Molecular Evolution and Phylogeny of Elapid Snake Venom Three-Finger Toxins

Abstract

Abstract. Animal venom components are of considerable interest to researchers across a wide variety of disciplines, including molecular biology, biochemistry, medicine, and evolutionary genetics. The three-finger family of snake venom peptides is a particularly interesting and biochemically complex group of venom peptides, because they are encoded by a large multigene family and display a diverse array of functional activities. In addition, understanding how this complex and highly varied multigene family evolved is an interesting question to researchers investigating the biochemical diversity of these peptides and their impact on human health. Therefore, the purpose of our study was to investigate the long-term evolutionary patterns exhibited by these snake venom toxins to understand the mechanisms by which they diversified into a large, biochemically diverse, multigene family. Our results show a much greater diversity of family members than was previously known, including a number of subfamilies that did not fall within any previously identified groups with characterized activities. In addition, we found that the long-term evolutionary processes that gave rise to the diversity of three-finger toxins are consistent with the birth-and-death model of multigene family evolution. It is anticipated that this ''three-finger toxin toolkit'' will prove to be useful in providing a clearer picture of the diversity of investigational ligands or potential therapeutics available within this important family.

Two color morphs of the pelagic yellow-bellied sea snake, Pelamis platura, from different locations of Costa Rica: Snake venomics, toxicity, and neutralization by antivenom

“…Among the various 3FTx components of P. platura venom, internal peptide sequences characteristic of both "short-chain" (type I) and "long-chain" (type II) subgroups of this protein family were identified (Table 1), in agreement with the early origin of these two types of 3FTx in elapid snakes, before the division between terrestrial Australian elapids and sea snakes, and terrestrial African and Asian elapids [53]. 3FTxs often display -neurotoxic activity by means of their high-affinity binding to nicotinic acetylcholine receptor in the motor end-plate at the neuromuscular junction of diverse groups of animals [54], therefore showing potent paralyzing and lethal effects.…”

“…The ability of the CSL antivenom in neutralizing the toxicity of the venoms of true sea snakes as well as that of the taxonomically divergent yellow-lipped sea krait, Laticauda colubrina [75], is consistent with the parallel but independent streamlining of both marine lineages, and the low level of phylogenetic variation of their 3FTxs [53,76].…”

Peptides as toxins/defensins

“…Snake venom has evolved to have linear peptides that act on the receptors localized on the endothelium surface. These peptides form their secondary structure upon interacting with the targeted receptors, and this generally produces a decrease in the blood pressure of the victims (Fry et al 2003;Fry 2005). The skin secretions of many amphibian groups contain linear polycationic and/or polyanionic peptides that are structurally simple and have antimicrobial activities (Nicolas et al 2003).…”

Dynamic evolution of venom proteins in squamate reptiles

“…Here we propose that the same process may be responsible for some instances of reverse recruitment, with a gene expressed in the venom gland being duplicated (which occurs frequently in a number of toxin families [21][22][23][24][25][26] ) and undergoing adaptive evolution to neofunctionalise the encoded protein for physiological expression (Fig. 6).…”