scholarly journals “Beyond Primary Sequence”—Proteomic Data Reveal Complex Toxins in Cnidarian Venoms

2019 ◽  
Vol 59 (4) ◽  
pp. 777-785 ◽  
Author(s):  
Adrian Jaimes-Becerra ◽  
Ranko Gacesa ◽  
Liam B Doonan ◽  
Ashlie Hartigan ◽  
Antonio C Marques ◽  
...  
Keyword(s):  
Adaptive Significance ◽  
Proteomic Data ◽  
Body Regions ◽  
Venomous Animals ◽  
Venom Composition ◽  
Toxin Protein ◽  
Clustering Approach ◽  
Venom Evolution ◽  
Present Understanding ◽  
Dual Functions

Abstract Venomous animals can deploy toxins for both predation and defense. These dual functions of toxins might be expected to promote the evolution of new venoms and alteration of their composition. Cnidarians are the most ancient venomous animals but our present understanding of their venom diversity is compromised by poor taxon sampling. New proteomic data were therefore generated to characterize toxins in venoms of a staurozoan, a hydrozoan, and an anthozoan. We then used a novel clustering approach to compare venom diversity in cnidarians to other venomous animals. Comparison of the presence or absence of 32 toxin protein families indicated venom composition did not vary widely among the 11 cnidarian species studied. Unsupervised clustering of toxin peptide sequences suggested that toxin composition of cnidarian venoms is just as complex as that in many venomous bilaterians, including marine snakes. The adaptive significance of maintaining a complex and relatively invariant venom remains unclear. Future study of cnidarian venom diversity, venom variation with nematocyst types and in different body regions are required to better understand venom evolution.

scholarly journals Machine learning can differentiate venom toxins from other proteins having non-toxic physiological functions

2016 ◽  
Vol 2 ◽  
pp. e90 ◽  
Author(s):  
Ranko Gacesa ◽  
David J. Barlow ◽  
Paul F. Long
Keyword(s):  
Machine Learning ◽  
Sequence Data ◽  
Biological Data ◽  
Biological Databases ◽  
Web Based ◽  
Physiological Functions ◽  
Link Type ◽  
Venom Toxins ◽  
Venomous Animals ◽  
Toxin Protein

Ascribing function to sequence in the absence of biological data is an ongoing challenge in bioinformatics. Differentiating the toxins of venomous animals from homologues having other physiological functions is particularly problematic as there are no universally accepted methods by which to attribute toxin function using sequence data alone. Bioinformatics tools that do exist are difficult to implement for researchers with little bioinformatics training. Here we announce a machine learning tool called ‘ToxClassifier’ that enables simple and consistent discrimination of toxins from non-toxin sequences with >99% accuracy and compare it to commonly used toxin annotation methods. ‘ToxClassifer’ also reports the best-hit annotation allowing placement of a toxin into the most appropriate toxin protein family, or relates it to a non-toxic protein having the closest homology, giving enhanced curation of existing biological databases and new venomics projects. ‘ToxClassifier’ is available for free, either to download (https://github.com/rgacesa/ToxClassifier) or to use on a web-based server (http://bioserv7.bioinfo.pbf.hr/ToxClassifier/).

scholarly journals Co-option of the same ancestral gene family gave rise to mammalian and reptilian toxins

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Agneesh Barua ◽  
Ivan Koludarov ◽  
Alexander S. Mikheyev
Keyword(s):  
Phylogenetic Analysis ◽  
Serine Proteases ◽  
Biochemical Activity ◽  
Ancestral Gene ◽  
The Core ◽  
Venomous Animals ◽  
Regulatory Architecture ◽  
Vasodilatory Activity ◽  
Venom Evolution ◽  
Shared Genetic

Abstract Background Evolution can occur with surprising predictability when organisms face similar ecological challenges. For most traits, it is difficult to ascertain whether this occurs due to constraints imposed by the number of possible phenotypic solutions or because of parallel responses by shared genetic and regulatory architecture. Exceptionally, oral venoms are a tractable model of trait evolution, being largely composed of proteinaceous toxins that have evolved in many tetrapods, ranging from reptiles to mammals. Given the diversity of venomous lineages, they are believed to have evolved convergently, even though biochemically similar toxins occur in all taxa. Results Here, we investigate whether ancestral genes harbouring similar biochemical activity may have primed venom evolution, focusing on the origins of kallikrein-like serine proteases that form the core of most vertebrate oral venoms. Using syntenic relationships between genes flanking known toxins, we traced the origin of kallikreins to a single locus containing one or more nearby paralogous kallikrein-like clusters. Additionally, phylogenetic analysis of vertebrate serine proteases revealed that kallikrein-like toxins in mammals and reptiles are genetically distinct from non-toxin ones. Conclusions Given the shared regulatory and genetic machinery, these findings suggest that tetrapod venoms evolved by co-option of proteins that were likely already present in saliva. We term such genes ‘toxipotent’—in the case of salivary kallikreins they already had potent vasodilatory activity that was weaponized by venomous lineages. Furthermore, the ubiquitous distribution of kallikreins across vertebrates suggests that the evolution of envenomation may be more common than previously recognized, blurring the line between venomous and non-venomous animals.

scholarly journals An ancient, conserved gene regulatory network led to the rise of oral venom systems

2020 ◽  
Author(s):  
Agneesh Barua ◽  
Alexander S. Mikheyev
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Housekeeping Genes ◽  
Venom Gland ◽  
Venomous Animals ◽  
Molecular Machinery ◽  
Venom Evolution ◽  
Gene Regulatory ◽  
Conserved Gene

AbstractOral venom systems evolved multiple times in numerous vertebrates enabling exploitation of unique predatory niches. Yet how and when they evolved remains poorly understood. Up to now, most research on venom evolution has focussed strictly on the toxins. However, using toxins present in modern day animals to trace the origin of the venom system is difficult, since they tend to evolve rapidly, show complex patterns of expression, and were incorporated into the venom arsenal relatively recently. Here we focus on gene regulatory networks associated with the production of toxins in snakes, rather than the toxins themselves. We found that overall venom gland gene expression was surprisingly well conserved when compared to salivary glands of other amniotes. We characterised the ‘meta-venom’, a network of approximately 3000 non-secreted housekeeping genes that are strongly co-expressed with the toxins, and are primarily involved in protein folding and modification. Conserved across amniotes, this network was co-opted for venom evolution by exaptation of existing members and the recruitment of new toxin genes. For instance, starting from this common molecular foundation, Heloderma lizards, shrews, and solenodon, evolved venoms in parallel by overexpression of kallikreins, which were common in ancestral saliva and induce vasodilation when injected, causing circulatory shock. Derived venoms, such as those of snakes, incorporated novel toxins, though still rely on hypotension for prey immobilization. These similarities suggest repeated co-option of shared molecular machinery for the evolution of oral venom in mammals and reptiles, blurring the line between truly venomous animals and their ancestors.

scholarly journals Proteomic Characterization of the Venom Of Five Bombus (Thoracobombus) Species

2017 ◽  
Author(s):  
Nezahat Pinar Barkan ◽  
Mustafa Bilal Bayazit ◽  
Duygu Demiralp Özel
Keyword(s):  
Laser Desorption ◽  
Bumble Bee ◽  
Laser Desorption Ionization ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
Venomous Animals ◽  
Venom Composition ◽  
Proteomic Techniques ◽  
Proteins And Peptides

AbstractVenomous animals use venom; a complex biofluid composed of unique mixtures of proteins and peptides, to act on vital systems of the prey or predator. In bees, venom is solely used for defense against predators. However, the venom composition of bumble bees (Bombus sp.) is largely unknown. Thoracobombus subgenus of Bombus sp. is a diverse subgenus represented by 14 members across Turkey. In this study, we sought out to proteomically characterize the venom of five Thoracobombus species by using bottom-up proteomic techniques. We have obtained two-dimensional polyacrylamide gel (2D-PAGE) images of each venom sample. We have subsequently identified the protein spots by using matrix assisted laser desorption ionization / time of flight mass spectrometry (MALDI-TOF MS). We have identified 47 proteins for Bombus humilis; 32 for B. pascuorum, 60 for B. ruderarius; 39 for B. sylvarum and 35 for B. zonatus. Our analyses provide the primary proteomic characterization of five bumble bee species’ venom composition.

scholarly journals Dietary Breadth is Positively Correlated with Venom Complexity in Cone Snails

2015 ◽  
Author(s):  
Mark A Phuong ◽  
Gusti N Mahardika ◽  
Michael E Alfaro
Keyword(s):  
Evolutionary Dynamics ◽  
Gene Diversity ◽  
Expression Patterns ◽  
Snail Species ◽  
Ecological Data ◽  
Dietary Breadth ◽  
Venom Composition ◽  
Taxonomic Class ◽  
Venom Evolution ◽  
Cone Snails

Although diet is believed to be a major factor underlying the evolution of venom, few comparative studies examine both venom composition and diet across a radiation of venomous species. Cone snails within the family, Conidae, comprise more than 700 species of carnivorous marine snails that capture their prey by using a cocktail of venomous neurotoxins (conotoxins or conopeptides). Venom composition across species has been previously hypothesized to be shaped by (a) prey taxonomic class (i.e., worms, molluscs, or fish) and (b) dietary breadth. We tested these hypotheses under a comparative phylogenetic framework using ecological data in conjunction with venom duct transcriptomes sequenced from 12 phylogenetically disparate cone snail species, including 10 vermivores (worm-eating), one molluscivore, and one generalist. We discovered 2223 unique conotoxin precursor peptides that encoded 1864 unique mature toxins across all species, >90% of which are new to this study. In addition, we identified two novel gene superfamilies and 16 novel cysteine frameworks. Each species exhibited unique venom profiles, with venom composition and expression patterns among species dominated by a restricted set of gene superfamilies and mature toxins. In contrast with the dominant paradigm for interpreting Conidae venom evolution, prey taxonomic class did not predict venom composition patterns among species. Our results suggests that cone snails have either evolved species-specific expression patterns likely as a consequence of the rapid evolution of conotoxin genes, or that traditional means of categorizing prey type (i.e., worms, mollusc, or fish) and conotoxins (i.e., by gene superfamily) do not accurately encapsulate evolutionary dynamics between diet and venom composition. We also found a significant positive relationship between dietary breadth and measures of conotoxin complexity. These results indicate that species with more generalized diets tend to have more complex venoms and utilize a greater number of venom genes for prey capture. Whether this increased gene diversity confers an increased capacity for evolutionary change remains to be tested. Overall, our results corroborate the key role of diet in influencing patterns of venom evolution in cone snails and other venomous radiations.

scholarly journals Changes in predator exposure, but not in diet, induce phenotypic plasticity in scorpion venom

2017 ◽  
Vol 284 (1863) ◽  
pp. 20171364 ◽  
Author(s):  
Alex N. Gangur ◽  
Michael Smout ◽  
Michael J. Liddell ◽  
Jamie E. Seymour ◽  
David Wilson ◽  
...  
Keyword(s):  
Scorpion Venom ◽  
Relative Increase ◽  
Trophic Levels ◽  
Adaptive Plasticity ◽  
Arms Races ◽  
Invertebrate Prey ◽  
Venomous Animals ◽  
Venom Composition ◽  
The Stability ◽  
Dead Prey

Animals embedded between trophic levels must simultaneously balance pressures to deter predators and acquire resources. Venomous animals may use venom toxins to mediate both pressures, and thus changes in this balance may alter the composition of venoms. Basic theory suggests that greater exposure to a predator should induce a larger proportion of defensive venom components relative to offensive venom components, while increases in arms races with prey will elicit the reverse. Alternatively, reducing the need for venom expenditure for food acquisition, for example because of an increase in scavenging, may reduce the production of offensive venom components. Here, we investigated changes in scorpion venom composition using a mesocosm experiment where we manipulated scorpions' exposure to a surrogate vertebrate predator and live and dead prey. After six weeks, scorpions exposed to surrogate predators exhibited significantly different venom chemistry compared with naive scorpions. This change included a relative increase in some compounds toxic to vertebrate cells and a relative decrease in some compounds effective against their invertebrate prey. Our findings provide, to our knowledge, the first evidence for adaptive plasticity in venom composition. These changes in venom composition may increase the stability of food webs involving venomous animals.

scholarly journals The parallel origins of vertebrate venoms

2021 ◽  
Author(s):  
Agneesh Barua ◽  
Ivan Koludarov ◽  
Alexander S. Mikheyev
Keyword(s):  
Phylogenetic Analysis ◽  
Comparative Genomics ◽  
Gene Cluster ◽  
Serine Proteases ◽  
Evolutionary Biology ◽  
Central Question ◽  
Venomous Snake ◽  
The Core ◽  
Venomous Animals ◽  
Venom Evolution

AbstractEvolution can occur with surprising predictability when faced with similar ecological challenges. How and why this repeatability occurs remains a central question in evolutionary biology, but the complexity of most traits makes it challenging to answer. Reptiles and mammals independently evolved oral venoms that consist of proteinaceous cocktails which allow straightforward mapping between genotype and phenotype. Although biochemically similar toxins can occur as major venom components across many taxa, whether these toxins evolved via convergent or parallel means remains unknown. Most notable among them are kallikrein-like serine proteins, which form the core of most vertebrate venoms, and are employed by all venomous snake families. Here we used a combination of comparative genomics and phylogenetics to investigate whether serine protease recruitment into the venom occurred independently or in parallel across the different tetrapod lineages. Using syntenic relationships between genes flanking known toxins, we traced the origin of kallikreins to a single locus containing one or more nearby paralogous kallikrein-like clusters. Independently, phylogenetic analysis of vertebrate serine proteases revealed that the same gene cluster gave rise to toxins in mammals and reptiles. Given the shared regulatory and genetic machinery underlying venom evolution, these findings suggest a unified model underlying vertebrate venom evolution by exaptation of homologous ancestral kallikreins. Furthermore, the ubiquitous distribution of kallikreins across vertebrates suggests that the evolution of envenomation may be more common than previously recognized, blurring the line between venomous and non-venomous animals.

scholarly journals An ancient, conserved gene regulatory network led to the rise of oral venom systems

2021 ◽  
Vol 118 (14) ◽  
pp. e2021311118
Author(s):  
Agneesh Barua ◽  
Alexander S. Mikheyev
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Housekeeping Genes ◽  
Venom Gland ◽  
Venomous Animals ◽  
Molecular Machinery ◽  
Venom Evolution ◽  
Gene Regulatory ◽  
Conserved Gene

Oral venom systems evolved multiple times in numerous vertebrates enabling the exploitation of unique predatory niches. Yet how and when they evolved remains poorly understood. Up to now, most research on venom evolution has focused strictly on the toxins. However, using toxins present in modern day animals to trace the origin of the venom system is difficult, since they tend to evolve rapidly, show complex patterns of expression, and were incorporated into the venom arsenal relatively recently. Here we focus on gene regulatory networks associated with the production of toxins in snakes, rather than the toxins themselves. We found that overall venom gland gene expression was surprisingly well conserved when compared to salivary glands of other amniotes. We characterized the “metavenom network,” a network of ∼3,000 nonsecreted housekeeping genes that are strongly coexpressed with the toxins, and are primarily involved in protein folding and modification. Conserved across amniotes, this network was coopted for venom evolution by exaptation of existing members and the recruitment of new toxin genes. For instance, starting from this common molecular foundation, Heloderma lizards, shrews, and solenodon, evolved venoms in parallel by overexpression of kallikreins, which were common in ancestral saliva and induce vasodilation when injected, causing circulatory shock. Derived venoms, such as those of snakes, incorporated novel toxins, though still rely on hypotension for prey immobilization. These similarities suggest repeated cooption of shared molecular machinery for the evolution of oral venom in mammals and reptiles, blurring the line between truly venomous animals and their ancestors.

Radiation Damage in Ceramics

1982 ◽  
Vol 40 ◽  
pp. 600-603
Author(s):  
T. E. Mitchell ◽  
M. R. Pascucci ◽  
R. A. Youngman
Keyword(s):  
Radiation Damage ◽  
Outer Space ◽  
Point Of View ◽  
Nuclear Waste Storage ◽  
Waste Storage ◽  
Storage Media ◽  
Transmission Electron ◽  
Fundamental Point ◽  
Small Defect ◽  
Present Understanding

1. Introduction. Studies of radiation damage in ceramics are of interest not only from a fundamental point of view but also because it is important to understand the behavior of ceramics in various practical radiation enyironments- fission and fusion reactors, nuclear waste storage media, ion-implantation devices, outer space, etc. A great deal of work has been done on the spectroscopy of point defects and small defect clusters in ceramics, but relatively little has been performed on defect agglomeration using transmission electron microscopy (TEM) in the same kind of detail that has been so successful in metals. This article will assess our present understanding of radiation damage in ceramics with illustrations using results obtained from the authors' work.

Molecular Mechanism of Apoptosis Induction by Resveratrol, a Natural Cancer Chemopreventive Agent

2008 ◽  
Vol 78 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Fan ◽  
Jiang ◽  
Zhang ◽  
Bai
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanism ◽  
Apoptosis Induction ◽  
Protective Agents ◽  
Chemopreventive Agent ◽  
Naturally Occurring ◽  
Apoptosis Pathways ◽  
Present Understanding

In efforts to identify naturally occurring compounds that act as protective agents, resveratrol, a phytoalexin existing in wine, has attracted much interest because of its diverse pharmacological characteristics. Considering that apoptosis induction is the most potent defense approach for cancer treatment, we have tried to summarize our present understanding of apoptosis induction by resveratrol based on the two major apoptosis pathways.

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