Vexitoxins: a novel class of conotoxin-like venom peptides from predatory gastropods of the genus Vexillum

Venoms of predatory marine cone snails (the family Conidae, order Neogastropoda) are intensely studied because of the broad range of biomedical applications of the neuropeptides that they contain, conotoxins. Meanwhile anatomy in some other neogastropod lineages strongly suggests that they have evolved similar venoms independently of cone snails, nevertheless their venom composition remains unstudied. Here we focus on the most diversified of these lineages, the genus Vexillum (the family Costellariidae). We have generated comprehensive multi-specimen, multi-tissue RNA-Seq data sets for three Vexillum species, and supported our findings in two species by proteomic profiling. We show that venoms of Vexillum are dominated by highly diversified short cysteine-rich peptides that in many aspects are very similar to conotoxins. Vexitoxins possess the same precursor organization, display overlapping cysteine frameworks and share several common post-translational modifications with conotoxins. Some vexitoxins show detectable sequence similarity to conotoxins, and are predicted to adopt similar domain conformations, including a pharmacologically relevant inhibitory cysteine-know motif (ICK). The tubular gL of Vexillum is a notably more recent evolutionary novelty than the conoidean venom gland. Thus, we hypothesize lower divergence between the toxin genes, and their somatic counterparts compared to that in conotoxins, and we find support for this hypothesis in the molecular evolution of the vexitoxin cluster V027. We use this example to discuss how future studies on vexitoxins can inform origin and evolution of conotoxins, and how they may help addressing standing questions in venom evolution.

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

Toxins ◽

10.3390/toxins11110623 ◽

2019 ◽

Vol 11 (11) ◽

pp. 623 ◽

Cited By ~ 2

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.

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Proteomics and Deep Sequencing Comparison of Seasonally Active Venom Glands in the Platypus Reveals Novel Venom Peptides and Distinct Expression Profiles

Molecular & Cellular Proteomics ◽

10.1074/mcp.m112.017491 ◽

2012 ◽

Vol 11 (11) ◽

pp. 1354-1364 ◽

Cited By ~ 30

Author(s):

Emily S. W. Wong ◽

David Morgenstern ◽

Ehtesham Mofiz ◽

Sara Gombert ◽

Katrina M. Morris ◽

...

Keyword(s):

Breeding Season ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Venom Gland ◽

Rna Seq ◽

Growth Differentiation Factor 15 ◽

Stress Response Pathway ◽

Venom Glands ◽

Venom Evolution ◽

Venom Proteins

The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution.

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Bacterial genome chimaerism and the origin of mitochondria

Canadian Journal of Microbiology ◽

10.1139/w10-099 ◽

2011 ◽

Vol 57 (1) ◽

pp. 49-61 ◽

Cited By ~ 23

Author(s):

Ankur Abhishek ◽

Anish Bavishi ◽

Ashay Bavishi ◽

Madhusudan Choudhary

Keyword(s):

Rhodospirillum Rubrum ◽

Sequence Similarity ◽

Phylogenetic Analyses ◽

Bacterial Genome ◽

Sister Group ◽

Rickettsia Prowazekii ◽

Origin And Evolution ◽

The Family ◽

Related Proteins ◽

Similarity Searches

Many studies have sought to determine the origin and evolution of mitochondria. Although the Alphaproteobacteria are thought to be the closest relatives of the mitochondrial progenitor, there is dispute as to what its particular sister group is. Some have argued that mitochondria originated from ancestors of the order Rickettsiales, or more specifically of the Rickettsiaceae family, while others believe that ancestors of the family Rhodospirillaceae are also equally likely the progenitors. To resolve some of these disputes, sequence similarity searches and phylogenetic analyses were performed against mitochondria-related proteins in Saccharomyces cerevisiae . The 86 common matches of 5 Alphaproteobacteria ( Rickettsia prowazekii , Rhodospirillum rubrum , R hodopseudomonas palustris , Rhodobacter sphaeroides , and Ochrobactrum anthropi ) to yeast mitochondrial proteins were distributed fairly evenly among the 5 species when sorted by highest identity or score. Moreover, exploratory phylogenetic analyses revealed that among these common matches, 44.19% (38) had branched most closely with O. anthropi, while only 34.88% (30) corresponded with Rickettsia prowazekii. More detailed phylogenetic analyses with additional Alphaproteobacteria and including genes from the mitochondria of Reclinomonas americana found matches of mitochondrial genes to those of members of the Rickettsiaceae, Anaplasmataceae, and Rhodospirillaceae families. The results support the idea that notable bacterial genome chimaerism has occurred en route to the formation of mitochondria.

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Sequence diversity and evolution of a group of iflaviruses associated with ticks

Archives of Virology ◽

10.1007/s00705-021-05060-8 ◽

2021 ◽

Author(s):

Romain Daveu ◽

Caroline Hervet ◽

Louane Sigrist ◽

Davide Sassera ◽

Aaron Jex ◽

...

Keyword(s):

Cell Line ◽

Evolutionary Dynamics ◽

Ixodes Scapularis ◽

Data Sets ◽

Virus Species ◽

Rna Seq ◽

Genome Sequences ◽

Synonymous Mutations ◽

The Family ◽

Insight Into

AbstractWe studied a group of tick-associated viruses with characteristics of members of the family Iflaviridae, a family of viruses frequently found in arthropods. Our aim was to gain insight into the evolutionary dynamics of this group of viruses, which may be linked to the biology of ticks. We explored assembled RNA-Seq data sets for different species of ticks. We identified members of five different iflavirus species, four of them novel, and discovered nine new genome sequences, including variants. Five variants represented a virus species associated with Ixodes ricinus. Unexpectedly, a sequence found in the Ixodes scapularis cell line ISE6 was nearly identical to the sequences of I. ricinus variants, suggesting a contamination of this cell line by I. ricinus material. Analysing patterns of substitutions between these variants, we detected a strong excess of synonymous mutations, suggesting evolution under strong positive selection. The phylogenies of the viruses and of their tick hosts were not congruent, suggesting recurrent host changes across tick genera during their evolution. Overall, our work constitutes a step in the understanding of the interactions between this family of viruses and ticks.

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Monoglobus pectinilyticus gen. nov., sp. nov., a pectinolytic bacterium isolated from human faeces.

10.26686/wgtn.12597812.v1 ◽

2020 ◽

Author(s):

CC Kim ◽

WJ Kelly ◽

ML Patchett ◽

GW Tannock ◽

Z Jordens ◽

...

Keyword(s):

16S Rrna ◽

16S Rrna Gene ◽

Sequence Similarity ◽

Middle Lamella ◽

Rrna Gene ◽

Gene Sequences ◽

16S Rrna Gene Sequences ◽

Citrus Peel ◽

Human Faeces ◽

The Family

© 2017 IUMS. A novel anaerobic pectinolytic bacterium (strain 14T) was isolated from human faeces. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 14T belonged to the family Ruminococcaceae, but was located separately from known clostridial clusters within the taxon. The closest cultured relative of strain 14T was Acetivibrio cellulolyticus (89.7% sequence similarity). Strain 14T shared ~99% sequence similarity with cloned 16S rRNA gene sequences from uncultured bacteria derived from the human gut. Cells were Gram-stain-positive, non-motile cocci approximately 0.6μm in diameter. Strain 14T fermented pectins from citrus peel, apple, and kiwifruit as well as carbohydrates that are constituents of pectins and hemicellulose, such as galacturonic acid, xylose, and arabinose. TEM images of strain 14T, cultured in association with plant tissues, suggested extracellular fibrolytic activity associated with the bacterial cells, forming zones of degradation in the pectin-rich regions of middle lamella. Phylogenetic and phenotypic analysis supported the differentiation of strain 14T as a novel genus in the family Ruminococcaceae. The name Monoglobus pectinilyticus gen. nov., sp. nov. is proposed; the type strain is 14T (JCM 31914T=DSM 104782T).

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Discriminating between JCPyV and BKPyV in Urinary Virome Data Sets

Viruses ◽

10.3390/v13061041 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1041

Author(s):

Rita Mormando ◽

Alan J. Wolfe ◽

Catherine Putonti

Keyword(s):

Jc Virus ◽

Sequence Similarity ◽

Bk Virus ◽

Data Sets ◽

Metagenomic Sequencing ◽

Significant Sequence Similarity ◽

Sequence Identity ◽

Shotgun Metagenomic Sequencing ◽

Urinary Microbiome ◽

Six Genes

Polyomaviruses are abundant in the human body. The polyomaviruses JC virus (JCPyV) and BK virus (BKPyV) are common viruses in the human urinary tract. Prior studies have estimated that JCPyV infects between 20 and 80% of adults and that BKPyV infects between 65 and 90% of individuals by age 10. However, these two viruses encode for the same six genes and share 75% nucleotide sequence identity across their genomes. While prior urinary virome studies have repeatedly reported the presence of JCPyV, we were interested in seeing how JCPyV prevalence compares to BKPyV. We retrieved all publicly available shotgun metagenomic sequencing reads from urinary microbiome and virome studies (n = 165). While one third of the data sets produced hits to JCPyV, upon further investigation were we able to determine that the majority of these were in fact BKPyV. This distinction was made by specifically mining for JCPyV and BKPyV and considering uniform coverage across the genome. This approach provides confidence in taxon calls, even between closely related viruses with significant sequence similarity.

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Development of genic KASP SNP markers from RNA-Seq data for map-based cloning and marker-assisted selection in maize

BMC Plant Biology ◽

10.1186/s12870-021-02932-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhengjie Chen ◽

Dengguo Tang ◽

Jixing Ni ◽

Peng Li ◽

Le Wang ◽

...

Keyword(s):

Marker Assisted Selection ◽

Inbred Lines ◽

Average Density ◽

Snp Markers ◽

Data Sets ◽

Rna Seq ◽

Specific Pcr ◽

Maize Inbred Lines ◽

Allele Specific ◽

Allele Specific Pcr

Abstract Background Maize is one of the most important field crops in the world. Most of the key agronomic traits, including yield traits and plant architecture traits, are quantitative. Fine mapping of genes/ quantitative trait loci (QTL) influencing a key trait is essential for marker-assisted selection (MAS) in maize breeding. However, the SNP markers with high density and high polymorphism are lacking, especially kompetitive allele specific PCR (KASP) SNP markers that can be used for automatic genotyping. To date, a large volume of sequencing data has been produced by the next generation sequencing technology, which provides a good pool of SNP loci for development of SNP markers. In this study, we carried out a multi-step screening method to identify kompetitive allele specific PCR (KASP) SNP markers based on the RNA-Seq data sets of 368 maize inbred lines. Results A total of 2,948,985 SNPs were identified in the high-throughput RNA-Seq data sets with the average density of 1.4 SNP/kb. Of these, 71,311 KASP SNP markers (the average density of 34 KASP SNP/Mb) were developed based on the strict criteria: unique genomic region, bi-allelic, polymorphism information content (PIC) value ≥0.4, and conserved primer sequences, and were mapped on 16,161 genes. These 16,161 genes were annotated to 52 gene ontology (GO) terms, including most of primary and secondary metabolic pathways. Subsequently, the 50 KASP SNP markers with the PIC values ranging from 0.14 to 0.5 in 368 RNA-Seq data sets and with polymorphism between the maize inbred lines 1212 and B73 in in silico analysis were selected to experimentally validate the accuracy and polymorphism of SNPs, resulted in 46 SNPs (92.00%) showed polymorphism between the maize inbred lines 1212 and B73. Moreover, these 46 polymorphic SNPs were utilized to genotype the other 20 maize inbred lines, with all 46 SNPs showing polymorphism in the 20 maize inbred lines, and the PIC value of each SNP was 0.11 to 0.50 with an average of 0.35. The results suggested that the KASP SNP markers developed in this study were accurate and polymorphic. Conclusions These high-density polymorphic KASP SNP markers will be a valuable resource for map-based cloning of QTL/genes and marker-assisted selection in maize. Furthermore, the method used to develop SNP markers in maize can also be applied in other species.

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A new non-aggregative splicing isoform of human Tau is decreased in Alzheimer’s disease

Acta Neuropathologica ◽

10.1007/s00401-021-02317-z ◽

2021 ◽

Author(s):

Vega García-Escudero ◽

Daniel Ruiz-Gabarre ◽

Ricardo Gargini ◽

Mar Pérez ◽

Esther García ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neuroblastoma Cells ◽

Rna Seq ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Post Translational Modifications ◽

Protein Levels ◽

Tau Isoform ◽

Human Specific

AbstractTauopathies, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration with Tau pathology (FTLD-tau), are a group of neurodegenerative disorders characterized by Tau hyperphosphorylation. Post-translational modifications of Tau such as phosphorylation and truncation have been demonstrated to be an essential step in the molecular pathogenesis of these tauopathies. In this work, we demonstrate the existence of a new, human-specific truncated form of Tau generated by intron 12 retention in human neuroblastoma cells and, to a higher extent, in human RNA brain samples, using qPCR and further confirming the results on a larger database of human RNA-seq samples. Diminished protein levels of this new Tau isoform are found by Westernblotting in Alzheimer’s patients’ brains (Braak I n = 3; Braak II n = 6, Braak III n = 3, Braak IV n = 1, and Braak V n = 10, Braak VI n = 8) with respect to non-demented control subjects (n = 9), suggesting that the lack of this truncated isoform may play an important role in the pathology. This new Tau isoform exhibits similar post-transcriptional modifications by phosphorylation and affinity for microtubule binding, but more interestingly, is less prone to aggregate than other Tau isoforms. Finally, we present evidence suggesting this new Tau isoform could be linked to the inhibition of GSK3β, which would mediate intron 12 retention by modulating the serine/arginine rich splicing factor 2 (SRSF2). Our results show the existence of an important new isoform of Tau and suggest that further research on this less aggregation-prone Tau may help to develop future therapies for Alzheimer’s disease and other tauopathies.

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MUREN: a robust and multi-reference approach of RNA-seq transcript normalization

BMC Bioinformatics ◽

10.1186/s12859-021-04288-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yance Feng ◽

Lei M. Li

Keyword(s):

Biological Significance ◽

Housekeeping Genes ◽

R Package ◽

Data Sets ◽

Statistical Regression ◽

Rna Seq ◽

Least Trimmed Squares ◽

Standard Data ◽

Wide Range ◽

Multiple References

Abstract Background Normalization of RNA-seq data aims at identifying biological expression differentiation between samples by removing the effects of unwanted confounding factors. Explicitly or implicitly, the justification of normalization requires a set of housekeeping genes. However, the existence of housekeeping genes common for a very large collection of samples, especially under a wide range of conditions, is questionable. Results We propose to carry out pairwise normalization with respect to multiple references, selected from representative samples. Then the pairwise intermediates are integrated based on a linear model that adjusts the reference effects. Motivated by the notion of housekeeping genes and their statistical counterparts, we adopt the robust least trimmed squares regression in pairwise normalization. The proposed method (MUREN) is compared with other existing tools on some standard data sets. The goodness of normalization emphasizes on preserving possible asymmetric differentiation, whose biological significance is exemplified by a single cell data of cell cycle. MUREN is implemented as an R package. The code under license GPL-3 is available on the github platform: github.com/hippo-yf/MUREN and on the conda platform: anaconda.org/hippo-yf/r-muren. Conclusions MUREN performs the RNA-seq normalization using a two-step statistical regression induced from a general principle. We propose that the densities of pairwise differentiations are used to evaluate the goodness of normalization. MUREN adjusts the mode of differentiation toward zero while preserving the skewness due to biological asymmetric differentiation. Moreover, by robustly integrating pre-normalized counts with respect to multiple references, MUREN is immune to individual outlier samples.

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Molecular diversity and evolutionary trends of cysteine-rich peptides from the venom glands of Chinese spider Heteropoda venatoria

Scientific Reports ◽

10.1038/s41598-021-82668-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jie Luo ◽

Yiying Ding ◽

Zhihao Peng ◽

Kezhi Chen ◽

Xuewen Zhang ◽

...

Keyword(s):

Expressed Sequence Tags ◽

Molecular Diversity ◽

Insect Pests ◽

Phylogenetic Analyses ◽

Spider Venom ◽

Evolutionary Trends ◽

The Family ◽

Venom Glands ◽

Venom Evolution ◽

Expressed Sequence

AbstractHeteropoda venatoria in the family Sparassidae is highly valued in pantropical countries because the species feed on domestic insect pests. Unlike most other species of Araneomorphae, H. venatoria uses the great speed and strong chelicerae (mouthparts) with toxin glands to capture the insects instead of its web. Therefore, H. venatoria provides unique opportunities for venom evolution research. The venom of H. venatoria was explored by matrix-assisted laser desorption/ionization tandem time-of-flight and analyzing expressed sequence tags. The 154 sequences coding cysteine-rich peptides (CRPs) revealed 24 families based on the phylogenetic analyses of precursors and cysteine frameworks in the putative mature regions. Intriguingly, four kinds of motifs are first described in spider venom. Furthermore, combining the diverse CRPs of H. venatoria with previous spider venom peptidomics data, the structures of precursors and the patterns of cysteine frameworks were analyzed. This work revealed the dynamic evolutionary trends of venom CRPs in H. venatoria: the precursor has evolved an extended mature peptide with more cysteines, and a diminished or even vanished propeptides between the signal and mature peptides; and the CRPs evolved by multiple duplications of an ancestral ICK gene as well as recruitments of non-toxin genes.

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