Abstract

BackgroundVenom variation occurs at all taxonomical levels and can impact significantly upon the clinical manifestations and efficacy of antivenom therapy following snakebite. Variation in snake venom composition is thought to be subject to strong natural selection as a result of adaptation towards specific diets. Members of the medically important genus Echis exhibit considerable variation in venom composition, which has been demonstrated to co-evolve with evolutionary shifts in diet. We adopt a venom gland transcriptome approach in order to investigate the diversity of toxins in the genus and elucidate the mechanisms which result in prey-specific adaptations of venom composition.ResultsVenom gland transcriptomes were created for E. pyramidum leakeyi, E. coloratus and E. carinatus sochureki by sequencing ~1000 expressed sequence tags from venom gland cDNA libraries. A standardised methodology allowed a comprehensive intra-genus comparison of the venom gland profiles to be undertaken, including the previously described E. ocellatus transcriptome. Blast annotation revealed the presence of snake venom metalloproteinases, C-type lectins, group II phopholipases A2, serine proteases, L-amino oxidases and growth factors in all transcriptomes throughout the genus. Transcripts encoding disintegrins, cysteine-rich secretory proteins and hyaluronidases were obtained from at least one, but not all, species. A representative group of novel venom transcripts exhibiting similarity to lysosomal acid lipase were identified from the E. coloratus transcriptome, whilst novel metallopeptidases exhibiting similarity to neprilysin and dipeptidyl peptidase III were identified from E. p. leakeyi and E. coloratus respectively.ConclusionThe comparison of Echis venom gland transcriptomes revealed substantial intrageneric venom variation in representations and cluster numbers of the most abundant venom toxin families. The expression profiles of established toxin groups exhibit little obvious association with venom-related adaptations to diet described from this genus. We suggest therefore that alterations in isoform diversity or transcript expression levels within the major venom protein families are likely to be responsible for prey specificity, rather than differences in the representation of entire toxin families or the recruitment of novel toxin families, although the recruitment of lysosomal acid lipase as a response to vertebrate feeding cannot be excluded. Evidence of marked intrageneric venom variation within the medically important genus Echis strongly advocates further investigations into the medical significance of venom variation in this genus and its impact upon antivenom therapy.

Highlights

  • Venom variation occurs at all taxonomical levels and can impact significantly upon the clinical manifestations and efficacy of antivenom therapy following snakebite

  • We demonstrated that the four species complexes making up this genus, the E. carinatus, E. ocellatus, E. pyramidum and E. coloratus species groups [10,25], exhibit considerable vertebrate or invertebrate dietary preferences, E. coloratus being a vertebrate specialist whereas invertebrates feature prominently in the diet of the others

  • Each individual venom transcript cannot be correlated with the mature venom proteome without considerable extra experimental verification, our own work with E. ocellatus [28] shows there is a good general accordance between the venom proteome and that predicted from the venom gland transcriptome

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Summary

Introduction

Venom variation occurs at all taxonomical levels and can impact significantly upon the clinical manifestations and efficacy of antivenom therapy following snakebite. Variation in snake venom composition is thought to be subject to strong natural selection as a result of adaptation towards specific diets. The view that variation in venom composition evolves primarily through neutral evolutionary processes [4,5,6] is not supported by other reports that snake venom composition is subject to strong natural selection as a result of adaptation towards specific diets [e.g. Irrespective of the evolutionary forces underpinning venom protein composition, variation in venom components can significantly impact upon the clinical manifestations of snake envenoming [13,14,15] and, because the clinical efficacy of an antivenom may be largely restricted to the venom used in its manufacture, the success of antivenom therapy [16,17,18]. A preliminary venom protein analysis using reduced SDS-PAGE failed to identify an obvious link between venom composition and diet [10], justifying the use of a more comprehensive venom composition analysis in order to elucidate the mechanisms driving venom adaptations within the Echis viper genus

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