scholarly journals Venom of the Annulated Sea Snake Hydrophis cyanocinctus: A Biochemically Simple but Genetically Complex Weapon

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 548
Author(s):  
Hong-Yan Zhao ◽  
Yan Sun ◽  
Yu Du ◽  
Jia-Qi Li ◽  
Jin-Geng Lv ◽  
...  
Keyword(s):  
Marine Environment ◽  
De Novo ◽  
Venom Gland ◽  
Secretory Protein ◽  
Sea Snake ◽  
Sea Snakes ◽  
Venom Toxins ◽  
Low Toxicity ◽  
Venom Evolution ◽  
And Function

Given that the venom system in sea snakes has a role in enhancing their secondary adaption to the marine environment, it follows that elucidating the diversity and function of venom toxins will help to understand the adaptive radiation of sea snakes. We performed proteomic and de novo NGS analyses to explore the diversity of venom toxins in the annulated sea snake (Hydrophis cyanocinctus) and estimated the adaptive molecular evolution of the toxin-coding unigenes and the toxicity of the major components. We found three-finger toxins (3-FTxs), phospholipase A2 (PLA2) and cysteine-rich secretory protein (CRISP) in the venom proteome and 59 toxin-coding unigenes belonging to 24 protein families in the venom-gland transcriptome; 3-FTx and PLA2 were the most abundant families. Nearly half of the toxin-coding unigenes had undergone positive selection. The short- (i.p. 0.09 μg/g) and long-chain neurotoxin (i.p. 0.14 μg/g) presented fairly high toxicity, whereas both basic and acidic PLA2s expressed low toxicity. The toxicity of H. cyanocinctus venom was largely determined by the 3-FTxs. Our data show the venom is used by H. cyanocinctus as a biochemically simple but genetically complex weapon and venom evolution in H. cyanocinctus is presumably driven by natural selection to deal with fast-moving prey and enemies in the marine environment.

scholarly journals The genome of Shaw’s sea snake (Hydrophis curtus) reveals secondary adaptation to its marine environment

2020 ◽  
Author(s):  
Changjun Peng ◽  
Jin-Long Ren ◽  
Cao Deng ◽  
Dechun Jiang ◽  
Jichao Wang ◽  
...  
Keyword(s):  
Rapid Evolution ◽  
Venom Gland ◽  
Salt Glands ◽  
Protein Coding ◽  
Sea Snake ◽  
Sea Snakes ◽  
Genetic Mechanisms ◽  
Marine Adaptation ◽  
Genomic Regions ◽  
Adaptive Specializations

Abstract The transition of terrestrial snakes to marine life approximately 10 million years ago (Ma) is ideal for exploring adaptive evolution. Sea snakes possess phenotype specializations including laterally compressed bodies, paddle-shaped tails, valvular nostrils, cutaneous respiration, elongated lungs and salt glands yet knowledge on the genetic underpinnings of the transition remain limited. Herein, we report the first genome of Shaw’s sea snake (Hydrophis curtus) and use it to investigate sea snake secondary marine adaptation. A hybrid assembly strategy obtains a high quality genome. Gene family analyses date a pulsed coding-gene expansion to about 20 Ma, and these genes associate strongly with adaptations to marine environments. Analyses of selection pressure and convergent evolution discover the rapid evolution of protein-coding genes, and some convergent features. Additionally, 108 conserved non-coding elements appear to have evolved quickly, and these may underpin the phenotypic changes. Transposon elements may contribute to adaptive specializations by inserting into genomic regions around functionally related coding genes. The integration of genomic and transcriptomic analyses indicates independent origins and different components in sea snake and terrestrial snake venom; the venom gland of the sea snake harbours the highest PLA2 (17.23%) expression in selected elapids and these genes may organize tandemly in the genome. These analyses provide insights into the genetic mechanisms that underlay the secondary adaptation to marine and venom production of this sea snake.

scholarly journals Venom Diversity and Evolution in the Most Divergent Cone Snail Genus Profundiconus

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 623 ◽  
Author(s):  
Giulia Fassio ◽  
Maria Vittoria Modica ◽  
Lou Mary ◽  
Paul Zaharias ◽  
Alexander E. Fedosov ◽  
...  
Keyword(s):  
De Novo ◽  
Venom Gland ◽  
Phylogenetic Position ◽  
Cone Snail ◽  
Dietary Breadth ◽  
The Family ◽  
New Gene ◽  
Peptide Toxins ◽  
Transcript Diversity ◽  
Venom Evolution

Profundiconus is the most divergent cone snail genus and its unique phylogenetic position, sister to the rest of the family Conidae, makes it a key taxon for examining venom evolution and diversity. Venom gland and foot transcriptomes of Profundiconus cf. vaubani and Profundiconus neocaledonicus were de novo assembled, annotated, and analyzed for differential expression. One hundred and thirty-seven venom components were identified from P. cf. vaubani and 82 from P. neocaledonicus, with only four shared by both species. The majority of the transcript diversity was composed of putative peptides, including conotoxins, profunditoxins, turripeptides, insulin, and prohormone-4. However, there were also a significant percentage of other putative venom components such as chymotrypsin and L-rhamnose-binding lectin. The large majority of conotoxins appeared to be from new gene superfamilies, three of which are highly different from previously reported venom peptide toxins. Their low conotoxin diversity and the type of insulin found suggested that these species, for which no ecological information are available, have a worm or molluscan diet associated with a narrow dietary breadth. Our results indicate that Profundiconus venom is highly distinct from that of other cone snails, and therefore important for examining venom evolution in the Conidae family.

scholarly journals De Novo Venom-Gland Transcriptomics of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia—Next-Generation Sequencing, Functional Annotation and Toxinological Correlation

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 127
Author(s):  
Choo Hock Tan ◽  
Kae Yi Tan
Keyword(s):  
Next Generation Sequencing ◽  
Amino Acid ◽  
Snake Venom ◽  
De Novo ◽  
Venom Gland ◽  
Individual Species ◽  
Toxin Gene ◽  
Next Generation ◽  
Sea Snake ◽  
Generation Sequencing

Envenomation resulted from sea snake bite is a highly lethal health hazard in Southeast Asia. Although commonly caused by sea snakes of Hydrophiinae, each species is evolutionarily distinct and thus, unveiling the toxin gene diversity within individual species is important. Applying next-generation sequencing, this study investigated the venom-gland transcriptome of Hydrophis curtus (spine-bellied sea snake) from Penang, West Malaysia. The transcriptome was de novo assembled, followed by gene annotation and sequence analyses. Transcripts with toxin annotation were only 96 in number but highly expressed, constituting 48.18% of total FPKM in the overall transcriptome. Of the 21 toxin families, three-finger toxins (3FTX) were the most abundantly expressed and functionally diverse, followed by phospholipases A2. Lh_FTX001 (short neurotoxin) and Lh_FTX013 (long neurotoxin) were the most dominant 3FTXs expressed, consistent with the pathophysiology of envenomation. Lh_FTX001 and Lh_FTX013 were variable in amino acid compositions and predicted epitopes, while Lh_FTX001 showed high sequence similarity with the short neurotoxin from Hydrophis schistosus, supporting cross-neutralization effect of Sea Snake Antivenom. Other toxins of low gene expression, for example, snake venom metalloproteinases and L-amino acid oxidases not commonly studied in sea snake venom were also identified, enriching the knowledgebase of sea snake toxins for future study.

scholarly journals New environment, new invaders - repeated horizontal transfer of LINEs to sea snakes

2020 ◽  
Author(s):  
James D. Galbraith ◽  
Alastair J. Ludington ◽  
Alexander Suh ◽  
Kate L. Sanders ◽  
David L. Adelson
Keyword(s):  
Marine Environment ◽  
Horizontal Transfer ◽  
Marine Invertebrates ◽  
Genomic Sequence ◽  
Marine Species ◽  
Marine Habitat ◽  
Sea Snake ◽  
Sea Snakes ◽  
The One ◽  
Genomic Material

AbstractWhile numerous studies have found horizontal transposon transfer (HTT) to be widespread across metazoans, few have focused on HTT in marine ecosystems. To investigate potential recent HTTs into marine species we searched for novel repetitive elements in sea snakes, a group of elapids which transitioned to a marine habitat at most 18 Mya. Our analysis uncovered repeated HTTs into sea snakes following their marine transition. Such major shifts in habitat should require significant genomic changes.The seven subfamilies of horizontally transferred LINE retrotransposons we identified in the olive sea snake (Aipysurus laevis) are transcribed, and hence are likely still active and expanding across the genome. A search of 600 metazoan genomes found all seven were absent from other amniotes, including terrestrial elapids, with the most similar transposons present in fish and marine invertebrates. The one exception was a similar transposon found in sea kraits, a lineage of amphibious elapids which independently transitioned to a marine environment following their divergence from terrestrial species 25 Mya. Our finding of repeated horizontal transfer events into separate lineages of marine snakes greatly expands past findings of frequent horizontal transfer in the marine environment, suggesting it is ideal for the transfer of transposons.Transposons are drivers of evolution as sources of genomic sequence and hence genomic novelty. This provides evidence of the environment influencing evolution of metazoans not only through specific selection pressures, but also by contributing novel genomic material.

scholarly journals Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

2021 ◽  
Vol 22 (13) ◽  
pp. 7236
Author(s):  
Endah Dwi Hartuti ◽  
Takaya Sakura ◽  
Mohammed S. O. Tagod ◽  
Eri Yoshida ◽  
Xinying Wang ◽  
...  
Keyword(s):  
Drug Target ◽  
De Novo ◽  
Dihydroorotate Dehydrogenase ◽  
Chemical Library ◽  
New Class ◽  
De Novo Biosynthesis ◽  
Starting Point ◽  
Novel Drugs ◽  
Low Toxicity ◽  
Fourth Step

Plasmodium falciparum’s resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.

scholarly journals riboCIRC: a comprehensive database of translatable circRNAs

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huihui Li ◽  
Mingzhe Xie ◽  
Yan Wang ◽  
Ludong Yang ◽  
Zhi Xie ◽  
...  
Keyword(s):  
De Novo ◽  
Species Conservation ◽  
Structure And Function ◽  
Research Community ◽  
Genome Browser ◽  
Valuable Resource ◽  
Sequence Structure ◽  
A Genome ◽  
Context Specific ◽  
And Function

AbstractriboCIRC is a translatome data-oriented circRNA database specifically designed for hosting, exploring, analyzing, and visualizing translatable circRNAs from multi-species. The database provides a comprehensive repository of computationally predicted ribosome-associated circRNAs; a manually curated collection of experimentally verified translated circRNAs; an evaluation of cross-species conservation of translatable circRNAs; a systematic de novo annotation of putative circRNA-encoded peptides, including sequence, structure, and function; and a genome browser to visualize the context-specific occupant footprints of circRNAs. It represents a valuable resource for the circRNA research community and is publicly available at http://www.ribocirc.com.

scholarly journals Venom-gland transcriptomic, venomic, and antivenomic profiles of the spine-bellied sea snake (Hydrophis curtus) from the South China Sea

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hong-Yan Zhao ◽  
Lin Wen ◽  
Yu-Feng Miao ◽  
Yu Du ◽  
Yan Sun ◽  
...  
Keyword(s):  
South China Sea ◽  
South China ◽  
Evolutionary History ◽  
De Novo ◽  
Venom Gland ◽  
The South China Sea ◽  
Protein Families ◽  
The South ◽  
Widespread Species ◽  
China Sea

Abstract Background A comprehensive evaluation of the -omic profiles of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic profiles in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-specific venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes. Results A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-finger toxins (3-FTx), phospholipase A2 (PLA2), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA2 (59.71%/49.36%) were identified as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLA2s. Conclusions Our study clarified the venom-gland transcriptomic and venomic profiles along with the within-group divergence of a H. curtus population from the South China Sea. Adaptive evolution of most venom components driven by natural selection appeared to occur rapidly during evolutionary history. Notably, the utility of commercial N. atra and B. multicinctus antivenoms against H. curtus toxins was not comprehensive; thus, the development of species-specific antivenom is urgently needed.

scholarly journals Structure and function of epididymal protein cysteine-rich secretory protein-1

2007 ◽  
Vol 9 (4) ◽  
pp. 508-514 ◽  
Author(s):  
Kenneth P. Roberts ◽  
Daniel S. Johnston ◽  
Michael A. Nolan ◽  
Joseph L. Wooters ◽  
Nicole C. Waxmonsky ◽  
...  
Keyword(s):  
Secretory Protein ◽  
Structure And Function ◽  
And Function

scholarly journals Pyrobaculum yellowstonensis Strain WP30 Respires on Elemental Sulfur and/or Arsenate in Circumneutral Sulfidic Geothermal Sediments of Yellowstone National Park

2015 ◽  
Vol 81 (17) ◽  
pp. 5907-5916 ◽  
Author(s):  
Z. J. Jay ◽  
J. P. Beam ◽  
A. Dohnalkova ◽  
R. Lohmayer ◽  
B. Bodle ◽  
...  
Keyword(s):  
Yellowstone National Park ◽  
National Park ◽  
Elemental Sulfur ◽  
De Novo ◽  
Hot Spring ◽  
Content Type ◽  
Physiological Attributes ◽  
And Function ◽  
Metagenome Sequence

ABSTRACTThermoproteales(phylumCrenarchaeota) populations are abundant in high-temperature (>70°C) environments of Yellowstone National Park (YNP) and are important in mediating the biogeochemical cycles of sulfur, arsenic, and carbon. The objectives of this study were to determine the specific physiological attributes of the isolatePyrobaculum yellowstonensisstrain WP30, which was obtained from an elemental sulfur sediment (Joseph's Coat Hot Spring [JCHS], 80°C, pH 6.1, 135 μM As) and relate this organism to geochemical processes occurringin situ. Strain WP30 is a chemoorganoheterotroph and requires elemental sulfur and/or arsenate as an electron acceptor. Growth in the presence of elemental sulfur and arsenate resulted in the formation of thioarsenates and polysulfides. The complete genome of this organism was sequenced (1.99 Mb, 58% G+C content), revealing numerous metabolic pathways for the degradation of carbohydrates, amino acids, and lipids. Multiple dimethyl sulfoxide-molybdopterin (DMSO-MPT) oxidoreductase genes, which are implicated in the reduction of sulfur and arsenic, were identified. Pathways for thede novosynthesis of nearly all required cofactors and metabolites were identified. The comparative genomics ofP. yellowstonensisand the assembled metagenome sequence from JCHS showed that this organism is highly related (∼95% average nucleotide sequence identity) toin situpopulations. The physiological attributes and metabolic capabilities ofP. yellowstonensisprovide an important foundation for developing an understanding of the distribution and function of these populations in YNP.

scholarly journals Steroidogenic Factor-1 (SF-1)-Driven Differentiation of Murine Embryonic Stem (ES) Cells into a Gonadal Lineage

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2870-2882 ◽  
Author(s):  
Unmesh Jadhav ◽  
J. Larry Jameson
Keyword(s):  
Target Genes ◽  
De Novo ◽  
Embryoid Body ◽  
Es Cells ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Culture Conditions ◽  
Steroidogenic Factor 1 ◽  
Lineage Differentiation ◽  
And Function

Steroidogenic factor 1 (SF-1) is essential for the development and function of steroidogenic tissues. Stable incorporation of SF-1 into embryonic stem cells (SF-1-ES cells) has been shown to prime the cells for steroidogenesis. When provided with exogenous cholesterol substrate, and after treatment with retinoic acid and cAMP, SF-1-ES cells produce progesterone but do not produce other steroids such as cortisol, estradiol, or testosterone. In this study, we explored culture conditions that optimize SF-1-mediated differentiation of ES cells into defined steroidogenic lineages. When embryoid body formation was used to facilitate cell lineage differentiation, SF-1-ES cells were found to be restricted in their differentiation, with fewer cells entering neuronal pathways and a larger fraction entering the steroidogenic lineage. Among the differentiation protocols tested, leukemia inhibitory factor (LIF) removal, followed by prolonged cAMP treatment was most efficacious for inducing steroidogenesis in SF-1-ES cells. In this protocol, a subset of SF-1-ES cells survives after LIF withdrawal, undergoes morphologic differentiation, and recovers proliferative capacity. These cells are characterized by induction of steroidogenic enzyme genes, use of de novo cholesterol, and production of multiple steroids including estradiol and testosterone. Microarray studies identified additional pathways associated with SF-1 mediated differentiation. Using biotinylated SF-1 in chromatin immunoprecipitation assays, SF-1 was shown to bind directly to multiple target genes, with induction of binding to some targets after steroidogenic treatment. These studies indicate that SF-1 expression, followed by LIF removal and treatment with cAMP drives ES cells into a steroidogenic pathway characteristic of gonadal steroid-producing cells.

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