Evolutionary-tinkering of the snake venom system


In various studies, I have used multidisciplinary techniques to examine the snake venom system structural diversification, toxin recruitment event timings or toxin molecular evolution across the full-range of the ~100 million year old advanced snake clade, with a particular emphasis upon families that have not secondarily evolved front-fanged venom system (~80% of the 2500 species). Analyses revealed complex venoms with high levels of sequence in all lineages, including mutations in structural and functional residues, changes in cysteine spacing, and major deletions/truncations. Venom gland morphological analysis comprising gross dissection, histology and magnetic resonance imaging also demonstrated extensive modification of the venom system architecture.  Further, a reduction in the size and complexity of the venom system was observed in species in which constriction has been secondarily evolved as the preferred method of prey capture (e.g. American ratsnakes) or dietary preference has switched from live-prey to eggs (e.g. African egg-eating snake or the marbled sea snake) or to slugs/snails. Investigation of the timing of toxin recruitment events across the entire advanced snake radiation revealed that the evolution of advanced venom systems in three front-fanged lineages was associated with recruitment of new toxin types or explosive diversification of existing toxin types. These results support the role of venom as a key evolutionary innovation in the diversification of advanced snakes and identify a potential role for non-front-fanged venom toxins as a rich source for lead compounds for drug design and development.

Relevant papers are:

Fry BG, Vidal N, Van der Weerd L, Kochva E, Renjifo C. (2009) Evolution and diversification of the Toxicofera reptile venom system. Journal of Proteomics 72:127-136

Vonk FJ, Admiraal JF, Jackson K, Reshef R, de Bakker MA, Vanderschoot K, van den Berge I, van Atten M, Burgerhout E, Beck A, Mirtschin PJ, Kochva E, Witte F, Fry BG, Woods AE, Richardson MK. (2008) Evolutionary origin and development of snake fangs. Nature. 454(7204):630-3.

Fry BG, Scheib H, van der Weerd L, Young B, McNaughtan J, Ramjan SFR, Vidal N, Poelmann RE, Norman JA (2008) Evolution of an arsenal: structural and functional diversification of the venom system in the advanced snakes (Caenophidia). Molecular & Cellular Proteomics 7(2):215-46

Fry BG, Vidal N, Norman JA, Vonk FJ, Scheib H, Ramjan R, Kuruppu S, Fung K, Hedges SB, Richardson MK, Hodgson WC, Ignjatovic V, Summerhayes R and Kochva E (2006) Early evolution of the venom system in lizards and snakes. Nature 439(7076):509-632; Advance online publication November 17, 2005 doi:10.1038/nature04328.  Cited by Faculty of 1000.

Fry, BG (2005) “From genome to ‘venome’: Molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins.”  Genome Research 15:403-420

Li M, Fry BG, Kini RM (2005) “Putting the brakes on snake venom evolution: the unique molecular evolutionary patterns of Aipysurus eydouxii (Marbled sea snake) phospholipase A2 toxins.” Molecular Biology and Evolution 22(4):934-941.

Li M, Fry BG, Kini RM (2005) “Eggs only diet: the shift in preferred prey by the Marbled sea snake (Aipysurus eydouxii) resulting in a loss of postsynaptic neurotoxicity.”  Journal of Molecular Evolution 60(1):81-9.

Fry BG, Wüster W (2004) “Assembling an arsenal: Origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences”. Molecular Biology and Evolution 21(5): 870-883

Fry BG, Lumsden N, Wüster W, Wickramaratna J, Hodgson WC, Kini RM. (2003) “Isolation of a neurotoxin (alpha-colubritoxin) from a ‘non-venomous’ colubrid: evidence for early origin of venom in snakes. Journal of Molecular Evolution  57(4):446-452.

Fry BG, Wuster W, Kini RM., Brusic V, Khan A, Venkataraman D, Rooney AP. (2003) “Molecular evolution of elapid snake venom three finger toxins” Journal of Molecular Evolution 57(1):110-129.