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1 May 2026

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Transcriptomic and Proteomic Study on Animal Venom: Looking Forward

Instituto Butantan/Fundação Butantan, São Paulo 05503-900, SP, Brazil
Toxins2026, 18(5), 213;https://doi.org/10.3390/toxins18050213
This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward
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Transcriptomic and proteomic studies concerning venom and venom glands have provided major breakthroughs in the characterization and knowledge of global crude venom compositions and have also allowed for the identification of new toxins and activities. Venom gland transcriptomes (mRNA) and proteomes (proteins) share a high degree of concordance regarding the major toxins produced, meaning the most heavily transcribed genes in the gland generally correspond to the most abundant proteins in the venom. These approaches are based heavily on specific techniques that allow for in-depth characterization and knowledge of global crude venom compositions like DNA sequencing and mass spectrometry, respectively. However, the transcriptome–proteome relationship is not perfectly linear, with studies often showing that venom gland transcriptomes contain a larger, more diverse array of “potential” toxin transcripts, while the proteome reflects only the “actual” translated products identified [1,2,3,4,5,6,7,8,9].
Commonalities between the venom gland transcriptome and proteome include:
  • Dominant Toxin Representation: In both profiles, venom composition is dominated by a few major toxin superfamilies, such as phospholipases (PLA2s), metalloproteinases (SVMPs), and three-finger toxins (3FTxs), depending on the species analyzed.
  • High Expression and Production Levels: The mRNA levels (transcriptome) in the gland generally correlate with the protein abundance (proteome) in the raw venom, indicating that transcription directly dictates the high volume of toxin production. Major transcripts correlate with the major toxins expressed.
  • Structural Similarities and Fold Types: Both approaches commonly identify the same characteristic cysteine-rich toxins, though both approaches do not provide direct tertiary or quaternary structures.
  • Multifamily Organization: Both profiles reveal that toxins are organized into similar families and subfamilies, often with high levels of sequence similarity between them, and a significant fraction of toxins are structurally organized and combined with defined domains. Many toxin families have evolved by a process of gene duplication, with non-toxin paralogs typically being coexpressed in non-venom-gland tissues at low levels.
  • Identification of Secretory Machinery: While the transcriptome identifies the toxin mRNA, it also reveals high expression of genes related to protein folding (e.g., protein disulfide isomerases) and processing, which are then detected as functional enzymes (e.g., chaperones) in the proteome.
  • Venom plasticity: Venom composition is not static; it can shift during development (e.g., between newborn and adult snakes) or based on diet, suggesting a highly dynamic evolutionary response to environmental pressure.
These advances in general knowledge were only possible thanks to the integration of proteomic and transcriptomic approaches [10,11,12,13,14,15]. Genomic data is also important and complements the understanding of toxin evolutions [16,17].
However, major distinctions have also been observed:
  • Discrepancy in Abundance: The transcriptome often shows high diversity with many rare transcripts, whereas the proteome is focused on the most active, highly expressed products.
  • Post-Translational Modifications (PTMs): The proteome reveals modifications like C-terminal amidation and protein glycosylation that are predicted by the transcriptome but only confirmed as functional products in the venom itself.
  • Isoform Variation: Transcriptomics may predict numerous protein isoforms (variants) due to alternative splicing, but only a fraction may be translated and detected in the venom proteome.
Altogether, these approaches are complementary in order to provide a more complete understanding of the structure, function and evolution of toxins in venom composition [14,15,16,17,18,19,20,21].
The knowledge provided by these studies may potentially lead to drug discovery and new therapeutics besides the major ones already in the market for:
  • Pain Management: Identification of conotoxins from cone snails has led to drugs like Ziconotide.
  • Cardiovascular and Metabolic Disorder Treatments: Identification of bradykinin and bradykinin-potentiating peptides in snake venom contributed to the development of ACE inhibitors (e.g., Captopril) and the study of new metabolic disorder (and aesthetic) treatments like Ozempic.
Rather than identifying single toxins, these omics studies offer a complete “snapshot” of the molecular arsenal of venomous organisms. In light of this, the published articles and reviews in this Special Issue, “Transcriptomic and Proteomic Studies on Animal Venom: Looking Forward”, provide new data and discussions generated by these technical approaches, contributing new findings on and extending the current knowledge to more venomous species, the complexity of venom mixtures, clinical, biochemical and toxic aspects, cellular responses induced by specific toxins, structural characterization of low-abundance venom transcripts, the role of extracellular vesicles in envenomation and pathophysiology, potential new achievements, and many other aspects. We hope that this Special Issue will contribute by shedding some light on the bright future of this important field of science.

Conflicts of Interest

The author declares no conflict of interest.

List of Contributions

  • Sozanski, K.S.; Coelho, G.R.; Ishihara, M.A.; Delgado, A.; Adams, R.M.M. Megalomyrmex milenae Transcriptome Reveals a Complex Venom Cocktail. Toxins 2026, 18, 55. https://doi.org/10.3390/toxins18010055.
  • Lima, L.C.; Covali-Pontes, H.R.; Leite, O.G.S.; Perdomo, R.T.; Moraes, L.F.R.N.; Migliolo, L.; Moyses, M.N.; Santos, N.G.P.D.; Pimenta, D.C.; Rodrigues, M.S.; et al. Analysis of the Proteome and Biochemistry of Venom from Tityus confluens, a Scorpion That Can Be Involved in Severe Envenomation Cases in Brazil. Toxins 2025, 17, 406. https://doi.org/10.3390/toxins17080406.
  • Falla, M.V.; Sousa, E.P.; Morais-Zani, K.; Valladão, R.; Santos, N.G.; Galizio, N.C.; Rodrigues, M.S.; Almeida, H.F.; Lopes, A.R.; Moises, M.N.; et al. Functional and Proteomic Characterization of Acanthophis antarcticus Venom: Evidence of Fibrinogenolytic and Serine Peptidase Inhibitory Activities. Toxins 2025, 17, 405. https://doi.org/10.3390/toxins17080405.
  • D’Amélio, F.; Vigerelli, H.; Araldi, R.P.; Batista, I.F.C.; Pimenta, D.C.; Kerkis, I. Comprehensive RNA-Seq Analysis of Human Osteoclast Function in Response to Bothrops moojeni Venom Fractions: Pathways of Bone Resorption and Cytoskeletal Disruption. Toxins 2025, 17, 358. https://doi.org/10.3390/toxins17070358.
  • Espín-Angulo, J.; Vela, D. Computational Modeling of Low-Abundance Proteins in Venom Gland Transcriptomes: Bothrops asper and Bothrops jararaca. Toxins 2025, 17, 262. https://doi.org/10.3390/toxins17060262.
  • Kuznetsov, V.G.; Melnikova, D.I.; Shabelnikov, S.V.; Magarlamov, T.Y. Proteotranscriptomic Profiling of the Toxic Mucus of Kulikovia alborostrata (Pilidiophora, Nemertea). Toxins 2024, 17, 5. https://doi.org/10.3390/toxins17010005.
  • Espín-Angulo, J.; Vela, D. Exploring the Venom Gland Transcriptome of Bothrops asper and Bothrops jararaca: De Novo Assembly and Analysis of Novel Toxic Proteins. Toxins 2024, 16, 511. https://doi.org/10.3390/toxins16120511.
  • Yang, C.; Ding, L.; He, Q.; Chen, X.; Zhu, H.; Chen, F.; Yang, W.; Pan, Y.; Tai, Z.; Zhang, W.; et al. Proteomic Profiling of Venoms from Bungarus suzhenae and B. bungaroides: Enzymatic Activities and Toxicity Assessment. Toxins 2024, 16, 494. https://doi.org/10.3390/toxins16110494.
  • Jiang, H.; Wang, Y.; Zhang, G.; Jia, A.; Wei, Z.; Wang, Y. Identification and Evolutionary Analysis of the Widely Distributed CAP Superfamily in Spider Venom. Toxins 2024, 16, 240. https://doi.org/10.3390/toxins16060240.
  • Saldarriaga-Córdoba, M.; Clavero-León, C.; Rey-Suarez, P.; Nuñez-Rangel, V.; Avendaño-Herrera, R.; Solano-González, S.; Alzate, J.F. Unveiling Novel Kunitz- and Waprin-Type Toxins in the Micrurus mipartitus Coral Snake Venom Gland: An In Silico Transcriptome Analysis. Toxins 2024, 16, 224. https://doi.org/10.3390/toxins16050224.
  • Bala, A.A.; Oukkache, N.; Sanchez, E.E.; Suntravat, M.; Galan, J.A. Venoms and Extracellular Vesicles: A New Frontier in Venom Biology. Toxins 2025, 17, 36. https://doi.org/10.3390/toxins17010036.
  • Roman-Ramos, H.; Ho, P.L. Current Technologies in Snake Venom Analysis and Applications. Toxins 2024, 16, 458. https://doi.org/10.3390/toxins16110458.

References

  1. Ching, A.T.; Rocha, M.M.; Paes Leme, A.F.; Pimenta, D.C.; de Fátima, D.; Furtado, M.; Serrano, S.M.; Ho, P.L.; Junqueira-de-Azevedo, I.L. Some aspects of the venom proteome of the Colubridae snake Philodryas olfersii revealed from a Duvernoy’s (venom) gland transcriptome. FEBS Lett. 2006, 580, 4417–4422. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  2. Valente, R.H.; Guimarães, P.R.; Junqueira, M.; Neves-Ferreira, A.G.; Soares, M.R.; Chapeaurouge, A.; Trugilho, M.R.; León, I.R.; Rocha, S.L.; Oliveira-Carvalho, A.L.; et al. Bothrops insularis venomics: A proteomic analysis supported by transcriptomic-generated sequence data. J. Proteom. 2009, 72, 241–255. [Google Scholar] [CrossRef] [Scilit]
  3. Corrêa-Netto, C.; Junqueira-de-Azevedo Ide, L.; Silva, D.A.; Ho, P.L.; Leitão-de-Araújo, M.; Alves, M.L.; Sanz, L.; Foguel, D.; Zingali, R.B.; Calvete, J.J. Snake venomics and venom gland transcriptomic analysis of Brazilian coral snakes, Micrurus altirostris and M. corallinus. J. Proteom. 2011, 74, 1795–1809. [Google Scholar] [CrossRef] [Scilit]
  4. Ching, A.T.; Paes Leme, A.F.; Zelanis, A.; Rocha, M.M.; Furtado Mde, F.; Silva, D.A.; Trugilho, M.R.; da Rocha, S.L.; Perales, J.; Ho, P.L.; et al. Venomics profiling of Thamnodynastes strigatus unveils matrix metalloproteinases and other novel proteins recruited to the toxin arsenal of rear-fanged snakes. J. Proteome Res. 2012, 11, 1152–1162. [Google Scholar] [CrossRef] [Scilit]
  5. Korolkova, Y.; Mikov, A.; Lobas, A.; Solovyeva, E.; Surin, A.; Andreev, Y.; Gorshkov, M.; Kozlov, S. Venom-gland transcriptomics and venom proteomics of the Tibellus oblongus spider. Sci. Data 2023, 10, 820. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  6. Scieuzo, C.; Salvia, R.; Franco, A.; Pezzi, M.; Cozzolino, F.; Chicca, M.; Scapoli, C.; Vogel, H.; Monti, M.; Ferracini, C.; et al. An integrated transcriptomic and proteomic approach to identify the main Torymus sinensis venom components. Sci. Rep. 2021, 11, 5032. [Google Scholar] [CrossRef] [Scilit]
  7. Santibáñez-López, C.E.; Cid-Uribe, J.I.; Batista, C.V.; Ortiz, E.; Possani, L.D. Venom Gland Transcriptomic and Proteomic Analyses of the Enigmatic Scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with Insights on the Evolution of Its Venom Components. Toxins 2016, 8, 367. [Google Scholar] [CrossRef] [Scilit]
  8. Yin, W.; You, Y.; Tembrock, L.R.; Zhang, M.; Li, Z.; Zheng, Y.; Zhao, Y.; Yang, Z. Transcriptomic and proteomic analyses reveals the diverse venom composition of the spider Neoscona shillongensis. Insect Biochem. Mol. Biol. 2025, 180, 104289. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  9. Hartigan, A.; Jaimes-Becerra, A.; Okamura, B.; Doonan, L.B.; Ward, M.; Marques, A.C.; Long, P.F. Recruitment of toxin-like proteins with ancestral venom function supports endoparasitic lifestyles of Myxozoa. PeerJ 2021, 9, e11208. [Google Scholar] [CrossRef] [Scilit]
  10. Modahl, C.M.; Frietze, S.; Mackessy, S.P. Transcriptome-facilitated proteomic characterization of rear-fanged snake venoms reveal abundant metalloproteinases with enhanced activity. J. Proteom. 2018, 187, 223–234. [Google Scholar] [CrossRef] [Scilit]
  11. Sunagar, K.; Khochare, S.; Senji Laxme, R.R.; Attarde, S.; Dam, P.; Suranse, V.; Khaire, A.; Martin, G.; Captain, A. A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India. Toxins 2021, 13, 69. [Google Scholar] [CrossRef] [Scilit]
  12. Safavi-Hemami, H.; Hu, H.; Gorasia, D.G.; Bandyopadhyay, P.K.; Veith, P.D.; Young, N.D.; Reynolds, E.C.; Yandell, M.; Olivera, B.M.; Purcell, A.W. Combined proteomic and transcriptomic interrogation of the venom gland of Conus geographus uncovers novel components and functional compartmentalization. Mol. Cell Proteom. 2014, 13, 938–953. [Google Scholar] [CrossRef] [Scilit]
  13. Zancolli, G.; Reijnders, M.; Waterhouse, R.M.; Robinson-Rechavi, M. Convergent evolution of venom gland transcriptomes across Metazoa. Proc. Natl. Acad. Sci. USA 2022, 119, e2111392119. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  14. Junqueira-de-Azevedo, I.L.; Bastos, C.M.; Ho, P.L.; Luna, M.S.; Yamanouye, N.; Casewell, N.R. Venom-related transcripts from Bothrops jararaca tissues provide novel molecular insights into the production and evolution of snake venom. Mol. Biol. Evol. 2015, 32, 754–766. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  15. Zelanis, A.; Menezes, M.C.; Kitano, E.S.; Liberato, T.; Tashima, A.K.; Pinto, A.F.; Sherman, N.E.; Ho, P.L.; Fox, J.W.; Serrano, S.M. Proteomic identification of gender molecular markers in Bothrops jararaca venom. J. Proteom. 2016, 139, 26–37. [Google Scholar] [CrossRef] [Scilit]
  16. Vonk, F.J.; Casewell, N.R.; Henkel, C.V.; Heimberg, A.M.; Jansen, H.J.; McCleary, R.J.; Kerkkamp, H.M.; Vos, R.A.; Guerreiro, I.; Calvete, J.J.; et al. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. Proc. Natl. Acad. Sci. USA 2013, 110, 20651–20656. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  17. Almeida, D.D.; Viala, V.L.; Nachtigall, P.G.; Broe, M.; Gibbs, H.L.; Serrano, S.M.T.; Moura-da-Silva, A.M.; Ho, P.L.; Nishiyama, M.Y., Jr.; Junqueira-de-Azevedo, I.L.M. Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome. Proc. Natl. Acad. Sci. USA 2021, 118, e2015159118. [Google Scholar] [CrossRef] [Scilit]
  18. Isomoto, A.; Shoguchi, E.; Hisata, K.; Inoue, J.; Sun, Y.; Inaba, K.; Satoh, N.; Ogawa, T.; Shibata, H. Active Expression of Genes for Protein Modification Enzymes in Habu Venom Glands. Toxins 2022, 14, 300. [Google Scholar] [CrossRef] [Scilit]
  19. Andrade-Silva, D.; Rosa-Fernandes, L.; Reis, M.S.; Chaves, A.F.A.; Trevisan-Silva, D.; Cardoso, S.R.T.; Palmisano, G.; Larsen, M.R.; Serrano, S.M.T. N-Glycoproteomic Portraits of Bothrops Snake Venoms Reveal Evolutionarily Conserved and Divergent Phenotypes. J. Proteome Res. 2025, 24, 5948–5972. [Google Scholar] [CrossRef] [Scilit]
  20. Georgieva, D.; Seifert, J.; Öhler, M.; von Bergen, M.; Spencer, P.; Arni, R.K.; Genov, N.; Betzel, C. Pseudechis australis venomics: Adaptation for a defense against microbial pathogens and recruitment of body transferrin. J. Proteome Res. 2011, 10, 2440–2464. [Google Scholar] [CrossRef] [Scilit]
  21. Soares, M.R.; Oliveira-Carvalho, A.L.; Wermelinger, L.S.; Zingali, R.B.; Ho, P.L.; Junqueira-de-Azevedo, I.L.; Diniz, M.R. Identification of novel bradykinin-potentiating peptides and C-type natriuretic peptide from Lachesis muta venom. Toxicon 2005, 46, 31–38. [Google Scholar] [CrossRef] [Scilit] [PubMed]
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