Colubrid Venom Composition: An -Omics Perspective

Abstract

Snake venoms have been subjected to increasingly sensitive analyses for well over 100 years, but most research has been restricted to front-fanged snakes, which actually represent a relatively small proportion of extant species of advanced snakes. Because rear-fanged snakes are a diverse and distinct radiation of the advanced snakes, understanding venom composition among “colubrids” is critical to understanding the evolution of venom among snakes. Here we review the state of knowledge concerning rear-fanged snake venom composition, emphasizing those toxins for which protein or transcript sequences are available. We have also added new transcriptome-based data on venoms of three species of rear-fanged snakes. Based on this compilation, it is apparent that several components, including cysteine-rich secretory proteins (CRiSPs), C-type lectins (CTLs), CTLs-like proteins and snake venom metalloproteinases (SVMPs), are broadly distributed among “colubrid” venoms, while others, notably three-finger toxins (3FTxs), appear nearly restricted to the Colubridae (sensu stricto). Some putative new toxins, such as snake venom matrix metalloproteinases, are in fact present in several colubrid venoms, while others are only transcribed, at lower levels. This work provides insights into the evolution of these toxin classes, but because only a small number of species have been explored, generalizations are still rather limited. It is likely that new venom protein families await discovery, particularly among those species with highly specialized diets.

Venoms of Rear-Fanged Snakes: New Proteins and Novel Activities

“…Only SVMPs of the P-III class has been reported in RFS (Saviola et al, 2014;Junqueira-de-Azevedo et al, 2016), with the exception of one truncated SVMP of a new class (Campos et al, 2016). This new type of SVMP was identified in the RFS P. mertensi, in which a P-III SVMP was discovered to be truncated in the middle of the disintegrin-like domain by a nonsense mutation in the gene; the resulting truncated SVMP was also observed in the venom (Campos et al, 2016).…”

“…Even as phylogenetically diverse as venomous snakes are, there are some venom proteins commonly observed in all snake venoms. These include three-finger toxins (3FTxs), snake venom metalloproteinases (SVMPs), C-type lectins (CTLs), and cysteine-rich secretory proteins (CRiSPs) (Mackessy, 2010b;Junqueira-de-Azevedo et al, 2016). Phospholipase A 2 s (PLA 2 ) are ubiquitous in FFS venoms (Mackessy, 2010b), but have been found to be abundant in only a few RFS species (Hill and Mackessy, 2000;Huang and Mackessy, 2004).…”

“…Elapid venoms are the most well-known sources of 3FTxs (Fry et al, 2003b), but 3FTxs have been documented in the venoms of many RFS species (Fry et al, 2003a(Fry et al, , 2008Pawlak et al, 2006Pawlak et al, , 2009Heyborne and Mackessy, 2013;Junqueira-de-Azevedo et al, 2016) and can make up large portions of these venoms, as much as 84-92% of the total venom composition (Pla et al, 2017a;Modahl et al, 2018b). Rear-fanged snake genera that have abundant proteins in the molecular mass range of 3FTxs include Boiga, Spilotes, Trimorphodon, Oxybelis, Leioheterodon, Psammophis, Rhamphiophis, and Thelotornis (Figure 2A).…”

“…There are over 3,700 recognized extant snake species (Uetz et al, 2018); however, the minority of these, <20%, are known to have venoms that result in medically significant bites to humans (Uetz et al, 2018; www.toxinology.com 1 ). Snakebites from venomous snakes that are of medical concern are predominately front-fanged snakes from the families Viperidae and Elapidae, but a large number of snakes from various other families, previously classified as the single family Colubridae, have been discovered to be rear-fanged and also venomproducing (reviewed in Mackessy, 2002;Saviola et al, 2014;Junqueira-de-Azevedo et al, 2016).…”

“…These more complete venom gland transcriptomes and venom proteomes have revealed common patterns of toxin expression and secretion for RFS (Junqueira- de-Azevedo et al, 2016), as well as identified new venom proteins that had previously not been recognized as venom components in FFS species (OmPraba et al, 2010;Ching et al, 2012;Fry et al, 2012b;Campos et al, 2016). Further, these venoms have been shown to possess toxins with unique activities, such as prey-specific toxicity (Mackessy et al, 2006;Pawlak et al, 2006Pawlak et al, , 2009Heyborne and Mackessy, 2013;Modahl et al, 2018b).…”