Abstract
Background The identification of apparently conserved gene complements in the venom and salivary glands of a diverse set of reptiles led to the development of the Toxicofera hypothesis – the idea that there was a single, early evolution of the venom system in reptiles. However, this hypothesis is based largely on relatively small scale EST-based studies of only venom or salivary glands and toxic effects have been assigned to only some of these putative Toxcoferan toxins in some species. We set out to investigate the distribution of these putative venom toxin transcripts in order to investigate to what extent conservation of gene complements may reflect a bias in previous sampling efforts.
Results We have carried out the first large-scale test of the Toxicofera hypothesis and found it lacking in a number of regards. Our quantitative transcriptomic analyses of venom and salivary glands and other body tissues in five species of reptile, together with the use of available RNA-Seq datasets for additional species shows that the majority of genes used to support the establishment and expansion of the Toxicofera are in fact expressed in multiple body tissues and most likely represent general maintenance or “housekeeping” genes. The apparent conservation of gene complements across the Toxicofera therefore reflects an artefact of incomplete tissue sampling. In other cases, the identification of a non-toxic paralog of a gene encoding a true venom toxin has led to confusion about the phylogenetic distribution of that venom component.
Conclusions Venom has evolved multiple times in reptiles. In addition, the misunderstanding regarding what constitutes a toxic venom component, together with the misidentification of genes and the classification of identical or near-identical sequences as distinct genes has led to an overestimation of the complexity of reptile venoms in general, and snake venom in particular, with implications for our understanding of (and development of treatments to counter) the molecules responsible for the physiological consequences of snakebite.
