Three-Finger Neurotoxins in Snake Venoms
by R. Manjunatha Kini and Cho Yeow Koh
Toxins 2025, 17(8), 364; https://doi.org/10.3390/toxins17080364 - 24 Jul 2025
Cited by 1 | Viewed by 1449
Abstract
Three-finger toxins (3FTxs) are the largest group of nonenzymatic toxins found in snake venoms. Among them, neurotoxins that target nicotinic acetylcholine receptors are the most well-studied ligands. In addition to the classical neurotoxins, several other new classes have been characterized for their structure, [...] Read more.
Three-finger toxins (3FTxs) are the largest group of nonenzymatic toxins found in snake venoms. Among them, neurotoxins that target nicotinic acetylcholine receptors are the most well-studied ligands. In addition to the classical neurotoxins, several other new classes have been characterized for their structure, receptor subtype, and species selectivity. Here, we systematically analyzed over 700 amino acid sequences of three-finger neurotoxins that interact with nicotinic acetylcholine receptors. Based on the amino acid residue substitutions in the functional sites and structural features of various classes of neurotoxins, we have classified them into over 150 distinct subgroups. Currently, only a small number of typical examples representing these subgroups have been studied for their structure, function, and subtype selectivity. The functional site residues responsible for their interaction with specific receptor subtypes of several toxins are yet to be identified. The molecular details of each subgroup representative toxin with its target receptor will contribute towards the understanding of subtype- and/or interface-selectivity. Thus, this review will provide new impetus in the toxin research and pave the way for the design of potent, selective ligands for nicotinic acetylcholine receptors. Full article
(This article belongs to the Special Issue Venom Genes and Genomes of Venomous Animals: Evolution and Variation)
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