Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution

Modahl, Cassandra M.; Mackessy, Stephen P.

doi:10.1371/journal.pntd.0004587

Cited by 30 publications

(28 citation statements)

References 67 publications

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“…However, it has been shown that mRNA encoding toxins can be recovered from the venom of several species[ 22 ]. Subsequent studies have supported this finding and showed its applicability to RNA-based venom studies[ 23 , 24 ].…”

Section: Omics In Venom Researchmentioning

confidence: 72%

Modern trends in animal venom research - omics and nanomaterials

Utkin

2017

WJBC

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Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin - a toxin in scorpion venom, which has been shown to bind specifically to glioma cells - are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and nanotechnologies in venom research are systematized concisely in this paper.

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Section: Omics In Venom Researchmentioning

confidence: 72%

Modern trends in animal venom research - omics and nanomaterials

Utkin

2017

WJBC

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“…exist in the venom, likely in an inactivated state [41], but it is currently unknown if degradation of venom DNA occurs due to their actions. However, in addition to DNA, intact mRNA has been purified from venom [42], indicating overall stability of nucleic acids in the venom gland and in dried venom despite possible degradation via DNases and RNases found in venom.…”

Section: Resultsmentioning

confidence: 99%

DNA Barcodes from Snake Venom: a Broadly Applicable Method for Extraction of DNA from Snake Venoms

2018

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DNA barcoding is a simple technique used to develop a large-scale system of classification that is broadly applicable across a wide variety of taxa. DNA-based analysis of snake venoms can provide a system of classification independent of currently accepted taxonomic relationships by generating DNA barcodes specific to each venom sample. DNA purification from dried snake venoms has previously required large amounts of starting material, has resulted in low yields and inconsistent amplification, and was possible with front-fanged snakes only. Here, we present a modified DNA extraction protocol applied to venoms of both front- and rear-fanged snakes that requires significantly less starting material (1mg) and yields sufficient amounts of DNA for successful PCR amplification of regions commonly used for DNA barcoding.

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“…While present in the venoms of multiple snake families, 3FTx are at their highest relative abundance in the families Colubridae and Elapidae [18,44]. This broad trend holds true in the genus Boiga, with various studies finding that 3FTx are the predominant toxins in their venoms [44,[106][107][108].…”

Section: Introductionmentioning

confidence: 99%

“…and Mackessy[107] suggested, based on sequence similarity, that the presence of such dimers in B. cynodon venom is likely. However, this study did not explore whether the newly-evolved cysteines characteristic of irditoxin were present in the sequences of species outside of B. irregularis.…”

mentioning

confidence: 99%

“…the significance of these cysteines.Modahl and Mackessy [107] discussed the similarity of their two B. cynodon sequences to irditoxin A (Boiga cynodon A0A193CHL1, 83% identical) and B (Boiga cynodon A0A193CHL2, 93% identical), however only the sequence similar to the B subunit actually contained the characteristic cysteine and the presence of this cysteine was not commented upon. Modahl and Mackessy[107] also published-but did not discuss-a B. nigriceps sequence that…”

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confidence: 99%

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Novelty in three-finger toxin evolution

Dashevsky¹

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Snakes are a striking taxon on many levels and have an indelible place in the collective culture of humanity. This is due to a number of unusual features including their limblessness, ability to ingest large prey, but most importantly their venom. From a biological perspective, snakes are equally fascinating, showing how a simple body plan can be used to great effect in an extremely broad variety of niches. Snakes are globally distributed and ecologically diverse; as a result, since recent research has shown that most snakes are venomous to some degree, their venom is equally diverse. This thesis focuses on one major toxin family: three-finger toxins (3FTx). These toxins can be found in virtually all venomous snake lineages and are often neurotoxic. Since their original recruitment there have been numerous instances of structural and functional innovation within this toxin family. The research in this thesis pertains to several such novel adaptations in snakes of the colubrid and elapid families, many of whose venom is composed primarily of these toxins. Chapter 2 deals with the ancestral version 3FTx and how, in the colubrine genus Boiga, simple mutations in toxins can lead to structural changes, in this case additional cysteines enable the formation of dimeric toxins with increased potency. These novel toxins can, in turn, open up new niches to the snakes which possess those toxins. In B. irregularis they facilitated a destructive invasion event and may have similarly assisted in the spread of an ancestral Boiga since our research shows that several other species possess similar dimeric toxins. This echoes a process that occurred in the ancestor of the elapids where the loss of a pair of cysteines and their disulfide bond was followed by an incredible diversification of these toxins and the snakes that produce them. Chapter 3 explores venom composition and activity of the genus Calliophis, the most basal genus of the elapids. C. bivirgatus and C. intestinalis both possess extremely elongated venom glands and each produce 3FTx with novel sodium channel toxicity. However, the two venoms produce opposite effects from one another. These results suggests some intriguing possibilities about the evolutionary history of these novel traits in Calliophis and the general composition of their venoms inform our understanding of how the venoms of more derived elapids evolved.Chapters 4 and 5 focus on the genus Micrurus. This genus from the Americas is by far the most speciose genus of elapids and belongs to the coral snake clade which is the next branch in the phylogeny of the elapids after Calliophis. The venoms of these snakes all contain a high number of unique 3FTx, though some venoms may be dominated by PLA2 toxins in terms of overall composition. Chapter 4 focuses on the sequence diversity of 3FTx from this genus and the selection regimes under which they operate. This diversity may lay the groundwork for rapid changes in the toxin composition of the venom and accompanying changes in venom activity. Chapter 5 directly ...

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Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution

Cited by 30 publications

References 67 publications

Modern trends in animal venom research - omics and nanomaterials

Modern trends in animal venom research - omics and nanomaterials

DNA Barcodes from Snake Venom: a Broadly Applicable Method for Extraction of DNA from Snake Venoms

Novelty in three-finger toxin evolution

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