Original Publication Date
BMC Molecular Biology 2007
DOI of Original Publication
Date of Submission
Snake venoms are complex mixtures of pharmacologically active proteins and peptides which belong to a small number of superfamilies. Global cataloguing of the venom transcriptome facilitates the identification of new families of toxins as well as helps in understanding the evolution of venom proteomes.
We have constructed a cDNA library of the venom gland of a threatened rattlesnake (a pitviper),Sistrurus catenatus edwardsii (Desert Massasauga), and sequenced 576 ESTs. Our results demonstrate a high abundance of serine proteinase and metalloproteinase transcripts, indicating that the disruption of hemostasis is a principle mechanism of action of the venom. In addition to the transcripts encoding common venom proteins, we detected two varieties of low abundance unique transcripts in the library; these encode for three-finger toxins and a novel toxin possibly generated from the fusion of two genes. We also observed polyadenylated ribosomal RNAs in the venom gland library, an interesting preliminary obsevation of this unusual phenomenon in a reptilian system.
The three-finger toxins are characteristic of most elapid venoms but are rare in viperid venoms. We detected several ESTs encoding this group of toxins in this study. We also observed the presence of a transcript encoding a fused protein of two well-characterized toxins (Kunitz/BPTI and Waprins), and this is the first report of this kind of fusion in a snake toxin transcriptome. We propose that these new venom proteins may have ancillary functions for envenomation. The presence of a fused toxin indicates that in addition to gene duplication and accelerated evolution, exon shuffling or transcriptional splicing may also contribute to generating the diversity of toxins and toxin isoforms observed among snake venoms. The detection of low abundance toxins, as observed in this and other studies, indicates a greater compositional similarity of venoms (though potency will differ) among advanced snakes than has been previously recognized.
© 2007 Pahari et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Is Part Of
VCU Biochemistry and Molecular Biology Publications
It is a table showing the distribution of snake venom toxin families among Superfamily Colubroidae.
1471-2199-8-115-s2.pdf (34 kB)
It is a table showing the clusters of ESTs, number of clones in each cluster and their putative identity.
1471-2199-8-115-s3.pdf (36 kB)
It is a table showing the clusters of ESTs encoding cellular proteins.
1471-2199-8-115-s4.pdf (5 kB)
ClustalW alignment between 12S ribosomal RNA sequence DQ464268 (from this study) and AF057227 (used for taxonomic identification of S. c. edwardsii). Polyadenylation signal sequence is underlined.
1471-2199-8-115-s5.pdf (25 kB)
ClustalW alignment of PIII metalloproteinases (only proteinase domain is shown). Cysteine residues which are conserved are marked in grey and variable in black. Accession numbers of the used sequences are as follows: VAP1 [GenBank: BAB18307], HV1 [GenBank: BAB60682], Halysase [GenBank: 27465044], VLAIP-A [GenBank: 61104775], VLAIP-B [GenBank: 61104777], Kaouthiagin [Swiss-Prot: P82942], Berythractivase [Swiss-Prot: Q8UVG0], Ecarin [Swiss-Prot: Q90495], Jararhagin [Swiss-Prot: P30431], Bothropasin [Swiss-Prot: O93523], Acurhagin [Swiss-Prot: Q6Q274], Catrocollastatin [Swiss-Prot: Q90282], Atrolysin [Swiss-Prot: Q92043], Stejnihagin-A [Swiss-Prot: Q3HTN1], Stejnihagin-B [Swiss-Prot: Q3HTN2], HR1A [Swiss-Prot: Q8JIR2], HR1B [Swiss-Prot: P20164], HF3 [GenBank: 31742525]. P, signal peptide domain; PRO, pro-domain; S, spacer; DISIN, disintegrin domain; CRD, cysteine-rich domain
1471-2199-8-115-s6.pdf (24 kB)
Bayesian tree generated from 39 aligned 3FTx sequences as described in Materials and Methods. Numbers on branches indicate percentage of posterior clade probability. 3FTx sequences from S. c. edwardsii and L. muta libraries are marked with a filled circle and triangle respectively.