Dataset Information

Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms.

ABSTRACT: While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability. Examination of other toxin types also revealed similar variability in their presence and activity levels. The high level of venom chemistry variation in varanid lizards compared to that of helodermatid lizards suggests that venom may be subject to different selection pressures in these two families. These results not only contribute to our understanding of venom evolution but also reveal anguimorph lizard venoms to be rich sources of novel bioactive molecules with potential as drug design and development lead compounds.

SUBMITTER: Koludarov I

PROVIDER: S-EPMC5577576 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms.

Koludarov Ivan I Jackson Timothy Nw TN Brouw Bianca Op den BOD Dobson James J Dashevsky Daniel D Arbuckle Kevin K Clemente Christofer J CJ Stockdale Edward J EJ Cochran Chip C Debono Jordan J Stephens Carson C Panagides Nadya N Li Bin B Manchadi Mary-Louise Roy MR Violette Aude A Fourmy Rudy R Hendrikx Iwan I Nouwens Amanda A Clements Judith J Martelli Paolo P Kwok Hang Fai HF Fry Bryan G BG

Toxins 20170806 8

While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquit ...[more]

PMID: 28783084

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Project description:Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ?130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained highlight the importance of utilizing evolution-based search strategies for biodiscovery and emphasize the largely untapped drug design and development potential of lizard venoms.

Project description:Anguimorpha, within the order Squamata, represents a group with distinct morphological and behavioral characteristics in different ecological niches among lizards. Within Anguimorpha, there is a group characterized by limb loss, occupying lower ecological niches, concentrated within the subfamily Anguinae. Lizards with limbs and those without exhibit distinct locomotor abilities when adapting to their habitats, which in turn necessitate varying degrees of energy expenditure. Mitochondria, known as the metabolic powerhouses of cells, play a crucial role in providing approximately 95% of an organism's energy. Functionally, mitogenomes (mitochondrial genomes) can serve as a valuable tool for investigating potential adaptive evolutionary selection behind limb loss in reptiles. Due to the variation of mitogenome structures among each species, as well as its simple genetic structure, maternal inheritance, and high evolutionary rate, the mitogenome is increasingly utilized to reconstruct phylogenetic relationships of squamate animals. In this study, we sequenced the mitogenomes of two species within Anguimorpha as well as the mitogenomes of two species in Gekkota and four species in Scincoidea. We compared these data with the mitogenome content and evolutionary history of related species. Within Anguimorpha, between the mitogenomes of limbless and limbed lizards, a branch-site model analysis supported the presence of 10 positively selected sites: Cytb protein (at sites 183 and 187), ND2 protein (at sites 90, 155, and 198), ND3 protein (at site 21), ND5 protein (at sites 12 and 267), and ND6 protein (at sites 72 and 119). These findings suggested that positive selection of mitogenome in limbless lizards may be associated with the energy requirements for their locomotion. Additionally, we acquired data from 205 mitogenomes from the NCBI database. Bayesian inference (BI) and Maximum Likelihood (ML) trees were constructed using the 13 mitochondrial protein-coding genes (PCGs) and two rRNAs (12S rRNA and 16S rRNA) from 213 mitogenomes. Our phylogenetic tree and the divergence time estimates for Squamata based on mitogenome data are consistent with results from previous studies. Gekkota was placed at the root of Squamata in both BI and ML trees. However, within the Toxicofera clade, due to long-branch attraction, Anguimorpha and (Pleurodonta + (Serpentes + Acrodonta)) were closely related groupings, which might indicate errors and also demonstrate that mitogenome-based phylogenetic trees may not effectively resolve long-branch attraction issues. Additionally, we reviewed the origin and diversification of Squamata throughout the Mesozoic era, suggesting that Squamata originated in the Late Triassic (206.05 Mya), with the diversification of various superfamilies occurring during the Cretaceous period. Future improvements in constructing squamate phylogenetic relationships using mitogenomes will rely on identifying snake and acrodont species with slower evolutionary rates, ensuring comprehensive taxonomic coverage of squamate diversity, and increasing the number of genes analyzed.

Dataset Information

Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms.

Publications

Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms.

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