Accelerated Evolution of Fetuin Family Proteins in<i>Protobothrops flavoviridis</i>(Habu Snake) Serum and the Discovery of an L1-Like Genomic Element in the Intronic Sequence of a Fetuin-Encoding Gene

Tanaka, Yasuyoshi; Oyama, Sachiko; Hori, Shingo; Ushio, Koya; Shioi, Narumi; Terada, Shigeyuki; Deshimaru, Masanobu

doi:10.1271/bbb.120829

Cited by 7 publications

(5 citation statements)

References 61 publications

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“…In fact, TRL1L occurs in a small number of copies, most of which are likely to be represented by truncated insertions of full‐length L1 elements. This hypothesis is also supported by the partial amino acid identity of TRL1L forced translation with the transposase gene of a full‐length L1 element of P. flavoviridis (Tanaka et al ., ) (see Fig. c).…”

Section: Discussionmentioning

confidence: 99%

“…In snakes, the genomic localization of different L1 elements is highly variable, ranging from coding to repetitive regions. In P. flavoviridis, a full‐length L1 has been found in the intronic region of the Habu serum‐like (HBL) protein, a member of the fetuin family, (Tanaka et al ., ), while a truncated sequence showing about 60% identity with TRL1L sequences is present in a microsatellite region of Agkistrodon contortrix (Linnaeus, 1766) (GenBank A.N. ) (Castoe et al ., ).…”

Section: Discussionmentioning

confidence: 99%

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Non‐random accumulation of LINE1‐like sequences on differentiated snake W chromosomes

et al. 2016

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Abstract\ud Due to their particular phylogenetic position and biological characteristics, squamate\ud reptiles and, in particular, snakes are becoming an increasingly important\ud model for fields such as evolutionary biology, molecular ecology and adaptation.\ud Recently, during a study to analyze the evolutionary history of European whip\ud snakes, we found a LINE1 (L1)-like sequence (GenBank accession no.\ud LM644476), herein called TRL1L, and while there are data on the abundance of\ud L1 in snakes, their genomic and chromosome localization is still largely unexplored.\ud We therefore performed a study to obtain information on TRL1L abundance,\ud distribution and conservation in snake species, belonging to the Colubridae,\ud Lamprophiidae and Viperidae families, using quantitative dot-blot and fluorescence\ud in situ hybridization (FISH). TRL1L showed a high identity with homologous\ud segments of L1s of lizards the Anolis carolinensis and Lacerta agilis and the zebrafish\ud Danio rerio. The discovered sequences are truncated L1 elements which\ud occur with a low copy number, about 0.1% of the genome of the species studied.\ud This evidence suggests that L1 retroposons have a similar landscape in lizard and\ud snake genomes, probably because similar processes limited L1 distribution in their\ud genomes. TRL1L showed a non-random chromosome distribution pattern. It\ud was scarcely located on autosomes and on the euchromatic W chromosome of\ud Cerastes vipera, while mostly found on the heterochromatic W chromosome of\ud Hierophis carbonarius and Elaphe quatuorlineata. Our data support the hypothesis\ud that a ‘purifying selection’ against the accumulation of L1 elements takes place in\ud recombining regions and highlight the possible role of these elements in the differentiation\ud processes of the snake heterochromatic W chromosome. Interestingly, the\ud preferential distribution of TRL1L on the heterochromatic W chromosomes of the\ud studied snakes appears to be similar to that observed in mammals for L1 accumulation\ud on differentiated Y chromosomes. This finding suggests that a convergent\ud process may have taken place in the differentiation of vertebrate heterochromatic\ud sex chromosome

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Non‐random accumulation of LINE1‐like sequences on differentiated snake W chromosomes

et al. 2016

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“…This is in agreement with the molecular evolution of SSP genes, where the number of non-synonymous nucleotide substitutions is significantly greater than those of synonymous substitutions in N-terminal regions. Additionally, these mutational hotspots are found on the molecular surface, specifically located on the toxin interaction interface, while the protein scaffold structure is highly conserved [62].…”

Section: Small Serum Proteins (Ssps)mentioning

confidence: 99%

“…Endogenous inhibitor genes are expressed in the liver of venomous snakes, and these genes appear to be evolving by gene duplication and rapid diversification. This facilitates the neutralization of various toxins within venoms, which also are evolving under similar mechanism [62,72]. Thus, a detailed characterization of inhibitors against species-specific toxins may help to decipher the evolution of endogenous natural resistance in venomous snakes.…”

Section: Undetermined Proteinous Inhibitorsmentioning

confidence: 99%

Snakebite Therapeutics Based on Endogenous Inhibitors from Vipers

Aoki-Shioi¹,

Modahl²

2021

Medical Toxicology

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Venomous snakebite is a major human health issue in many countries and has been categorized as a neglected tropical disease by the World Health Organization. Venomous snakes have evolved to produce venom, which is a complex mixture of toxic proteins and peptides, both enzymatic and nonenzymatic in nature. In this current era of high-throughput technologies, venomics projects, which include genome, transcriptome, and proteome analyses of various venomous species, have been conducted to characterize divergent venom phenotypes and the evolution of venom-related genes. Additionally, venomics can also inform about mechanisms of toxin production, storage, and delivery. Venomics can guide antivenom and therapeutic strategies against envenomations and identify new toxin-derived drugs/tools. One potentially promising drug development direction is the use of endogenous inhibitors present in snake venom glands and serum that could be useful for snakebite therapeutics. These inhibitors suppress the activity of venom proteases, enzymatic proteins responsible for the irreversible damage from snakebite. This book chapter will focus on insights from venomous snake adaptations, such as the evolution of venom proteases to generate diverse activities and snake natural resistance to inhibit activity, and how this information can inform and have applications in the treatment of venomous snakebite.

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“…Moreover, the habu snake liver RNA indicated active transcription of the PfRT. This suggests that sufficient RT activity could contribute to the accelerated evolution of exonic nucleotide sequences in the genes for venom proteins (154). Likewise, SINE in SVMPs transcripts may play a role in generation of SVMPs gene diversity.…”

Section: Retrotransposable Sequences (Sines)mentioning

confidence: 99%

Characterisation of Metalloproteinases from Myanmar Russell's Viper

Than Yee

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Russell’s viper bites are a major public health problem in tropical and subtropical regions. In Myanmar, a Russell’s viper (Daboia russellii siamensis) bite has a 60% morbidity rate and 8.2% fatality rate. Most victims encounter severe bleeding, renal failure and capillary leakage and the bite can possibly lead to death. Snake venom metalloproteinases (SVMPs) are the major components of the Viperidae venom and all mentioned lethal effects of the bites are attributed to these. The only available and partially effective agent for the treatment of the toxic effects is antivenom. Antivenom therapy is not always effective towards small toxins, however, and it can also provoke an anaphylactic response. The development of new therapeutic approaches is becoming increasingly important therefore. For the analysis of SVMP transcripts from Myanmar Russell’s viper, Next-Generation Sequencing (NGS) of mRNA from venom glands derived from 2 male snakes and 1 female snake was performed on an Illumina HiSeq2000 platform. De novo assembly of the reads was performed using Trinity software and the transcripts were annotated through Blastn against the collection of NCBI nucleotide sequences defined by a key-word (‘venom’ and ‘serpents’) search. Blastx hit results against the UniProtKB/Swiss-Prot (swissprot) database were also used for annotation of the transcripts. The abundance distribution (in term of FPKM value) of SVMPs toxin transcripts: disintegrin (75%), P-III SVMPs (25%) and P-II SVMPs (0.002 %), were the same for both male and female samples. P-III SVMPs were found to be expressed at a higher level than P-II in MRV venom glands for both sex groups. No P-I SVMP transcripts was detected in the present analysis. A comparison of the contents of SVMP transcripts in adult male and female venom glands showed some gender-related differences. A disintegrin transcript isoform (Dis 1b) was highly expressed only in the female venom gland. Some P-III SVMP isoforms (P-III 6, 7a, 7b) were only expressed in the male venom glands at low expression levels. The P-II SVMP transcripts expressed as different isoforms in male and female. This could reflect a sex-dimorphism of viper venom biological activities. This finding would support a requirement to use combined venoms of both sexes for preparation of antivenom. In addition to SVMP transcripts, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs) were also discovered. These endogenous inhibitors have potentials as a new treatment modality for neutralization of the effect of SVMP toxins. Two major snake SVMPs, RVV-X and Daborhagin, were purified from Myanmar Russell’s viper venom using a new purification strategy. Moreover, the two novel endogenous tripeptides identified in transcript analysis, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, synthetic versions of the peptide inhibitors, pERW and pEKW, completely inhibited the gelatinolytic and fibrinogenolytic activities of the respective SVMPs when used at 5 mM (estimated molar ratio of SVMP to tripeptide was 1:500). These complete inhibitory effects suggest that these tripeptides deserve further study as candidates for new therapeutic treatment against Russell’s viper envenomation.

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Accelerated Evolution of Fetuin Family Proteins inProtobothrops flavoviridis(Habu Snake) Serum and the Discovery of an L1-Like Genomic Element in the Intronic Sequence of a Fetuin-Encoding Gene

Cited by 7 publications

References 61 publications

Non‐random accumulation of LINE1‐like sequences on differentiated snake W chromosomes

Non‐random accumulation of LINE1‐like sequences on differentiated snake W chromosomes

Snakebite Therapeutics Based on Endogenous Inhibitors from Vipers

Characterisation of Metalloproteinases from Myanmar Russell's Viper

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