Lachesis muta (Viperidae) cDNAs Reveal Diverging Pit Viper Molecules and Scaffolds Typical of Cobra (Elapidae) Venoms: Implications for Snake Toxin Repertoire Evolution

Abstract

Efforts to describe toxins from the two major families of venomous snakes (Viperidae and Elapidae) usually reveal proteins belonging to few structural types, particular of each family. Here we carried on an effort to determine uncommon cDNAs that represent possible new toxins from Lachesis muta (Viperidae). In addition to nine classes of typical toxins, atypical molecules never observed in the hundreds of Viperidae snakes studied so far are highly expressed: a diverging C-type lectin that is related to Viperidae toxins but appears to be independently originated; an ohanin-like toxin, which would be the third member of the most recently described class of Elapidae toxins, related to human butyrophilin and B30.2 proteins; and a 3FTx-like toxin, a new member of the widely studied three-finger family of proteins, which includes major Elapidae neurotoxins and CD59 antigen. The presence of these common and uncommon molecules suggests that the repertoire of toxins could be more conserved between families than has been considered, and their features indicate a dynamic process of venom evolution through molecular mechanisms, such as multiple recruitments of important scaffolds and domain exchange between paralogs, always keeping a minimalist nature in most toxin structures in opposition to their nontoxin counterparts.

Snake venomics of the South and Central American Bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis

“…Comparison of the protein composition of the venom of L. muta determined using a proteomic (this work) and a transcriptomic approach [23] shows clear differences, both in the relative occurrence of protein families (expressed as percentages of the total HPLC-separated proteins) (Fig. 6) and in the identity of the polypeptides of each protein family.…”

“…less than 50 ng in 100 μg of venom proteins) to known protein families (Tables 1 and 2). Supporting the view that venom proteomes are mainly composed of toxins belonging to a few protein families [4,[9][10][11][12][13][14][16][17][18][19][20][21][22][23][24], the proteins found in the venoms of L. muta and L. stenophrys cluster, respectively, in 8 and 7 different families (bradykinin-potentiating peptides, NGF, PLA 2 , serine proteinase, cysteine-rich secretory proteins (CRISP; only found in L. muta), C-type lectins, L-amino acid oxidase (LAO), and Zn 2+ -dependent metalloproteinases) (Fig. 6), whose relative abundances are listed in Table 3.…”

“…Transcriptomic investigations provide catalogues of partial and full-length transcripts that are synthesized by the venom gland. Here, we report a proteomic analysis of L. muta venom, which complements the study of snake venom gene transcriptional activity (transcriptome) in the same species [23] by showing the relative abundance of the various protein families that are actually secreted into the venoms.…”

“…Within-and between-species heterogeneity of venoms may also account for differences in the clinical symptoms observed in accidental envenomations. In order to explore the putative venom components, several laboratories have carried out transcriptomic analyses of the venom glands of viperid (Bitis gabonica [16], Bothrops insularis [17], Bothrops jararacussu [18], Bothrops jararaca [19], Agkistrodon acutus [20,21], Echis ocellatus [22], and Lachesis muta [23]), elapid (Oxyuramus scutellatus [24]), and colubrid (Philodryas olfersii [25]) snake species. Transcriptomic investigations provide catalogues of partial and full-length transcripts that are synthesized by the venom gland.…”

Snake Venomics and Antivenomics of the Arboreal Neotropical Pitvipers Bothriechis lateralis and Bothriechis schlegelii

“…72 All phylogenies indicate an early cladogenetic event splitting New Word pitvipers into temperate (Agkistrodon, Crotalus, and Sistrurus) and Neotropical (bothropoid genera and Lachesis) groups. 13 The lack of evidence for the occurrence of Kazal-type proteins (or messengers) in the venom proteomes and transcriptomes of species of genera Agkistrodon, 34,35 Sistrurus, 22,24 Bothrops, 26,[31][32][33] and Lachesis, 37 would support the hypothesis B. schlegelii(B).…”