Dynamic evolution of venom proteins in squamate reptiles

Casewell, Nicholas R.; Huttley, Gavin A.; Wüster, Wolfgang

doi:10.1038/ncomms2065

Cited by 99 publications

(76 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This result provided evidence that these toxin genes had undergone a gene duplication process in centipede that resulted in the expansion of multilocus venom gene families. This process was consistent with a similar phenomenon observed in snakes in previous reports (36,37).…”

Section: Discussionsupporting

confidence: 81%

Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede

Zhao

Lan

et al. 2018

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

SummaryCentipedes are one of the oldest venomous animals and use their venoms as weapons to attack prey or protect themselves. Their venoms contain various components with different biomedical and pharmacological properties. However, little attention has been paid to the profiles and diversity of their toxin-like proteins/peptides. In this study, we used a proteotranscriptomic approach to uncover the diversity of centipede toxin-like proteins in Scolopendra subspinipes mutilans. Nine hundred twentythree and 6,736 peptides, which were separately isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS and deduced from their transcriptomes. Finally, 1,369 unique proteins were identified in the proteome, including 100 proteins that exhibited overlapping expression in venom and torso tissues. Of these proteins, at least 40 proteins were identified as venom toxin-like proteins. Meanwhile, transcriptome mining identified approximately 10-fold more toxin-like proteins and enabled the characterization of the precursor architecture of mature toxin-like peptides. Importantly, combined with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides (neurotoxins accounted for 50%) were expressed outside the venom gland and involved in gene recruitment processes. These findings highlight the extensive diversity of centipede toxin-like proteins and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins. Moreover, we are the first group to report the gene recruitment activity of venom toxin-like proteins in centipede, similar to snakes.

show abstract

Section: Discussionsupporting

confidence: 81%

Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede

Zhao

Lan

et al. 2018

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…S4). Venom toxins are thought to have been coopted from gene homologs with nontoxic physiological functions that are expressed in tissues other than the venom gland (14,15). Our analysis of tissue-specific transcriptomic data (12,(16)(17)(18) provides genome-scale confirmation that these venom genes have, indeed, been recruited from a wide variety of tissue types (SI Appendix, Table S2).…”

Section: Resultsmentioning

confidence: 55%

“…S7-S9), consistent with their low transcript abundance in the venom gland. These results suggest that lectins do not contribute to king cobra envenoming, which is in contrast to many other venomous snakes (1,27), and that their repeated recruitment to the accessory gland is associated with the subsequent evolution of unidentified, nontoxic functions (15).…”

Section: Figs S7-s9 Andmentioning

confidence: 91%

The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

Vonk

Casewell

Henkel

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

433

428

View full text Add to dashboard Cite

Significance Snake venoms are toxic protein cocktails used for prey capture. To investigate the evolution of these complex biological weapon systems, we sequenced the genome of a venomous snake, the king cobra, and assessed the composition of venom gland expressed genes, small RNAs, and secreted venom proteins. We show that regulatory components of the venom secretory system may have evolved from a pancreatic origin and that venom toxin genes were co-opted by distinct genomic mechanisms. After co-option, toxin genes important for prey capture have massively expanded by gene duplication and evolved under positive selection, resulting in protein neofunctionalization. This diverse and dramatic venom-related genomic response seemingly occurs in response to a coevolutionary arms race between venomous snakes and their prey.

show abstract

“…Typically, toxins are encoded by relatively few (approximately 5-10) multilocus gene families, with each family capable of producing related isoforms generated by gene duplication events occurring over evolutionary time (1,14,15). The birth and death model of gene evolution (16) is frequently invoked as the mechanism giving rise to venom gene paralogs, with evidence that natural selection acting on surface exposed residues of the resulting gene duplicates facilitates subfunctionalization/neofunctionalization of the encoded proteins (15,(17)(18)(19). The result of these processes is a complex suite of toxins that act synergistically to cause rapid prey death.…”

mentioning

confidence: 99%

Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

Casewell

Wagstaff

Wüster

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

283

256

View full text Add to dashboard Cite

Variation in venom composition is a ubiquitous phenomenon in snakes and occurs both interspecifically and intraspecifically. Venom variation can have severe outcomes for snakebite victims by rendering the specific antibodies found in antivenoms ineffective against heterologous toxins found in different venoms. The rapid evolutionary expansion of different toxin-encoding gene families in different snake lineages is widely perceived as the main cause of venom variation. However, this view is simplistic and disregards the understudied influence that processes acting on gene transcription and translation may have on the production of the venom proteome. Here, we assess the venom composition of six related viperid snakes and compare interspecific changes in the number of toxin genes, their transcription in the venom gland, and their translation into proteins secreted in venom. Our results reveal that multiple levels of regulation are responsible for generating variation in venom composition between related snake species. We demonstrate that differential levels of toxin transcription, translation, and their posttranslational modification have a substantial impact upon the resulting venom protein mixture. Notably, these processes act to varying extents on different toxin paralogs found in different snakes and are therefore likely to be as important as ancestral gene duplication events for generating compositionally distinct venom proteomes. Our results suggest that these processes may also contribute to altering the toxicity of snake venoms, and we demonstrate how this variability can undermine the treatment of a neglected tropical disease, snakebite.

show abstract

Dynamic evolution of venom proteins in squamate reptiles

Cited by 99 publications

References 50 publications

Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede

Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede

The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

Contact Info

Product

Resources

About