Venom Before Specialisation? A Layered Assessment of Early Venom Evolution in Lizards and Snakes.
- 1Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia.
Abstract
Debate over the origin of squamate venom is frequently distorted by treating molecular availability, toxin recruitment and secretion, functional venom, and delivery-system elaboration as a single evolutionary event. This review separates these transitions and reassesses early venom evolution in anguimorph lizards and snakes using anatomical, molecular, proteomic, functional, ecological, and phylogenetic evidence. The species-level ancestral-state reconstructions of a recent Wüster, Modahl, and Arbuckle manuscript are internally robust to the four coding schemes tested and accommodate uncertain tips and reversible venom loss. Their inference nevertheless remains conditional on a binary definition of observed functional venom, a single hidden precursor category, a homogeneous transition process, and non-caenophidian snake states that were not varied in the relevant sensitivity analyses. While they coded two origins of venom within Anguimorpha, gland anatomy and derived oral products make an early functional origin followed by retention, reduction, loss, and parallel elaboration a strongly supported alternate hypothesis. However, as critical bridge taxa lack direct evidence of natural delivery, realistic dose, or secretion-specific fitness benefit, resolution of the history remains unresolved. For Heloderma, field studies of H. suspectum and H. horridum, together with painful, prolonged defensive bites, support a defensive role, although its primacy (to the exclusion of an additional predatory function) as advocated by them is sensitive to observational bias. Neurotoxic, cardiovascular, and coagulotoxic activities make a predatory contribution supported, leaving the original selective driver unresolved. Within Serpentes, their placement of venom at the base of the Caenophidia is challenged by distributed maxillary, mandibular, and rictal glands and derived oral products in non-caenophidian taxa, making an origin before Caenophidia a viable alternative hypothesis. Derived mucous systems in boas and pythons and specialised Scolecophidia cannot alone polarise the ancestral snake state. Current evidence is therefore insufficient to distinguish one shared functional origin from two functionalisations of a homologous ancestral oral secretory system. No alternative comparative reconstruction is performed; the review shows only that earlier origins remain viable and categorical absence coding is insufficiently secure for several poorly investigated taxa. Resolution requires matched gland cell biology, orthology- and synteny-resolved genomics, quantitative secretion proteomics, realistic functional assays, secretion-specific ecological tests, broader Iguania and non-caenophidian snake sampling, and ancestral-state models that represent graded evidence, both false-negative and false-positive classification, reduction, loss, and phylogenetic uncertainty.
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BibTeX
@article{fry2026venom,
title = {{Venom Before Specialisation? A Layered Assessment of Early Venom Evolution in Lizards and Snakes.}},
author = {Bryan G Fry},
journal = {Toxins},
year = {2026},
month = sep,
doi = {10.3390/toxins18100409},
url = {https://europepmc.org/article/MED/42931500},
note = {CC BY},
}
RIS
TY - JOUR
TI - Venom Before Specialisation? A Layered Assessment of Early Venom Evolution in Lizards and Snakes.
AU - Bryan G Fry
PY - 2026
DA - 2026/09/23
JO - Toxins
DO - 10.3390/toxins18100409
UR - https://europepmc.org/article/MED/42931500
AB - Debate over the origin of squamate venom is frequently distorted by treating molecular availability, toxin recruitment and secretion, functional venom, and delivery-system elaboration as a single evolutionary event. This review separates these transitions and reassesses early venom evolution in anguimorph lizards and snakes using anatomical, molecular, proteomic, functional, ecological, and phylogenetic evidence. The species-level ancestral-state reconstructions of a recent Wüster, Modahl, and Arbuckle manuscript are internally robust to the four coding schemes tested and accommodate uncertain tips and reversible venom loss. Their inference nevertheless remains conditional on a binary definition of observed functional venom, a single hidden precursor category, a homogeneous transition process, and non-caenophidian snake states that were not varied in the relevant sensitivity analyses. While they coded two origins of venom within Anguimorpha, gland anatomy and derived oral products make an early functional origin followed by retention, reduction, loss, and parallel elaboration a strongly supported alternate hypothesis. However, as critical bridge taxa lack direct evidence of natural delivery, realistic dose, or secretion-specific fitness benefit, resolution of the history remains unresolved. For Heloderma, field studies of H. suspectum and H. horridum, together with painful, prolonged defensive bites, support a defensive role, although its primacy (to the exclusion of an additional predatory function) as advocated by them is sensitive to observational bias. Neurotoxic, cardiovascular, and coagulotoxic activities make a predatory contribution supported, leaving the original selective driver unresolved. Within Serpentes, their placement of venom at the base of the Caenophidia is challenged by distributed maxillary, mandibular, and rictal glands and derived oral products in non-caenophidian taxa, making an origin before Caenophidia a viable alternative hypothesis. Derived mucous systems in boas and pythons and specialised Scolecophidia cannot alone polarise the ancestral snake state. Current evidence is therefore insufficient to distinguish one shared functional origin from two functionalisations of a homologous ancestral oral secretory system. No alternative comparative reconstruction is performed; the review shows only that earlier origins remain viable and categorical absence coding is insufficiently secure for several poorly investigated taxa. Resolution requires matched gland cell biology, orthology- and synteny-resolved genomics, quantitative secretion proteomics, realistic functional assays, secretion-specific ecological tests, broader Iguania and non-caenophidian snake sampling, and ancestral-state models that represent graded evidence, both false-negative and false-positive classification, reduction, loss, and phylogenetic uncertainty.
SN - 2072-6651
ER -