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Review

A Review and Database of Snake Venom Proteomes

Clinical Toxicology Research Group, University of Newcastle, Newcastle 2298, Australia
*
Author to whom correspondence should be addressed.
Submission received: 1 September 2017 / Revised: 15 September 2017 / Accepted: 15 September 2017 / Published: 18 September 2017
(This article belongs to the Section Animal Venoms)

Abstract

:
Advances in the last decade combining transcriptomics with established proteomics methods have made possible rapid identification and quantification of protein families in snake venoms. Although over 100 studies have been published, the value of this information is increased when it is collated, allowing rapid assimilation and evaluation of evolutionary trends, geographical variation, and possible medical implications. This review brings together all compositional studies of snake venom proteomes published in the last decade. Compositional studies were identified for 132 snake species: 42 from 360 (12%) Elapidae (elapids), 20 from 101 (20%) Viperinae (true vipers), 65 from 239 (27%) Crotalinae (pit vipers), and five species of non-front-fanged snakes. Approximately 90% of their total venom composition consisted of eight protein families for elapids, 11 protein families for viperines and ten protein families for crotalines. There were four dominant protein families: phospholipase A2s (the most common across all front-fanged snakes), metalloproteases, serine proteases and three-finger toxins. There were six secondary protein families: cysteine-rich secretory proteins, l-amino acid oxidases, kunitz peptides, C-type lectins/snaclecs, disintegrins and natriuretic peptides. Elapid venoms contained mostly three-finger toxins and phospholipase A2s and viper venoms metalloproteases, phospholipase A2s and serine proteases. Although 63 protein families were identified, more than half were present in <5% of snake species studied and always in low abundance. The importance of these minor component proteins remains unknown.

Graphical Abstract

1. Introduction

Medically significant venomous snakes are almost entirely front-fanged, and are classified into three families: Atractaspidae (Burrowing Asps, 69 species), Elapidae (Elapids, 360 species), and Viperidae (Vipers, 340 species). This last family is in turn divided into two subfamilies, Viperinae (True Vipers, 101 species), and Crotalinae (Pit Vipers, 239 species) (data taken from www.reptile-database.org). The venom glands of caenophidian (advanced) snakes are homologous [1], and current evidence suggests that the three families of front-fanged snakes evolved from non-front-fanged venomous snakes [2].
Snake venoms are mixtures of different protein families, and each of these families contains many different toxins or toxin isoforms. As snake venom glands are homologous, it would be expected that some toxin families would be ubiquitous across the three front-fanged snake families. This ancestral venom proteome has since diversified among different snake families due to the influence of genetic mutations, genetic drift, and natural selection differentially molding the venom of each species to confer optimal prey specific toxicity.
For decades, a major line of research in snake venom studies has been investigating the structure and function of single toxins. Recent advances in the last decade in transcriptomics technology, combined with well-established proteomics methods such as reverse-phase high performance liquid chromatography (RP-HPLC), and mass spectrometry (MS), has enabled rapid identification of different toxins in snake venoms, as well as the ability to rapidly measure their relative abundance. These technological advances have fortuitously coincided with major improvements in our understanding of snake evolutionary relationships (phylogeny). As the venom proteomes of over 100 snake species have now been published, there is a sufficient number of studies to allow the general themes in snake venom evolution to begin to be understood. There is a need to collate this data for each family/subfamily of snakes for comparative analysis. This review collects all the studies published in the last ten years that provide relatively complete compositional abundances of the toxins in snake venoms. It could thenform the basis of an online database to be continually expanded as the venom profiles of more snake species are added to the body of knowledge.

2. Results

Compositional venom studies were identified for 132 species of snakes: 42 species from 360 (12%) Elapididae (elapids), 20 species from 101 (20%) Viperinae (true vipers), 65 species from 239 (27 %) Crotalinae (pit vipers), and five species of non-front-fanged snakes (percentage unknown—perhaps <3%). A total of 63 protein families were identified in all of the studies in the venoms of the 130 snake species reviewed. Of the 127 species of front-fanged snakes, their venom contained 59 protein families. For this group, with only a few exceptions, approximately 90% of their total venom composition was made up of eight protein families for elapids (Table 1 and Figure 1), 11 protein families for viperines (Table 2 and Figure 1), and ten protein families for crotalines (Table 3 and Figure 1). Three species (two elapids and one crotaline) had unusual venom compositions (Tables S1 and S2).
The 59 protein families could be classified based on compositional abundance and ubiquity. These categories were: four dominant protein families: phospholipase A2s (PLA2), metalloproteases (SVMP), serine proteases (SVSP) and three-finger toxins (3FTx); six secondary protein families: cysteine-rich secretory proteins (CRiSP), l-amino acid oxidases (LAAO), kunitz peptides (KUN), C-type lectins/snaclecs (CTL), disintegrins (DIS) and natriuretic peptides (NP); nine “minor” protein families; and 36 “rare” protein families (Table S3). There was also a further group of four “unique” protein families, which were each restricted to a single genus.
The major difference between elapid and viper venoms was the presence of 3FTx in elapid venoms and the virtual absence of 3FTx in viper venoms. Elapid venoms were also less diverse in the range or number of protein families, largely consisting of only PLA2 and 3FTx, although different groups were dominated by one or the other (Figure 2). Elapid venoms were more variable in the amount of different protein families compared to viper venoms.
Protein families in non-front-fanged snakes are included in Table S4.

3. Discussion

A total of 63 protein families were identified in the venoms of the 132 snake species included in this review. As the venom composition of only five species of non-front-fanged snake species were found, we will focus on the 127 species of front-fanged snakes, which contain 59 different protein families. Despite this diversity, with only a few exceptions, more than 90% of elapid and viper venoms were composed of just ten protein families (Figure 1). Based on their compositional importance and ubiquity, these 59 protein families were classified into five groups.
  • Dominant protein families (four families): PLA2, SVMP, SVSP and 3FTx.
  • Secondary protein families (six families that were commonly present, but in much smaller amounts than the dominant families): KUN, CRiSP, LAAO, CTL, DIS, and NP.
  • Minor protein families (nine families): acetylcholinesterase, hyaluronidase, 5′ nucleotidase, phosphodiesterase, phospholipase B, nerve growth factor, vascular endothelial growth factor, vespryn/ohanin and snake venom metalloprotease inhibitor.
  • Rare protein families: 36 families listed in Table S3.
  • Unique protein families (four families): defensins, waglerin, maticotoxin and cystatins. These families make up to 38% of the whole venom of a single species, but are classified separately as each is present in only one genus.
Both elapid and viper venoms were dominated by two or three protein families, PLA2s and 3FTxs for elapids and SVMPs, PLA2s and SVSPs for vipers (Figure 1). These protein families made up on average 83% and 67% of the venom proteome of elapids and vipers, respectively. Viper venoms consisted mainly of PLA2, SVMP and SVSP, but the variability in the amounts of different protein families between different groups of vipers was less than for elapids.
There was then a secondary group of six protein families, which made up 11% and 22% of the venom proteome of elapids and vipers, respectively. The remainder of the venoms consisted of minor abundance protein families belonging to nine minor protein families and 36 rare protein families, which were only present in a few species and in small amounts (nearly always less than 2%) (Table S3). It is unknown if these protein families are vestigial relics of snake evolutionary history (redundant, due to acquired prey immunity), or are recent genetic mutations.
There were four unique protein families, each only present in one genus but often making up the dominant fraction in the venom: Defensins, Crotalus; Waglerin, Tropidolaemus; Maticotoxin, Calliophis; and Cystatins, Bitis. Cystatins placement in this category was somewhat arbitrary, as it only comprised 2–10% of the venom, but was present in four of the five Bitis species studied and in no other snake species apart from the extremely aberrant Calliophis.

3.1. Dominant Protein Families

Phospholipase A2s. This was the most widespread protein family in elapids and vipers. However, the type of PLA2 differed between families with pancreatic type I in elapids and synovial-type II in vipers [99]. Maximum recorded amounts were 90% for Pseudechis papuanus (elapid), 51% for Agkistrodon contortrix (crotaline) and 65% for Vipera nikolskii (viperine).
Three-finger toxins. These toxins were only present in elapids (except for one Crotaline Atropoides nummifer <0.1%). In elapids, they made up to 95% of the total venom (Micrurus tschudii) and were present in 98% of all species. 3FTxs have been only recorded in small quantities in several viper species in other studies; Lachesis muta [100], Sistrurus catenatus [101], Protobothrops [54] and Daboia russelii [102].
Metalloproteases. This was the major protein family in viper venoms, present in all of the viper species included. The maximum amounts present were 72% for viperines (Echis ocellatus), and 85% for crotalines (Bothrops atrox). They were of lesser importance in elapids. Although they were present in 88% of species, they made up a much smaller proportion of the venom; maximum amounts recorded were 19% for Calliophis bivirgata and 12% for Ophiophagus hannah.
Serine proteases. These were the least quantitatively important of the dominant protein group. They were present in almost all vipers with the maximum amounts being 31% (Vipera berus) and 93% (Ovophis okinavensis). They were only present in 29% of elapids with the maximum amount being 6% for Notechis scutatus. However, they may potentially make up to 15% in some other Australian elapids, such as Pseudonaja textilis (Tasoulis et al. unpublished), because there are few proteomic studies of Australian elapids and it is well known that SVSPs are of major importance in Australian snakes as procoagulants [103,104].

3.2. Secondary Protein Families

Kunitz peptides. This family was the major venom component in black mambas (61%). This protein family was entirely absent from crotalines and, in viperines, was common in only three genera: Bitis, Macrovipera and Daboia. As crotalines are a derived viperine, this suggests that their absence in crotalines is the result of a reversal or secondary loss. Amongst other elapids, they may make up to 13% of the total venom.
l-amino acid oxidases. These enzymes were most common in crotalines in both the number of species that contained them (91% of all species) and in proportion of a single species venom with a maximum of 20% in Rhinocerophis cotiara. They were of relatively equal importance in elapids and viperines, always present in more than half the species and in amounts up to 6%.
Cysteine-rich secretory proteins. This group was widespread across all families, but more common in vipers (88% of species) than elapids (56% of species). The maximum amounts recorded in individual snake venoms were 10% for elapids and 16% for vipers.
C-type lectins/snaclecs. These were only a minor component of elapid venoms (maximum amount 2%), but were present in 100% of viperine venoms with a maximum amount 22% in Daboia russelii and 88% of crotalines with a maximum amount of 31% in Bothrops insularis.
Disintegrins. This protein family was entirely absent in elapids and was of relatively equal importance in viperines (88% of species) and crotalines (68% of species). The maximum amounts were 18% and 17%, respectively, for viperines and crotalines.
Natriuretic peptides. This protein family was far more important in vipers than elapids. They were only recorded in 20% of elapids with a maximum amount of 3% in Dendroaspis polylepis. They were present in 35% of viperines with a maximum amount of 11% in Vipera berus and in 60% of crotalines with a maximum amount of 37% in Bothriechis nigroviridis.

3.3. Major Inter-Family Differences

A major difference between elapids and vipers was the virtual absence of 3FTxs from viper venoms, while being one of the two dominant protein families in elapid venoms. As noted by Aird et al. [54], while 3FTxs have been recorded from several viper venoms, it has been via transcriptomics studies, not proteomic approaches. Vespryns/ohanins were only recorded in elapid venoms, with only three exceptions, none exceeding 0.5% (Agkitrodon bilineatus, Bothropoides pauloensis and Crotalus viridus—all crotalines). Conversely, DISs were absent in elapids while occurring in almost all viper venoms (averaging 2–6%). Another protein family conforming to this trend was CTLs, which again were a common component in viper venoms (averaging 6–8%), but were a minor component in elapid venoms, only present in about a third of the species, and in amounts not more than 2%. A similar trend was also apparent for NPs.

3.3.1. Elapids

Remarkably, for about 90% of the elapids, greater than 75% of their total venom composition was made up of just two protein families: PLA2s and 3FTxs. Lomonte et al. [32] drew attention to the divergence in venom phenotypes exhibited by New World coral snakes (Micrurus). There is a sharp dichotomy among species in the relative proportions of PLA2s and 3FTxs in their venoms. Our study shows that there is also a dichotomy in the proportion of PLA2s and 3FTxs in elapids on the Australian continent (Figure 2). The medically important Australo-Papuan elapids (Elapidae: Hydrophiinae) are dominated by PLA2s and the smaller and less important elapids contain mainly 3FTxs, similar to the Afro-Asian cobra venoms which are also mainly 3FTxs. Lomonte et al. [32] suggested that based on the known phylogeny, 3FTxs could be the ancestral state in coral snakes, with an evolutionary trend towards a greater preponderance of PLA2. Interestingly, when mapped onto the currently accepted phylogenies, all the most basal species in every clade of Australo-Papuan elapids have venom that is predominately composed of 3FTxs, while the derived species possess venom dominated by PLA2s. This suggests that this trend has happened repeatedly in the Australia–New Guinea region: New Guinea terrestrial elapids [105], Australian terrestrial elapids [106,107] and sea snakes [108,109]. However, this is based on the proteomics of only a few species and requires further investigation.
Kraits (Bungarus) are also dominated by PLA2s, making up almost half the venoms with less 3FTxs, similar to the medically important Australian elapids. However, they contain larger amounts of the secondary protein families—KUNs, LAAOs and CRiSPs—compared to other elapid groups.
The venoms of most cobra (Naja), species are dominated by 3FTxs, with less PLA2s. Interestingly, there is a similar dichotomy between cobras and kraits in proportions of PLA2s and 3FTxs, to coral snakes and Australo-Papuan elapids (Figure 2). Cobras also lacked many of the secondary protein families, except for CRiSPs, which are present in relatively large amounts in two species (both non-spitting species), N. haje (10%) and N. melanoleuca (7.6%). The venoms of the African spitting cobras were the most simplistic of all cobra species in the number of different protein families making up their venom.
Apart from Calliophis, Dendroaspis (Mambas), had the most unique venoms of the elapids, having no PLA2s, but instead containing specialized KUNs (dendrotoxins—Kv1 channel blockers) and 3FTxs modified into both acetylcholinesterase inhibitors (fasciculins) and l-type calcium channel blockers (calciseptines). Additionally, the KUNs are present in Dendroaspis in far greater amounts than in any other elapid species.
The most aberrant venom displayed by any elapid species was the Malayan blue coral snake Calliophis bivirgata flaviceps, which possessed the highest amounts of vespryn/ohanin of any elapid species (14%) and unusually high amounts of SVMPs for an elapid (19%). Even more unusual, almost a quarter of its venom consisted of a unique protein family, maticotoxin A, a cytotoxin. The highly aberrant venoms of these genera could indicate an ancient phylogenetic divergence.

3.3.2. Vipers

Viperine and crotaline venoms were quite similar, being composed mainly of three dominant protein families: PLA2s, SVMPs and SVSPs (Figure 1). The major difference between the two subfamilies was that KUNs were present in viperines and absent in crotalines. Additionally, crotalines possessed glutaminyl cyclases which were absent from viperine venoms. Some protein families were restricted to a single genus, such as defensins (crotamine), which were only found in the crotaline genus Crotalus (rattlesnakes), while cystatins were only found in the viperine genus Bitis. Both of these were present in significant amounts. The results confirmed the longstanding paradigm that viperid venoms consist of predominately hemotoxins, hemorrhagins, myotoxins and cytotoxins.
Few obvious trends were discernible in crotaline venoms at a protein family level, with less variability across the family (Figure 3). Lachesis has generally higher amounts of NPs than most crotalines, in addition to having relatively large amounts of SVSPs. The meso-american genera Atropoides/Cerrophidion and Porthidium, all possessed noticeably large amounts of DIS, CRiSPs and CTLs. Asian crotalines could not be separated from American crotalines based on venom protein families, suggesting an interesting wide geographical similarity (Figure 3).
The most aberrant venom of any viperid was Tropidolaemus. In addition to having 38% of its venom being represented by a unique protein family waglerin, the three dominant protein families in other viperid venoms made up only 15% of its venom proteome.

3.4. Medical Implications

PLA2s are present in 95% of the two most medically important snake families (elapids and vipers), excepting the limitation that there are some important groups of snakes that have not been investigated. Having a common protein family so widely spread has useful implications, such as making it possible to develop an assay that tests for the presence of snake venom in human body fluids. This has been shown for a limited number of snakes, in which measurement of phospholipase activity in patient samples identified patients with viper and elapid envenomation [110].
Demonstrating that there is a limited number of protein families in snake venoms, which is even more limited for major snake families or sub-families, supports efforts to develop universal anti-venoms [111].This explains the cross-neutralization of venoms by different anti-venoms, such as Asian and Australian anti-venoms cross-neutralizing neurotoxicity [112], and cross-neutralization of pit-viper venoms [113].

3.5. Evolutionary Biology

It has been known for some time that snake venoms are homologous and restricted to a small number of clearly successful protein families [114,115]. These molecular scaffolds have undergone considerable evolutionary “tinkering” to maximize their lethality to prey. Due to its finer inter- and intra-genus level resolution, this review represents a new and complementary dataset which can supplement future research in evolutionary biology. Although the extreme potency of some snake venoms clearly argues for powerful positive directional selection, it is also highly likely that in many adaptive radiations of snakes venom variation is not the primary driver of speciation. New ecological opportunities are also important e.g., the unidirectional late Oligocene or early Miocene invasion of the Americas by crotalines and elapids [116], and climatic oscillations can act as engines of speciation (“species pump”) [117,118,119]. Venom is simply one of many competing traits being selected for [120], and is often of neutral selective value [121,122]. Therefore, toxin evolution cannot be considered in isolation to other species traits.
An additional consideration is that different protein families can be equally effective in immobilizing the same prey type. A classic example of this is comparing the African elapid, black mamba Dendroaspis polylepis and the Australian elapid, coastal taipan Oxyuranus scutellatus. As noted by Shine [123] these two species represent a remarkable instance of parallel evolution resembling each other in body size, general morphology (Figure 4), color, venom toxicity, fang length, “snap and release” bite, clutch size, hatchling size, rapid growth in juveniles, males growing larger than females and feeding primarily on mammals. Despite having the same diet, they have a completely different composition of protein families in their venom. Black mamba contains mostly KUNs and 3FTxs, while coastal taipans have PLA2s and SVSPs. About 25% of coastal taipans completely lack 3FTxs in their venom or they are present in very small amounts (Tasoulis et al. unpublished). To further compound the difference, taipan toxins are mainly enzymatic while mamba venoms are almost entirely non-enzymatic. However, some of these protein families have converged to target the central nervous system, although in different ways [124,125,126,127], while others have evolved to target different physiological systems, such as the procoagulant (prothrombin activator), in coastal taipan venom. Black mamba venom is devoid of coagulopathic enzymes [18].
Previous evolutionary studies on snake venom have investigated phylogeny-based comparisons [128], co-evolution of venom and prey [94,129,130,131,132,133], prey resistance to venom [134,135], gene loss and duplication [136,137,138,139], exon exchange [3,101,140] and venom ontogeny [141,142,143,144,145,146,147]. This database allows us to study snake venom evolution through deep time. It can be used in conjunction with studies aimed at unraveling the historical biogeography of particular lineages of venomous snakes that, due to the known geological and climatic history of their in situ evolution, represent model case studies of evolution. These studies can examine venom evolution at different hierarchical levels, inter and intra-generic, as well as intra-specific.
Examples of this are the recent studies done on Meso-American pit vipers Atropoides, Bothriechis, and Cerrophidion [148,149] that are providing strong support for an underlying biogeographic model which gives a robust framework for estimating temporal rates of change and divergence times. Ideally, the venoms of these snake genera would be studied in even finer resolution, not just at a protein family level, but a complete venom profile of all toxins and toxin isoforms. This data can then be compared with probable divergence times to show which toxins are undergoing accelerated evolution. Due to its enormous diversity, and lability, venom could prove to be a phenotypic trait par excellence for studying evolutionary biology.
Although the relative abundance of protein families can be rapidly altered by genetic drift, (e.g., founder effect), some conserved toxins may act as reliable biomarkers for tracing evolutionary history. The venom compositions of the species in the viperine genus Bitis (Table 2) show a perfect congruence with the phylogenetic relationships of this genus proposed by Wittenberg et al. 2015 [150]. There is also evidence that snakes with unique venom represent species of ancient phylogenetic divergence (e.g., Calliophis and Dendroaspis [151,152] and Tropidolaemus wagleri [153].
Dowell et al. [136], have shown how rattlesnake venoms can become simplified due to gene deletions resulting in the loss of toxins. Our data analysis also reveals numerous examples where protein groups appear to have been lost in individual species and entire genera. For example LAAOs and CRiSPs are present in all Bitis species examined except B. arietans. NPs and vascular endothelial growth factors are absent in all Bitis species examined except the sister species B. gabonica/rhinoceros. Given the homologous nature of these protein families and their ubiquity, these patterns are difficult to explain other than being the result of character reversals.
Finally, on broader scale, trends in snake venom evolution can be compared with venom evolution in other groups of venomous organisms.

4. Methods

An online search was conducted using MEDLINE (PubMed platform) and Google Scholar from May 2006 to September 2017 using the keywords “snake venom proteomics”, and “snake venomics”. In addition, because of their strong emphasis on publishing articles on snake venom, the contents of the following journals were searched for articles on snake venom proteomics published between May 2006 and September 2017: Journal of Proteome Research, Journal of Proteomics, Toxicon, and Toxins. In addition, the journal BMC Genomics was searched using the keywords “snake venom proteomics”. The reference lists for any studies found were then searched for additional studies. The search was restricted to English language publications. Only studies that showed the compositional abundance of each protein family were included. If multiple studies had been conducted on a single snake species, the most recent one (which usually had the finest resolution) was included. To eliminate possible differences caused by ontogenetic venom variation, only data for adult snakes was considered. In cases in which venom from a particular snake species had marked geographical variability, entries for each geographical region were incorporated. For transcriptomics studies, data was usually presented as both relative expression of toxin-encoding genes and genes detected in the venom gland by proteomics. In these instances, the proteomic data was used. Many studies did not use transcriptomics, but instead a combination of reverse-phase high performance chromatography and electrophoresis followed by trypsin digestion and mass spectrometry. Researchers often did not state the number of individuals used in the study; presumably, many studies were based on the venom of a single snake. Due to space limitations, as well as ease of assimilating the data, the tables presented in the Results Section include only the protein families that make up the majority of the total venom proteome. For convenience, snake species with anomalous protein families in their venom were placed in separate tables for each snake family/subfamily. The remaining minor abundance protein families were included as a separate list.

Supplementary Materials

The following are available online at www.mdpi.com/2072-6651/9/9/290/s1, Table S1: Elapid species with unusual venom composition, Table S2: The unusual venom composition of Tropidolaemus wagleri (Temple Pit Viper), Table S3: The remaining 36 protein families in viper and elapid venoms have been classed as rare protein families, Most have only been recorded in one or two species of snakes, and always made up less than 10% of the whole venom. Table S4: The five non-front fanged snakes included in the study with the proportion of the ten major protein families in each venom (expressed as % of total venom), which make up the majority of their venom proteome.

Acknowledgments

Both authors would like to thank Professor Stephen Duffull of the University of Otago for first suggesting the review. They would also like to express their thanks to Nick Evans and Brendan Schembri for allowing the use of their beautiful photographs (taken at considerable personal risk). T.T. would also like to thank Jennifer Robinson for her patience with information technology assistance. Both authors would also like to express their thanks to Dr. Nicholas Casewell, for providing the original data to his 2009 paper on Echis transcriptomics for more detailed analysis. The study was funded in part by an Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence ID1110343 and Geoff Isbister is funded by a NHMRC Senior Research Fellowship ID1061041.

Author Contributions

T.T. and G.K.I. designed the study. T.T. extracted, collated and analysed all the data and both authors contributed to writing the review.

Conflicts of Interest

The authors declare no conflict of interest. Any conclusions drawn are dependent on the accuracy of the original papers.

References

  1. Jackson, T.N.W.; Young, B.; Underwood, G.; McCarthy, C.; Kochva, E.; Vidal, N.; van der Weerd, L.; Nabuurs, R.; Dobson, J.; Whitehead, D.; et al. Endless forms most beautiful: The evolution of ophidian oral glands, including the venom system, and the use of appropriate terminology for homologous structures. Zoomorphology 2017, 136, 107–130. [Google Scholar] [CrossRef]
  2. Vonk, F.J.; Admiraal, J.F.; Jackson, K.; Reshef, R.; de Bakker, M.A.; Vanderschoot, K.; van den Berge, I.; van Atten, M.; Burgerhout, E.; Beck, A. Evolutionary origin and development of snake fangs. Nature 2008, 454, 630. [Google Scholar] [CrossRef] [PubMed]
  3. Doley, R.; Nguyen Ngoc Bao, T.; Reza, M.A.; Kini, R.M. Unusual accelerated rate of deletions and insertions in toxin genes in the venom glands of the pygmy copperhead (Austrelaps labialis) from kangaroo island. BMC Evol. Biol. 2008, 8, 1–13. [Google Scholar] [CrossRef] [PubMed]
  4. Chatrath, S.T.; Chapeaurouge, A.; Lin, Q.; Lim, T.K.; Dunstan, N.; Mirtschin, P.; Kumar, P.P.; Kini, R.M. Identification of Novel Proteins from the Venom of a Cryptic Snake Drysdalia coronoides by a Combined Transcriptomics and Proteomics Approach. J. Proteome Res. 2011, 10, 739–750. [Google Scholar] [CrossRef] [PubMed]
  5. Paiva, O.; Pla, D.; Wright, C.E.; Beutler, M.; Sanz, L.; Gutiérrez, J.M.; Williams, D.J.; Calvete, J.J. Combined venom gland cDNA sequencing and venomics of the New Guinea small-eyed snake, Micropechis ikaheka. J. Proteom. 2014, 110, 209–229. [Google Scholar] [CrossRef] [PubMed]
  6. Tan, C.H.; Tan, K.Y.; Tan, N.H. Revisiting Notechis scutatus venom: On shotgun proteomics and neutralization by the “bivalent” Sea Snake Antivenom. J. Proteom. 2016, 144, 33–38. [Google Scholar] [CrossRef] [PubMed]
  7. Herrera, M.; Fernández, J.; Vargas, M.; Villalta, M.; Segura, Á.; León, G.; Angulo, Y.; Paiva, O.; Matainaho, T.; Jensen, S.D.; et al. Comparative proteomic analysis of the venom of the taipan snake, Oxyuranus scutellatus, from Papua New Guinea and Australia: Role of neurotoxic and procoagulant effects in venom toxicity. J. Proteom. 2012, 75, 2128–2140. [Google Scholar] [CrossRef] [PubMed]
  8. Pla, D.; Bande, B.W.; Welton, R.E.; Paiva, O.K.; Sanz, L.; Segura, A.; Wright, C.E.; Calvete, J.J.; Gutierrez, J.M.; Williams, D.J. Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms. J. Proteom. 2017, 150, 201–215. [Google Scholar] [CrossRef] [PubMed]
  9. Calvete, J.J.; Ghezellou, P.; Paiva, O.; Matainaho, T.; Ghassempour, A.; Goudarzi, H.; Kraus, F.; Sanz, L.; Williams, D.J. Snake venomics of two poorly known Hydrophiinae: Comparative proteomics of the venoms of terrestrial Toxicocalamus longissimus and marine Hydrophis cyanocinctus. J. Proteom. 2012, 75, 4091–4101. [Google Scholar] [CrossRef] [PubMed]
  10. Laustsen, A.H.; Gutiérrez, J.M.; Rasmussen, A.R.; Engmark, M.; Gravlund, P.; Sanders, K.L.; Lohse, B.; Lomonte, B. Danger in the reef: Proteome, toxicity, and neutralization of the venom of the olive sea snake, Aipysurus laevis. Toxicon 2015, 107, 187–196. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  11. Lomonte, B.; Pla, D.; Sasa, M.; Tsai, W.-C.; Solórzano, A.; Ureña-Díaz, J.M.; Fernández-Montes, M.L.; Mora-Obando, D.; Sanz, L.; Gutiérrez, J.M.; et al. 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. J. Proteom. 2014, 103, 137–152. [Google Scholar] [CrossRef] [PubMed]
  12. Tan, C.H.; Tan, K.Y.; Lim, S.E.; Tan, N.H. Venomics of the beaked sea snake, Hydrophis schistosus: A minimalist toxin arsenal and its cross-neutralization by heterologous antivenoms. J. Proteom. 2015, 126, 121–130. [Google Scholar] [CrossRef] [PubMed]
  13. Tan, C.H.; Wong, K.Y.; Tan, K.Y.; Tan, N.H. Venom proteome of the yellow-lipped sea krait, Laticauda colubrina from Bali: Insights into subvenomic diversity, venom antigenicity and cross-neutralization by antivenom. J. Proteom. 2017, 166, 48–58. [Google Scholar] [CrossRef] [PubMed]
  14. Oh, A.M.F.; Tan, C.H.; Ariaranee, G.C.; Quraishi, N.; Tan, N.H. Venomics of Bungarus caeruleus (Indian krait): Comparable venom profiles, variable immunoreactivities among specimens from Sri Lanka, India and Pakistan. J. Proteom. 2017, 164, 1–18. [Google Scholar] [CrossRef] [PubMed]
  15. Rusmili, M.R.A.; Yee, T.T.; Mustafa, M.R.; Hodgson, W.C.; Othman, I. Proteomic characterization and comparison of Malaysian Bungarus candidus and Bungarus fasciatus venoms. J. Proteom. 2014, 110, 129–144. [Google Scholar] [CrossRef] [PubMed]
  16. Ziganshin, R.H.; Kovalchuk, S.I.; Arapidi, G.P.; Starkov, V.G.; Hoang, A.N.; Thi Nguyen, T.T.; Nguyen, K.C.; Shoibonov, B.B.; Tsetlin, V.I.; Utkin, Y.N. Quantitative proteomic analysis of Vietnamese krait venoms: Neurotoxins are the major components in Bungarus multicinctus and phospholipases A2 in Bungarus fasciatus. Toxicon 2015, 107, 197–209. [Google Scholar] [CrossRef] [PubMed]
  17. Lauridsen, L.P.; Laustsen, A.H.; Lomonte, B.; Gutiérrez, J.M. Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps). J. Proteom. 2016, 136, 248–261. [Google Scholar] [CrossRef] [PubMed]
  18. Laustsen, A.H.; Lomonte, B.; Lohse, B.; Fernández, J.; Gutiérrez, J.M. Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development. J. Proteom. 2015, 119, 126–142. [Google Scholar] [CrossRef] [PubMed]
  19. Malih, I.; Ahmad rusmili, M.R.; Tee, T.Y.; Saile, R.; Ghalim, N.; Othman, I. Proteomic analysis of Moroccan cobra Naja haje legionis venom using tandem mass spectrometry. J. Proteom. 2014, 96, 240–252. [Google Scholar] [CrossRef] [PubMed]
  20. Lauridsen, L.P.; Laustsen, A.H.; Lomonte, B.; Gutiérrez, J.M. Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca. J. Proteom. 2017, 150, 98–108. [Google Scholar] [CrossRef] [PubMed]
  21. Petras, D.; Sanz, L.; Segura, Á.; Herrera, M.; Villalta, M.; Solano, D.; Vargas, M.; León, G.; Warrell, D.A.; Theakston, R.D.G.; et al. Snake Venomics of African Spitting Cobras: Toxin Composition and Assessment of Congeneric Cross-Reactivity of the Pan-African EchiTAb-Plus-ICP Antivenom by Antivenomics and Neutralization Approaches. J. Proteome Res. 2011, 10, 1266–1280. [Google Scholar] [CrossRef] [PubMed]
  22. Shan, L.-L.; Gao, J.-F.; Zhang, Y.-X.; Shen, S.-S.; He, Y.; Wang, J.; Ma, X.-M.; Ji, X. Proteomic characterization and comparison of venoms from two elapid snakes (Bungarus multicinctus and Naja atra) from China. J. Proteom. 2016, 138, 83–94. [Google Scholar] [CrossRef] [PubMed]
  23. Huang, H.-W.; Liu, B.-S.; Chien, K.-Y.; Chiang, L.-C.; Huang, S.-Y.; Sung, W.-C.; Wu, W.-G. Cobra venom proteome and glycome determined from individual snakes of Naja atra reveal medically important dynamic range and systematic geographic variation. J. Proteom. 2015, 128, 92–104. [Google Scholar] [CrossRef] [PubMed]
  24. Xu, N.; Zhao, H.-Y.; Yin, Y.; Shen, S.-S.; Shan, L.-L.; Chen, C.-X.; Zhang, Y.-X.; Gao, J.-F.; Ji, X. Combined venomics, antivenomics and venom gland transcriptome analysis of the monocoled cobra (Naja kaouthia) from China. J. Proteom. 2017, 159, 19–31. [Google Scholar] [CrossRef] [PubMed]
  25. Tan, K.Y.; Tan, C.H.; Fung, S.Y.; Tan, N.H. Venomics, lethality and neutralization of Naja kaouthia (monocled cobra) venoms from three different geographical regions of Southeast Asia. J. Proteom. 2015, 120, 105–125. [Google Scholar] [CrossRef] [PubMed]
  26. Dutta, S.; Chanda, A.; Kalita, B.; Islam, T.; Patra, A.; Mukherjee, A.K. Proteomic analysis to unravel the complex venom proteome of eastern India Naja naja: Correlation of venom composition with its biochemical and pharmacological properties. J. Proteom. 2017, 156, 29–39. [Google Scholar] [CrossRef] [PubMed]
  27. Sintiprungrat, K.; Watcharatanyatip, K.; Senevirathne, W.D.S.T.; Chaisuriya, P.; Chokchaichamnankit, D.; Srisomsap, C.; Ratanabanangkoon, K. A comparative study of venomics of Naja naja from India and Sri Lanka, clinical manifestations and antivenomics of an Indian polyspecific antivenom. J. Proteom. 2016, 132, 131–143. [Google Scholar] [CrossRef] [PubMed]
  28. Tan, N.H.; Wong, K.Y.; Tan, C.H. Venomics of Naja sputatrix, the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization. J. Proteom. 2017, 157, 18–32. [Google Scholar] [CrossRef] [PubMed]
  29. Petras, D.; Heiss, P.; Süssmuth, R.D.; Calvete, J.J. Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches. J. Proteome Res. 2015, 14, 2539–2556. [Google Scholar] [CrossRef] [PubMed]
  30. Fernández, J.; Vargas-Vargas, N.; Pla, D.; Sasa, M.; Rey-Suárez, P.; Sanz, L.; Gutiérrez, J.M.; Calvete, J.J.; Lomonte, B. Snake venomics of Micrurus alleni and Micrurus mosquitensis from the Caribbean region of Costa Rica reveals two divergent compositional patterns in New World elapids. Toxicon 2015, 107, 217–233. [Google Scholar] [CrossRef] [PubMed]
  31. Corrêa-Netto, C.; Junqueira-de-Azevedo, I.d.L.M.; Silva, D.A.; Ho, P.L.; Leitão-de-Araújo, M.; Alves, M.L.M.; Sanz, L.; Foguel, D.; Zingali, R.B.; Calvete, J.J. Snake venomics and venom gland transcriptomic analysis of Brazilian coral snakes, Micrurus altirostris and M. corallinus. J. Proteom. 2011, 74, 1795–1809. [Google Scholar] [CrossRef] [PubMed]
  32. Lomonte, B.; Rey-Suárez, P.; Fernández, J.; Sasa, M.; Pla, D.; Vargas, N.; Bénard-Valle, M.; Sanz, L.; Corrêa-Netto, C.; Núñez, V.; et al. Venoms of Micrurus coral snakes: Evolutionary trends in compositional patterns emerging from proteomic analyses. Toxicon 2016, 122, 7–25. [Google Scholar] [CrossRef] [PubMed]
  33. Rey-Suárez, P.; Núñez, V.; Fernández, J.; Lomonte, B. Integrative characterization of the venom of the coral snake Micrurus dumerilii (Elapidae) from Colombia: Proteome, toxicity, and cross-neutralization by antivenom. J. Proteom. 2016, 136, 262–273. [Google Scholar] [CrossRef] [PubMed]
  34. Margres, M.J.; Aronow, K.; Loyacano, J.; Rokyta, D.R. The venom-gland transcriptome of the eastern coral snake (Micrurus fulvius) reveals high venom complexity in the intragenomic evolution of venoms. BMC Genom. 2013, 14, 531. [Google Scholar] [CrossRef] [PubMed]
  35. Rey-Suárez, P.; Núñez, V.; Gutiérrez, J.M.; Lomonte, B. Proteomic and biological characterization of the venom of the redtail coral snake, Micrurus mipartitus (Elapidae), from Colombia and Costa Rica. J. Proteom. 2011, 75, 655–667. [Google Scholar] [CrossRef] [PubMed]
  36. Fernandez, J.; Alape-Giron, A.; Angulo, Y.; Sanz, L.; Gutierrez, J.; Calvete, J.; Lomonte, B. Venomic and antivenomic analyses of the Central American Coral Snake, Micrurus nigrocinctus (Elapidae). J Proteome Res. 2011, 10, 1816–1827. [Google Scholar] [CrossRef] [PubMed]
  37. Sanz, L.; Pla, D.; Pérez, A.; Rodríguez, Y.; Zavaleta, A.; Salas, M.; Lomonte, B.; Calvete, J.J. Venomic Analysis of the Poorly Studied Desert Coral Snake, Micrurus tschudii tschudii, Supports the 3FTx/PLA2 Dichotomy across Micrurus Venoms. Toxins 2016, 8, 178. [Google Scholar] [CrossRef] [PubMed]
  38. Calvete, J.J.; Escolano, J.; Sanz, L. Snake Venomics of Bitis Species Reveals Large Intragenus Venom Toxin Composition Variation:  Application to Taxonomy of Congeneric Taxa. J. Proteome Res. 2007, 6, 2732–2745. [Google Scholar] [CrossRef] [PubMed]
  39. Fahmi, L.; Makran, B.; Pla, D.; Sanz, L.; Oukkache, N.; Lkhider, M.; Harrison, R.A.; Ghalim, N.; Calvete, J.J. Venomics and antivenomics profiles of North African Cerastes cerastes and C. vipera populations reveals a potentially important therapeutic weakness. J. Proteom. 2012, 75, 2442–2453. [Google Scholar] [CrossRef] [PubMed]
  40. Mukherjee, A.K.; Kalita, B.; Mackessy, S.P. A proteomic analysis of Pakistan Daboia russelii russelii venom and assessment of potency of Indian polyvalent and monovalent antivenom. J. Proteom. 2016, 144, 73–86. [Google Scholar] [CrossRef] [PubMed]
  41. Kalita, B.; Patra, A.; Mukherjee, A.K. Unraveling the Proteome Composition and Immuno-profiling of Western India Russell’s Viper Venom for In-Depth Understanding of Its Pharmacological Properties, Clinical Manifestations, and Effective Antivenom Treatment. J. Proteome Res. 2017, 16, 583–598. [Google Scholar] [CrossRef] [PubMed]
  42. Tan, N.H.; Fung, S.Y.; Tan, K.Y.; Yap, M.K.K.; Gnanathasan, C.A.; Tan, C.H. Functional venomics of the Sri Lankan Russell’s viper (Daboia russelii) and its toxinological correlations. J. Proteom. 2015, 128, 403–423. [Google Scholar] [CrossRef] [PubMed]
  43. Casewell, N.R.; Harrison, R.A.; Wüster, W.; Wagstaff, S.C. Comparative venom gland transcriptome surveys of the saw-scaled vipers (Viperidae: Echis) reveal substantial intra-family gene diversity and novel venom transcripts. BMC Genom. 2009, 10, 564. [Google Scholar] [CrossRef] [PubMed]
  44. Makran, B.; Fahmi, L.; Pla, D.; Sanz, L.; Oukkache, N.; Lkhider, M.; Ghalim, N.; Calvete, J.J. Snake venomics of Macrovipera mauritanica from Morocco, and assessment of the para-specific immunoreactivity of an experimental monospecific and a commercial antivenoms. J. Proteom. 2012, 75, 2431–2441. [Google Scholar] [CrossRef] [PubMed]
  45. Sanz, L.; Ayvazyan, N.; Calvete, J.J. Snake venomics of the Armenian mountain vipers Macrovipera lebetina obtusa and Vipera raddei. J. Proteom. 2008, 71, 198–209. [Google Scholar] [CrossRef] [PubMed]
  46. Göçmen, B.; Heiss, P.; Petras, D.; Nalbantsoy, A.; Süssmuth, R.D. Mass spectrometry guided venom profiling and bioactivity screening of the Anatolian Meadow Viper, Vipera anatolica. Toxicon 2015, 107, 163–174. [Google Scholar] [CrossRef] [PubMed]
  47. Latinović, Z.; Leonardi, A.; Šribar, J.; Sajevic, T.; Žužek, M.C.; Frangež, R.; Halassy, B.; Trampuš-Bakija, A.; Pungerčar, J.; Križaj, I. Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications. J. Proteom. 2016, 146, 34–47. [Google Scholar] [CrossRef] [PubMed]
  48. Kovalchuk, S.I.; Ziganshin, R.H.; Starkov, V.G.; Tsetlin, V.I.; Utkin, Y.N. Quantitative Proteomic Analysis of Venoms from Russian Vipers of Pelias Group: Phospholipases A2 are the Main Venom Components. Toxins 2016, 8, 105. [Google Scholar] [CrossRef] [PubMed]
  49. Fenwick, A.M.; Gutberlet, J.R.L.; Evans, J.A.; Parkinson, C.L. Morphological and molecular evidence for phylogeny and classification of South American pitvipers, genera Bothrops, Bothriopsis, and Bothrocophias (Serpentes: Viperidae). Zool. J. Linn. Soc. 2009, 156, 617–640. [Google Scholar] [CrossRef]
  50. Tang, E.L.H.; Tan, C.H.; Fung, S.Y.; Tan, N.H. Venomics of Calloselasma rhodostoma, the Malayan pit viper: A complex toxin arsenal unraveled. J. Proteom. 2016, 148, 44–56. [Google Scholar] [CrossRef] [PubMed]
  51. Zainal Abidin, S.A.; Rajadurai, P.; Hoque Chowdhury, M.E.; Ahmad Rusmili, M.R.; Othman, I.; Naidu, R. Proteomic Characterization and Comparison of Malaysian Tropidolaemus wagleri and Cryptelytrops purpureomaculatus Venom Using Shotgun-Proteomics. Toxins 2016, 8, 299. [Google Scholar] [CrossRef] [PubMed]
  52. Gao, J.-F.; Wang, J.; He, Y.; Qu, Y.-F.; Lin, L.-H.; Ma, X.-M.; Ji, X. Proteomic and biochemical analyses of short-tailed pit viper (Gloydius brevicaudus) venom: Age-related variation and composition–activity correlation. J. Proteom. 2014, 105, 307–322. [Google Scholar] [CrossRef] [PubMed]
  53. Yang, Z.-M.; Yang, Y.-E.; Chen, Y.; Cao, J.; Zhang, C.; Liu, L.-L.; Wang, Z.-Z.; Wang, X.-M.; Wang, Y.-M.; Tsai, I.-H. Transcriptome and proteome of the highly neurotoxic venom of Gloydius intermedius. Toxicon 2015, 107, 175–186. [Google Scholar] [CrossRef] [PubMed]
  54. Aird, S.D.; Watanabe, Y.; Villar-Briones, A.; Roy, M.C.; Terada, K.; Mikheyev, A.S. Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis). BMC Genom. 2013, 14, 1–62. [Google Scholar] [CrossRef] [PubMed]
  55. Aird, S.D. Ophidian envenomation strategies and the role of purines. Toxicon 2002, 40, 335–393. [Google Scholar] [CrossRef]
  56. Aird, S.D.; Aggarwal, S.; Villar-Briones, A.; Tin, M.M.; Terada, K.; Mikheyev, A.S. Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly. BMC Genom. 2015, 16, 647. [Google Scholar] [CrossRef] [PubMed]
  57. Villalta, M.; Pla, D.; Yang, S.L.; Sanz, L.; Segura, A.; Vargas, M.; Chen, P.Y.; Herrera, M.; Estrada, R.; Cheng, Y.F.; et al. Snake venomics and antivenomics of Protobothrops mucrosquamatus and Viridovipera stejnegeri from Taiwan: Keys to understand the variable immune response in horses. J. Proteom. 2012, 75, 5628–5645. [Google Scholar] [CrossRef] [PubMed]
  58. Lomonte, B.; Tsai, W.-C.; Ureña-Diaz, J.M.; Sanz, L.; Mora-Obando, D.; Sánchez, E.E.; Fry, B.G.; Gutiérrez, J.M.; Gibbs, H.L.; Sovic, M.G.; et al. Venomics of New World pit vipers: Genus-wide comparisons of venom proteomes across Agkistrodon. J. Proteom. 2014, 96, 103–116. [Google Scholar] [CrossRef] [PubMed]
  59. Bocian, A.; Urbanik, M.; Hus, K.; Łyskowski, A.; Petrilla, V.; Andrejčáková, Z.; Petrillová, M.; Legáth, J. Proteomic Analyses of Agkistrodon contortrix contortrix Venom Using 2D Electrophoresis and MS Techniques. Toxins 2016, 8, 372. [Google Scholar] [CrossRef] [PubMed]
  60. Angulo, Y.; Escolano, J.; Lomonte, B.; Gutiérrez, J.M.; Sanz, L.; Calvete, J.J. Snake Venomics of Central American Pitvipers: Clues for Rationalizing the Distinct Envenomation Profiles of Atropoides nummifer and Atropoides picadoi. J. Proteome Res. 2007, 7, 708–719. [Google Scholar] [CrossRef] [PubMed]
  61. Pla, D.; Sanz, L.; Sasa, M.; Acevedo, M.E.; Dwyer, Q.; Durban, J.; Pérez, A.; Rodriguez, Y.; Lomonte, B.; Calvete, J.J. Proteomic analysis of venom variability and ontogeny across the arboreal palm-pitvipers (genus Bothriechis). J. Proteom. 2017, 152, 1–12. [Google Scholar] [CrossRef] [PubMed]
  62. Fernández, J.; Lomonte, B.; Sanz, L.; Angulo, Y.; Gutiérrez, J.M.; Calvete, J.J. Snake Venomics of Bothriechis nigroviridis Reveals Extreme Variability among Palm Pitviper Venoms: Different Evolutionary Solutions for the Same Trophic Purpose. J. Proteome Res. 2010, 9, 4234–4241. [Google Scholar] [CrossRef] [PubMed]
  63. Lomonte, B.; Tsai, W.-C.; Bonilla, F.; Solórzano, A.; Solano, G.; Angulo, Y.; Gutiérrez, J.M.; Calvete, J.J. Snake venomics and toxicological profiling of the arboreal pitviper Bothriechis supraciliaris from Costa Rica. Toxicon 2012, 59, 592–599. [Google Scholar] [CrossRef] [PubMed]
  64. Salazar-Valenzuela, D.; Mora-Obando, D.; Fernández, M.L.; Loaiza-Lange, A.; Gibbs, H.L.; Lomonte, B. Proteomic and toxicological profiling of the venom of Bothrocophias campbelli, a pitviper species from Ecuador and Colombia. Toxicon 2014, 90, 15–25. [Google Scholar] [CrossRef] [PubMed]
  65. Calvete, J.J.; Borges, A.; Segura, Á.; Flores-Díaz, M.; Alape-Girón, A.; Gutiérrez, J.M.; Diez, N.; De Sousa, L.; Kiriakos, D.; Sánchez, E.; et al. Snake venomics and antivenomics of Bothrops colombiensis, a medically important pitviper of the Bothrops atrox-asper complex endemic to Venezuela: Contributing to its taxonomy and snakebite management. J. Proteom. 2009, 72, 227–240. [Google Scholar] [CrossRef] [PubMed]
  66. Gay, C.; Sanz, L.; Calvete, J.J.; Pla, D. Snake Venomics and Antivenomics of Bothrops diporus, a Medically Important Pitviper in Northeastern Argentina. Toxins 2016, 8, 9. [Google Scholar] [CrossRef] [PubMed]
  67. Jorge, R.J.B.; Monteiro, H.S.A.; Gonçalves-Machado, L.; Guarnieri, M.C.; Ximenes, R.M.; Borges-Nojosa, D.M.; Luna, K.P.d.O.; Zingali, R.B.; Corrêa-Netto, C.; Gutiérrez, J.M.; et al. Venomics and antivenomics of Bothrops erythromelas from five geographic populations within the Caatinga ecoregion of northeastern Brazil. J. Proteom. 2015, 114, 93–114. [Google Scholar] [CrossRef] [PubMed]
  68. Valente, R.H.; Guimarães, P.R.; Junqueira, M.; Neves-Ferreira, A.G.C.; Soares, M.R.; Chapeaurouge, A.; Trugilho, M.R.O.; León, I.R.; Rocha, S.L.G.; Oliveira-Carvalho, A.L.; et al. Bothrops insularis venomics: A proteomic analysis supported by transcriptomic-generated sequence data. J. Proteom. 2009, 72, 241–255. [Google Scholar] [CrossRef] [PubMed]
  69. Gonçalves-Machado, L.; Pla, D.; Sanz, L.; Jorge, R.J.B.; Leitão-De-Araújo, M.; Alves, M.L.M.; Alvares, D.J.; De Miranda, J.; Nowatzki, J.; de Morais-Zani, K.; et al. Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the Brazilian Atlantic rainforest. J. Proteom. 2016, 135, 73–89. [Google Scholar] [CrossRef] [PubMed]
  70. Sousa, L.F.; Nicolau, C.A.; Peixoto, P.S.; Bernardoni, J.L.; Oliveira, S.S.; Portes-Junior, J.A.; Mourão, R.H.V.; Lima-dos-Santos, I.; Sano-Martins, I.S.; Chalkidis, H.M.; et al. Comparison of Phylogeny, Venom Composition and Neutralization by Antivenom in Diverse Species of Bothrops Complex. PLoS Negl. Trop. Dis. 2013, 7, 1–16. [Google Scholar] [CrossRef] [PubMed]
  71. Rodrigues, R.S.; Boldrini-França, J.; Fonseca, F.P.P.; de la Torre, P.; Henrique-Silva, F.; Sanz, L.; Calvete, J.J.; Rodriques, V.M. Combined snake venomics and venom gland transcriptome analysis of Bothropoides pauloensis. J. Proteom. 2012, 75, 609–623. [Google Scholar] [CrossRef] [PubMed]
  72. Alape-Girón, A.; Flores-Díaz, M.; Sanz, L.; Madrigal, M.; Escolano, J.; Sasa, M.; Calvete, J.J. Studies on the venom proteome of Bothrops asper: Perspectives and applications. Toxicon 2009, 54, 938–948. [Google Scholar] [CrossRef] [PubMed]
  73. Sousa, L.F.; Portes-Junior, J.A.; Nicolau, C.A.; Bernardoni, J.L.; Nishiyama, M.Y., Jr.; Amazonas, D.R.; Freitas-de-Sousa, L.A.; Mourão, R.H.V.; Chalkidis, H.M.; Valente, R.H.; et al. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon. J. Proteom. 2017, 159, 32–46. [Google Scholar] [CrossRef] [PubMed]
  74. Núñez, V.; Cid, P.; Sanz, L.; De La Torre, P.; Angulo, Y.; Lomonte, B.; Gutiérrez, J.M.; Calvete, J.J. Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Perú and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism. J. Proteom. 2009, 73, 57–78. [Google Scholar] [CrossRef] [PubMed]
  75. Calvete, J.J.; Sanz, L.; Pérez, A.; Borges, A.; Vargas, A.M.; Lomonte, B.; Angulo, Y.; Gutiérrez, J.M.; Chalkidis, H.M.; Mourão, R.H.V.; et al. Snake population venomics and antivenomics of Bothrops atrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management. J. Proteom. 2011, 74, 510–527. [Google Scholar] [CrossRef] [PubMed]
  76. Kohlhoff, M.; Borges, M.H.; Yarleque, A.; Cabezas, C.; Richardson, M.; Sanchez, E.F. Exploring the proteomes of the venoms of the Peruvian pit vipers Bothrops atrox, B. barnetti and B. pictus. J. Proteom. 2012, 75, 2181–2195. [Google Scholar] [CrossRef] [PubMed]
  77. Mora-Obando, D.; Guerrero-Vargas, J.A.; Prieto-Sánchez, R.; Beltrán, J.; Rucavado, A.; Sasa, M.; Gutiérrez, J.M.; Ayerbe, S.; Lomonte, B. Proteomic and functional profiling of the venom of Bothrops ayerbei from Cauca, Colombia, reveals striking interspecific variation with Bothrops asper venom. J. Proteom. 2014, 96, 159–172. [Google Scholar] [CrossRef] [PubMed]
  78. Gutiérrez, J.M.; Sanz, L.; Escolano, J.; Fernández, J.; Lomonte, B.; Angulo, Y.; Rucavado, A.; Warrell, D.A.; Calvete, J.J. Snake Venomics of the Lesser Antillean Pit Vipers Bothrops caribbaeus and Bothrops lanceolatus: Correlation with Toxicological Activities and Immunoreactivity of a Heterologous Antivenom. J. Proteome Res. 2008, 7, 4396–4408. [Google Scholar] [CrossRef] [PubMed]
  79. Bernardes, C.P.; Menaldo, D.L.; Camacho, E.; Rosa, J.C.; Escalante, T.; Rucavado, A.; Lomonte, B.; Gutiérrez, J.M.; Sampaio, S.V. Proteomic analysis of Bothrops pirajai snake venom and characterization of BpirMP, a new P-I metalloproteinase. J. Proteom. 2013, 80, 250–267. [Google Scholar] [CrossRef] [PubMed]
  80. Fernández Culma, M.; Andrés Pereañez, J.; Núñez Rangel, V.; Lomonte, B. Snake venomics of Bothrops punctatus, a semiarboreal pitviper species from Antioquia, Colombia. PeerJ 2014, 2, e246. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  81. Lomonte, B.; Rey-Suárez, P.; Tsai, W.-C.; Angulo, Y.; Sasa, M.; Gutiérrez, J.M.; Calvete, J.J. Snake venomics of the pit vipers Porthidium nasutum, Porthidium ophryomegas, and Cerrophidion godmani from Costa Rica: Toxicological and taxonomical insights. J. Proteom. 2012, 75, 1675–1689. [Google Scholar] [CrossRef] [PubMed]
  82. Lomonte, B.; Fernández, J.; Sanz, L.; Angulo, Y.; Sasa, M.; Gutiérrez, J.M.; Calvete, J.J. Venomous snakes of Costa Rica: Biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics. J. Proteom. 2014, 105, 323–339. [Google Scholar] [CrossRef] [PubMed]
  83. Rokyta, D.R.; Lemmon, A.R.; Margres, M.J.; Aronow, K. The venom-gland transcriptome of the eastern diamondback rattlesnake (Crotalus adamenteous). BMC Genom. 2012, 13, 1–23. [Google Scholar] [CrossRef] [PubMed]
  84. Calvete, J.J.; Fasoli, E.; Sanz, L.; Boschetti, E.; Righetti, P.G. Exploring the Venom Proteome of the Western Diamondback Rattlesnake, Crotalus atrox, via Snake Venomics and Combinatorial Peptide Ligand Library Approaches. J. Proteome Res. 2009, 8, 3055–3067. [Google Scholar] [CrossRef] [PubMed]
  85. Segura, Á.; Herrera, M.; Reta Mares, F.; Jaime, C.; Sánchez, A.; Vargas, M.; Villalta, M.; Gómez, A.; Gutiérrez, J.M.; León, G. Proteomic, toxicological and immunogenic characterization of Mexican west-coast rattlesnake (Crotalus basiliscus) venom and its immunological relatedness with the venom of Central American rattlesnake (Crotalus simus). J. Proteom. 2017, 158, 62–72. [Google Scholar] [CrossRef] [PubMed]
  86. Durban, J.; Sanz, L.; Trevisan-Silva, D.; Neri-Castro, E.; Alagón, A.; Calvete, J.J. Integrated Venomics and Venom Gland Transcriptome Analysis of Juvenile and Adult Mexican Rattlesnakes Crotalus simus, C. tzabcan, and C. culminatus Revealed miRNA-modulated Ontogenetic Shifts. J. Proteome Res. 2017, 16, 3370–3390. [Google Scholar] [CrossRef] [PubMed]
  87. Boldrini-França, J.; Corrêa-Netto, C.; Silva, M.M.S.; Rodrigues, R.S.; De La Torre, P.; Pérez, A.; Soares, A.M.; Zingali, R.B.; Nogueira, R.A.; Rodrigues, V.M.; et al. Snake venomics and antivenomics of Crotalus durissus subspecies from Brazil: Assessment of geographic variation and its implication on snakebite management. J. Proteom. 2010, 73, 1758–1776. [Google Scholar] [CrossRef] [PubMed]
  88. Boldrini-França, J.; Rodrigues, R.S.; Fonseca, F.P.P.; Menaldo, D.L.; Ferreira, F.B.; Henrique-Silva, F.; Soares, A.M.; Hamaguchi, A.; Rodrigues, V.M.; Otaviano, A.R.; et al. Crotalus durissus collilineatus venom gland transcriptome: Analysis of gene expression profile. Biochimie 2009, 91, 586–595. [Google Scholar] [CrossRef] [PubMed]
  89. Georgieva, D.; Öhler, M.; Seifert, J.; Bergen, M.V.; Arni, R.K.; Genov, N.; Betzel, C. Snake Venomic of Crotalus durissus terrificus—Correlation with Pharmacological Activities. J. Proteome Res. 2010, 9, 2302–2316. [Google Scholar] [CrossRef] [PubMed]
  90. Rokyta, D.R.; Wray, K.P.; Margres, M.J. The genesis of an exceptionally lethal venom in the timber rattlesnake (Crotalus horridus) revealed through comparative venom-gland transcriptomics. BMC Genom. 2013, 14, 394. [Google Scholar] [CrossRef] [PubMed]
  91. Castro, E.N.; Lomonte, B.; del Carmen Gutiérrez, M.; Alagón, A.; Gutiérrez, J.M. Intraspecies variation in the venom of the rattlesnake Crotalus simus from Mexico: Different expression of crotoxin results in highly variable toxicity in the venoms of three subspecies. J. Proteom. 2013, 87, 103–121. [Google Scholar] [CrossRef] [PubMed]
  92. Calvete, J.J.; Pérez, A.; Lomonte, B.; Sánchez, E.E.; Sanz, L. Snake Venomics of Crotalus tigris: The Minimalist Toxin Arsenal of the Deadliest Neartic Rattlesnake Venom. Evolutionary Clues for Generating a Pan-Specific Antivenom against Crotalid Type II Venoms. J. Proteome Res. 2012, 11, 1382–1390. [Google Scholar] [CrossRef] [PubMed]
  93. Saviola, A.J.; Pla, D.; Sanz, L.; Castoe, T.A.; Calvete, J.J.; Mackessy, S.P. Comparative venomics of the Prairie Rattlesnake (Crotalus viridis viridis) from Colorado: Identification of a novel pattern of ontogenetic changes in venom composition and assessment of the immunoreactivity of the commercial antivenom CroFab®. J. Proteom. 2015, 121, 28–43. [Google Scholar] [CrossRef] [PubMed]
  94. Sanz, L.; Gibbs, H.L.; Mackessy, S.P.; Calvete, J.J. Venom Proteomes of Closely Related Sistrurus Rattlesnakes with Divergent Diets. J. Proteome Res. 2006, 5, 2098–2112. [Google Scholar] [CrossRef] [PubMed]
  95. Madrigal, M.; Sanz, L.; Flores-Díaz, M.; Sasa, M.; Núñez, V.; Alape-Girón, A.; Calvete, J.J. Snake venomics across genus Lachesis. Ontogenetic changes in the venom composition of Lachesis stenophrys and comparative proteomics of the venoms of adult Lachesis melanocephala and Lachesis acrochorda. J. Proteom. 2012, 77, 280–297. [Google Scholar] [CrossRef] [PubMed]
  96. Pla, D.; Sanz, L.; Molina-Sánchez, P.; Zorita, V.; Madrigal, M.; Flores-Díaz, M.; Alape-Girón, A.; Núñez, V.; Andrés, V.; Gutiérrez, J.M.; et al. Snake venomics of Lachesis muta rhombeata and genus-wide antivenomics assessment of the paraspecific immunoreactivity of two antivenoms evidence the high compositional and immunological conservation across Lachesis. J. Proteom. 2013, 89, 112–123. [Google Scholar] [CrossRef] [PubMed]
  97. Jiménez-Charris, E.; Montealegre-Sanchez, L.; Solano-Redondo, L.; Mora-Obando, D.; Camacho, E.; Castro-Herrera, F.; Fierro-Pérez, L.; Lomonte, B. Proteomic and functional analyses of the venom of Porthidium lansbergii lansbergii (Lansberg’s hognose viper) from the Atlantic Department of Colombia. J. Proteom. 2015, 114, 287–299. [Google Scholar] [CrossRef] [PubMed]
  98. Tashima, A.K.; Sanz, L.; Camargo, A.C.M.; Serrano, S.M.T.; Calvete, J.J. Snake venomics of the Brazilian pitvipers Bothrops cotiara and Bothrops fonsecai. Identification of taxonomy markers. J. Proteom. 2008, 71, 473–485. [Google Scholar] [CrossRef] [PubMed]
  99. Fry, B.G. Venomous Reptiles and their Toxins; Oxford University Press: Oxford, UK, 2015. [Google Scholar]
  100. Sanz, L.; Escolano, J.; Ferritti, M.; Biscoglio, M.J.; Rivera, E.; Crescenti, E.J.; Angulo, Y.; Lomonte, B.; Gutiérrez, J.M.; Calvete, J.J. Snake venomics of the South and Central American bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis. J. Proteom. 2008, 71, 46–60. [Google Scholar] [CrossRef] [PubMed]
  101. Doley, R.; Pahari, S.; Mackessy, S.P.; Kini, R.M. Accelerated exchange of exon segments in Viperid three-finger toxin genes (Sistrurus catenatus edwardsii; Desert massasauga). BMC Evol. Biol. 2008, 8, 196. [Google Scholar] [CrossRef] [PubMed]
  102. Shelke, R.R.J.; Sathish, S.; Gowda, T.V. Isolation and characterization of a novel postsynaptic/cytotoxic neurotoxin from Daboia russelli russelli venom. J. Pept. Res. 2002, 59, 257–263. [Google Scholar] [CrossRef] [PubMed]
  103. Skejic, J.; Hodgson, W.C. Population divergence in venom bioactivities of elapid snake Pseudonaja textilis: Role of procoagulant proteins in rapid rodent prey incapacitation. PLoS ONE 2013, 8, e63988. [Google Scholar] [CrossRef] [PubMed]
  104. Isbister, G.K. Procoagulant snake toxins: Laboratory studies, Diagnosis, and understanding snakebite coagulopathy. Semin. Thromb. Hemost. 2009, 35, 93–103. [Google Scholar] [CrossRef] [PubMed]
  105. Strickland, J.L.; Carter, S.; Kraus, F.; Parkinson, C.L. Snake evolution in Melanesia: Origin of the Hydrophiinae (Serpentes, Elapidae), and the evolutionary history of the enigmatic New Guinean elapid Toxicocalamus. Zool. J. Linn. Soc. 2016, 178, 663–678. [Google Scholar] [CrossRef]
  106. Sanders, K.L.; Lee, M.S.Y.; Leys, R.; Foster, R.; Scott Keogh, J. Molecular phylogeny and divergence dates for Australasian elapids and sea snakes (hydrophiinae): Evidence from seven genes for rapid evolutionary radiations. J. Evol. Biol. 2008, 21, 682–695. [Google Scholar] [CrossRef] [PubMed]
  107. Scanlon, J.D.; Lee, M.S.Y. Phylogeny of Australasian venomous snakes (Colubroidea, Elapidae, Hydrophiinae) based on phenotypic and molecular evidence. Zool. Scr. 2004, 33, 335–366. [Google Scholar] [CrossRef]
  108. Lukoschek, V.; Keogh, J.S. Molecular phylogeny of sea snakes reveals a rapidly diverged adaptive radiation. Biol. J. Linn. Soc. 2006, 89, 523–539. [Google Scholar] [CrossRef]
  109. Sanders, K.L.; Lee, M.S.Y.; Mumpuni; Bertozzi, T.; Rasmussen, A.R. Multilocus phylogeny and recent rapid radiation of the viviparous sea snakes (Elapidae: Hydrophiinae). Mol. Phylogenet. Evol. 2013, 66, 575–591. [Google Scholar] [CrossRef] [PubMed]
  110. Maduwage, K.; O’Leary, M.A.; Isbister, G.K. Diagnosis of snake envenomation using a simple phospholipase A2 assay. Sci. Rep. 2014, 4, 4827. [Google Scholar] [CrossRef] [PubMed]
  111. Wagstaff, S.C.; Laing, G.D.; David, R.; Theakston, G.; Papaspyridis, C.; Harrison, R.A.; Theakston, R.D.G. Bioinformatics and multiepitope DNA immunization to design rational snake antivenom. PLoS Med. 2006, 3, e184. [Google Scholar] [CrossRef] [PubMed]
  112. Silva, A.; Hodgson, W.C.; Isbister, G.K. Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms. Toxins 2016, 8, 302. [Google Scholar] [CrossRef] [PubMed]
  113. Isbister, G.K.; Maduwage, K.; Page, C.B. Antivenom cross neutralisation in a suspected Asian pit viper envenoming causing severe coagulopathy. Toxicon 2014, 90, 286–290. [Google Scholar] [CrossRef] [PubMed]
  114. Torres, A.M.; Wong, H.Y.; Desai, M.; Moochhala, S.; Kuchel, P.W.; Kini, R.M. Identification of a Novel Family of Proteins in Snake Venoms. Purification And Structural Characterization Of Nawaprin From Naja Nigricollis Snake Venom. J. Biol. Chem. 2003, 278, 40097–40104. [Google Scholar] [CrossRef] [PubMed]
  115. Fry, B.G. 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 Res. 2005, 15, 403–420. [Google Scholar] [CrossRef] [PubMed]
  116. Chen, X.; Huang, S.; Guo, P.; Colli, G.R.; Nieto Montes de Oca, A.; Vitt, L.J.; Pyron, R.A.; Burbrink, F.T. Understanding the formation of ancient intertropical disjunct distributions using Asian and Neotropical hinged-teeth snakes (Sibynophis and Scaphiodontophis: Serpentes: Colubridae). Mol. Phylogenet. Evol. 2013, 66, 254–261. [Google Scholar] [CrossRef] [PubMed]
  117. Esselstyn, J.A.; Brown, R.M. The role of repeated sea-level fluctuations in the generation of shrew (Soricidae: Crocidura) diversity in the Philippine Archipelago. Mol. Phylogenet. Evol. 2009, 53, 171–181. [Google Scholar] [CrossRef] [PubMed]
  118. Catullo, R.A.; Scott Keogh, J. Aridification drove repeated episodes of diversification between Australian biomes: Evidence from a multi-locus phylogeny of Australian toadlets (Uperoleia: Myobatrachidae). Mol. Phylogenet. Evol. 2014, 79, 106–117. [Google Scholar] [CrossRef] [PubMed]
  119. Menegon, M.; Loader, S.P.; Marsden, S.J.; Branch, W.R.; Davenport, T.R.B.; Ursenbacher, S. The genus Atheris (Serpentes: Viperidae) in East Africa: Phylogeny and the role of rifting and climate in shaping the current pattern of species diversity. Mol. Phylogenet. Evol. 2014, 79, 12–22. [Google Scholar] [CrossRef] [PubMed]
  120. Keogh, J.S.; Scott, I.A.W.; Hayes, C. Rapid And Repeated Origin of Insular Gigantism and Dwarfism in Australian Tiger Snakes. Evolution 2005, 59, 226–233. [Google Scholar] [CrossRef] [PubMed]
  121. Williams, V.; White, J. Variation in venom constituents within a single isolated population of peninsula tiger snake (Notechis ater niger). Toxicon 1987, 25, 1240–1243. [Google Scholar] [CrossRef]
  122. Li, M.; Fry, B.G.; Kini, R. Eggs-Only Diet: Its Implications for the Toxin Profile Changes and Ecology of the Marbled Sea Snake (Aipysurus eydouxii). J. Mol. Evol. 2005, 60, 81–89. [Google Scholar] [CrossRef] [PubMed]
  123. Shine, R. Ecology of Highly Venomous Snakes: The Australian Genus Oxyuranus (Elapidae). J. Herpetol. 1983, 17, 60–69. [Google Scholar] [CrossRef]
  124. Harvey, A.L. Twenty years of dendrotoxins. Toxicon 2001, 39, 15–26. [Google Scholar] [CrossRef]
  125. Kornhauser, R.; Hart, A.J.; Reeve, S.; Smith, A.I.; Fry, B.G.; Hodgson, W.C. Variations in the pharmacological profile of post-synaptic neurotoxins isolated from the venoms of the Papuan (Oxyuranus scutellatus canni) and coastal (Oxyuranus scutellatus scutellatus) taipans. NeuroToxicol. 2010, 31, 239–243. [Google Scholar] [CrossRef] [PubMed]
  126. Kuruppu, S.; Reeve, S.; Banerjee, Y.; Kini, R.M.; Smith, A.I.; Hodgson, W.C. Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni). J. Pharmacol. Exp. Ther. 2005, 315, 1196–1202. [Google Scholar] [CrossRef] [PubMed]
  127. Petras, D.; Heiss, P.; Harrison, R.A.; Süssmuth, R.D.; Calvete, J.J. Top-down venomics of the East African green mamba, Dendroaspis angusticeps, and the black mamba, Dendroaspis polylepis, highlight the complexity of their toxin arsenals. J. Proteom. 2016, 146, 148–164. [Google Scholar] [CrossRef] [PubMed]
  128. Gibbs, H.L.; Sanz, L.; Sovic, M.G.; Calvete, J.J. Phylogeny-Based Comparative Analysis of Venom Proteome Variation in a Clade of Rattlesnakes (Sistrurus sp.). PLoS ONE 2013, 8, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  129. Jorge da Silva, N., Jr.; Aird, S.D. Prey specificity, comparative lethality and compositional differences of coral snake venoms. Comp. Biochem. Physiol. Part C Toxicol. Pharmacol. 2001, 128, 425–456. [Google Scholar] [CrossRef]
  130. Gibbs, H.L.; Mackessy, S.P. Functional basis of a molecular adaptation: Prey-specific toxic effects of venom from Sistrurus rattlesnakes. Toxicon 2009, 53, 672–679. [Google Scholar] [CrossRef] [PubMed]
  131. Starkov, V.G.; Osipov, A.V.; Utkin, Y.N. Toxicity of venoms from vipers of Pelias group to crickets Gryllus assimilis and its relation to snake entomophagy. Toxicon 2007, 49, 995–1001. [Google Scholar] [CrossRef] [PubMed]
  132. Barlow, A.; Pook, C.E.; Harrison, R.A.; Wüster, W. Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution. Proc. R. Soc. Lond. B Biol. Sci. 2009, 276, 2443–2449. [Google Scholar] [CrossRef] [PubMed]
  133. Daltry, J.C.; Wuster, W.; Thorpe, R.S. Diet and snake venom evolution. Nature 1996, 379, 537. [Google Scholar] [CrossRef] [PubMed]
  134. Poran, N.S.; Coss, R.G.; Benjamini, E. Resistance of California ground squirrels (Spermophilus beecheyi) to the venom of the northern Pacific rattlesnake (Crotalus viridis oreganus): A study of adaptive variation. Toxicon 1987, 25, 767–777. [Google Scholar] [CrossRef]
  135. Heatwole, H.; Poran, N.S. Resistances of Sympatric and Allopatric Eels to Sea Snake Venoms. Copeia 1995, 1995, 136–147. [Google Scholar] [CrossRef]
  136. Dowell, N.L.; Giorgianni, M.W.; Kassner, V.A.; Selegue, J.E.; Sanchez, E.E.; Carroll, S.B. The Deep Origin and Recent Loss of Venom Toxin Genes in Rattlesnakes. Curr. Biol. 2016, 26, 2434–2445. [Google Scholar] [CrossRef] [PubMed]
  137. Hargreaves, A.D.; Swain, M.T.; Hegarty, M.J.; Logan, D.W.; Mulley, J.F. Restriction and Recruitment—Gene Duplication and the Origin and Evolution of Snake Venom Toxins. Genome Biol. Evol. 2014, 6, 2088–2095. [Google Scholar] [CrossRef] [PubMed]
  138. Casewell, N.R.; Wagstaff, S.C.; Harrison, R.A.; Renjifo, C.; Wüster, W. Domain Loss Facilitates Accelerated Evolution and Neofunctionalization of Duplicate Snake Venom Metalloproteinase Toxin Genes. Mol. Biol. Evol. 2011, 28, 2637–2649. [Google Scholar] [CrossRef] [PubMed]
  139. Lynch, V.J. Inventing an arsenal: Adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes. BMC Evol. Biol. 2007, 7, 1–14. [Google Scholar] [CrossRef] [PubMed]
  140. Doley, R.; Mackessy, S.P.; Kini, R. Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins. BMC Evol. Biol. 2009, 9, 146–159. [Google Scholar] [CrossRef] [PubMed]
  141. Gibbs, H.L.; Sanz, L.; Chiucchi, J.E.; Farrell, T.M.; Calvete, J.J. Proteomic analysis of ontogenetic and diet-related changes in venom composition of juvenile and adult Dusky Pigmy rattlesnakes (Sistrurus miliarius barbouri). J. Proteom. 2011, 74, 2169–2179. [Google Scholar] [CrossRef] [PubMed]
  142. Andrade, D.V.; Abe, A.S. Relationship of Venom Ontogeny and Diet in Bothrops. Herpetologica 1999, 55, 200–204. [Google Scholar]
  143. Saldarriaga, M.M.; Otero, R.; Núñez, V.; Toro, M.F.; Díaz, A.; Gutiérrez, J.M. Ontogenetic variability of Bothrops atrox, and Bothrops asper snake venoms from Colombia. Toxicon 2003, 42, 405–411. [Google Scholar] [CrossRef]
  144. Mackessy, S.P. Venom ontogeny in the Pacific rattlesnakes Crotalus viridis helleri and Crotalus viridis oreganus. In Copeia; American Society of Ichthyologists and Herpetologists (ASIH): Lawrence, KS, USA, 1988. [Google Scholar] [CrossRef]
  145. Zelanis, A.; Tashima, A.K.; Rocha, M.M.T.; Furtado, M.F.; Camargo, A.C.M.; Ho, P.L.; Serrano, S.M.T. Analysis of the Ontogenetic Variation in the Venom Proteome/Peptidome of Bothrops jararaca Reveals Different Strategies to Deal with Prey. J. Proteome Res. 2010, 9, 2278–2291. [Google Scholar] [CrossRef] [PubMed]
  146. Tan, N.H.; Armugam, A.; Mirtschin, P.J. The biological properties of venoms from juvenile and adult taipan (Oxyuranus scutellatus) snakes. Comp. Biochem. Physiol. B 1992, 103, 585–588. [Google Scholar] [CrossRef]
  147. Tan, N.H.; Ponnudurai, G.; Mirtschin, P.J. A comparative study of the biological properties of venoms from juvenile and adult inland taipan (Oxyuranus microlepidotus) snake venoms. Toxicon 1993, 31, 363–367. [Google Scholar] [CrossRef]
  148. Castoe, T.A.; Daza, J.M.; Smith, E.N.; Sasa, M.M.; Kuch, U.; Campbell, J.A.; Chippindale, P.T.; Parkinson, C.L. Comparative phylogeography of pitvipers suggests a consensus of ancient Middle American highland biogeography. J. Biogeogr. 2009, 36, 88–103. [Google Scholar] [CrossRef]
  149. Daza, J.M.; Castoe, T.A.; Parkinson, C.L. Using regional comparative phylogeographic data from snake lineages to infer historical processes in Middle America. Ecography 2010, 33, 343–354. [Google Scholar] [CrossRef]
  150. Wittenberg, R.D.; Jadin, R.C.; Fenwick, A.M.; Gutberlet, R.L. Recovering the evolutionary history of Africa’s most diverse viper genus: Morphological and molecular phylogeny of Bitis (Reptilia: Squamata: Viperidae). Org. Divers. Evol. 2015, 15, 115–125. [Google Scholar] [CrossRef]
  151. Pyron, R.A.; Burbrink, F.T.; Colli, G.R.; de Oca, A.N.M.; Vitt, L.J.; Kuczynski, C.A.; Wiens, J.J. The phylogeny of advanced snakes (Colubroidea), with discovery of a new subfamily and comparison of support methods for likelihood trees. Mol. Phylogenet. Evol. 2011, 58, 329–342. [Google Scholar] [CrossRef] [PubMed]
  152. Lee, M.S.Y.; Sanders, K.L.; King, B.; Palci, A. Diversification rates and phenotypic evolution in venomous snakes (Elapidae). R. Soc. Open Sci. 2016, 3, 150277. [Google Scholar] [CrossRef] [PubMed]
  153. Malhotra, A.; Thorpe, R.S. A phylogeny of four mitochondrial gene regions suggests a revised taxonomy for Asian pitvipers (Trimeresurus and Ovophis). Mol. Phylogenet. Evol. 2004, 32, 83–100. [Google Scholar] [CrossRef] [PubMed]
Figure 1. The relative proportions of different protein families for the venoms of: elapids (upper); viperines (middle); and crotalines (lower), averaged from the number of species noted in the brackets. PLA2, phospholipase A2; SVSP, snake venom serine protease; SVMP, snake venom metalloprotease; LAAO, l-amino acid oxidase; 3FTx, three-finger toxin; KUN, kunitz peptide; CRiSP, cysteine-rich secretory protein; CTL, C-type lectin; DIS, disintegrin; NP, natriuretic peptide; NGF, nerve growth factor; CYS, cystatin; VEGF, vascular endothelial growth factor; MVC, minor venom component.
Figure 1. The relative proportions of different protein families for the venoms of: elapids (upper); viperines (middle); and crotalines (lower), averaged from the number of species noted in the brackets. PLA2, phospholipase A2; SVSP, snake venom serine protease; SVMP, snake venom metalloprotease; LAAO, l-amino acid oxidase; 3FTx, three-finger toxin; KUN, kunitz peptide; CRiSP, cysteine-rich secretory protein; CTL, C-type lectin; DIS, disintegrin; NP, natriuretic peptide; NGF, nerve growth factor; CYS, cystatin; VEGF, vascular endothelial growth factor; MVC, minor venom component.
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Figure 2. Differences in the venom composition among the family elapidae, averaged from the number of species noted in the brackets. The 3FTx/PLA2 dichotomy is shown for New World coral snakes (upper pair), Australian elapids (middle pair) and Afro-Asian cobras and kraits (lower pair). The lowermost pie chart shows the unique venom composition of African black mamba. PLA2, phospholipase A2; SVSP, snake venom serine protease; SVMP, snake venom metalloprotease; LAAO, l-amino acid oxidase; 3FTx, three-finger toxin; KUN, kunitz peptide; CRiSP, cysteine-rich secretory protein; NP, natriuretic peptide; VEGF, vascular endothelial growth factor; NGF, nerve growth factor; MVC, minor venom component. Mildly venomous Australian species: Drysdalia coronoides, Austrelaps labialis and Toxicocalamus longissimus. Medically significant Australian elapids: Oxyuranus scutellatus, Notechis scutatus, Pseudechis papuanus and Micropechis ikaheka.
Figure 2. Differences in the venom composition among the family elapidae, averaged from the number of species noted in the brackets. The 3FTx/PLA2 dichotomy is shown for New World coral snakes (upper pair), Australian elapids (middle pair) and Afro-Asian cobras and kraits (lower pair). The lowermost pie chart shows the unique venom composition of African black mamba. PLA2, phospholipase A2; SVSP, snake venom serine protease; SVMP, snake venom metalloprotease; LAAO, l-amino acid oxidase; 3FTx, three-finger toxin; KUN, kunitz peptide; CRiSP, cysteine-rich secretory protein; NP, natriuretic peptide; VEGF, vascular endothelial growth factor; NGF, nerve growth factor; MVC, minor venom component. Mildly venomous Australian species: Drysdalia coronoides, Austrelaps labialis and Toxicocalamus longissimus. Medically significant Australian elapids: Oxyuranus scutellatus, Notechis scutatus, Pseudechis papuanus and Micropechis ikaheka.
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Figure 3. Differences in venom composition in different genera of viperids, showing the less extreme variation in individual protein families compared to elapids. The majority of the venoms are made up of SVMP, PLA2 and SVSP. Differences include the presence of KUNs in viperines and the greater importance of NPs in some crotalines. Abbreviations: SVMP, snake venom metalloprotease; PLA2, phospholipase A2; SVSP, snake venom serine protease; LAAO, l-amino acid oxidase; CRiSP, cysteine rich secretory protein; CTL, C-type lectin/snaclec; DIS, disintegrin; NP, natriuretic peptide; VEGF, vascular endothelial growth factor; MVC, minor venom components.
Figure 3. Differences in venom composition in different genera of viperids, showing the less extreme variation in individual protein families compared to elapids. The majority of the venoms are made up of SVMP, PLA2 and SVSP. Differences include the presence of KUNs in viperines and the greater importance of NPs in some crotalines. Abbreviations: SVMP, snake venom metalloprotease; PLA2, phospholipase A2; SVSP, snake venom serine protease; LAAO, l-amino acid oxidase; CRiSP, cysteine rich secretory protein; CTL, C-type lectin/snaclec; DIS, disintegrin; NP, natriuretic peptide; VEGF, vascular endothelial growth factor; MVC, minor venom components.
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Figure 4. African black mamba Dendroaspis polylepis (left) and Australian coastal taipan Oxyuranus scutellatus (right): These elapids represent evolutionary parallels on different continents in terms of their morphology, ecology and biology, but the pharmacological effects caused by their venoms are the result of different protein families. Some of these protein families have convergently evolved to cause potent neurotoxicity. Photo credits: Nick Evans (black mamba), and Brendan Schembri (coastal taipan).
Figure 4. African black mamba Dendroaspis polylepis (left) and Australian coastal taipan Oxyuranus scutellatus (right): These elapids represent evolutionary parallels on different continents in terms of their morphology, ecology and biology, but the pharmacological effects caused by their venoms are the result of different protein families. Some of these protein families have convergently evolved to cause potent neurotoxicity. Photo credits: Nick Evans (black mamba), and Brendan Schembri (coastal taipan).
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Table 1. The 42 elapids included in the study (excluding two aberrant species), with the proportion of each of the eight major protein families in venom (expressed as percent of total venom), which make up 80–100% of their venom proteome.
Table 1. The 42 elapids included in the study (excluding two aberrant species), with the proportion of each of the eight major protein families in venom (expressed as percent of total venom), which make up 80–100% of their venom proteome.
SPECIESPLA2SVSPSVMPLAAO3FTKUNCRiSPNP%WV3FT + PLA2REF
Austrelaps labialis33 3 4598 9878[3]
Drysdalia coronoides 86.49.22.8 98.486.4[4]
Micropechis ikaheka80<0.17.60.49.20.71.8 99.889.2[5]
Notechis scutatus74.55.9 5.66.90.3293.280.1[6]
Oxyuranus scutellatus68–80<55–9 0–9<10<11>9068–89[7]
Pseudechis papuanus90.2 2.81.63.1 2.3 10093.3[8]
Toxicocalamus longissimus6.5 1.4 92.1 10098.6[9]
Aipysurus laevis71.2 25.3 2.5 9996.5[10]
Hydrophis cyanocinctus18.9 81.1 100100[9]
H. platurus32.9 0.9 49.9 9.1 92.882.8[11]
H. schistosus27.5 0.50.270.5 1.3 10098[12]
Laticauda colubrina33.3 66.1 0.05 99.4599.4[13]
Bungarus caeruleus (Sri Lanka)64.5 1.3 194.45.5 94.783.5[14]
B. candidus Malaya25.23.94.95.830.112.63.9186.455.6[15]
B. fasciatus Vietnam66.8 3.571.31.80.4 80.868.1[16]
B.fasciatus Malaya44.25.84.75.817.49.31.2 88.461.6[15]
Dendroaspis angusticeps 6.7 69.216.32 94.269.2[17]
D. polylepis 3.2 3161.1 2.995.331[18]
Naja haje4 91601.910 85.964[19]
N. melanoleuca12.9 9.7 57.13.87.6 91.170[20]
N. katiensis29 3.3 67.1 0.2 99.696.1[21]
N. mossambica27.1 2.6 69.3 9996.4[21]
N. nigricollis21.9 2.4 73.2 0.2 97.795.1[21]
N. nubiae26.4 2.6 70.9 99.997.3[21]
N. pallida30.1 1.6 67.7 99.497.8[21]
N. atra China12.2 1.6 84.3 1.8 99.996.5[22]
Naja atra Taiwan14–17 2–2.60.276–80 2.2–2.4 >9390–97[23]
N. kaouthia China26.9 1.1 56.6 5.4 9083.5[24]
Naja kaouthia Malaya23.5 3.31.163.70.54.3 96.487.2[25]
Naja kaouthia Thailand12.2 2.6178.3 2.30.296.490.5[25]
Naja kaouthia Vietnam17.4 1.60.576.4 0.8 96.793.8[25]
N. naja Eastern India11.40.310.863.80.42.1279.875.2[26]
Naja naja North-west India21.4 0.9 74 2.5 98.895.4[27]
Naja naja Sri Lanka14 0.9 80.5 3.7 99.194.5[27]
N. sputatrix31.20.41.30.164.20.2 9795.4[28]
Ophiophagus hannah2.8 11.90.564.53.36.50.289.567.3[29]
Micrurus alleni10.9 1.2377.3 92.488.2[30]
M. altirostris13.7 0.91.279.52.10.1 97.593.2[31]
M. clarki36.511.63.848.20.9 9284.7[32]
M. corallinus11.90.82.92.381.7 99.693.6[31]
M. dumerelii521.91.83.128.19 95.980.1[33]
M. fulvius64.9 2.9 25.12.2 95.190[34]
M. mipartitus291.31.6461.11.9 98.990.1[35]
M. mosquitensis55.60.52.62.822.59.8 93.878.1[30]
M. multifasciatus8.2 3.63.2831.9 99.991.2[35]
M. nigrocinctus480.74.32.338 93.386[36]
M. tschudii4.1 0.795.21.6 10099.3[37]
Abbreviations: PLA2, phospholipase A2; SVSP, snake venom serine protease; SVMP, snake venom metalloprotease; LAAO, l-amino acid oxidase; 3FT, three-finger toxin; KUN, Kunitz peptides; CRiSP, Cysteine-Rich Secretory Protein; %WV, percentage of venom; 3FT + PLA2, percentage of whole venom made up of these two protein families.
Table 2. The 20 viperines (true vipers) included in the study with the proportion of the 11 major protein families in each venom (expressed as percent of total venom), which make up 90–100% of their venom proteome (except *, venom proteome incompletely characterized).
Table 2. The 20 viperines (true vipers) included in the study with the proportion of the 11 major protein families in each venom (expressed as percent of total venom), which make up 90–100% of their venom proteome (except *, venom proteome incompletely characterized).
SPECIESPLA2SVSPSVMPLAAOCRiSPCTL/SNACLECDISNPKUNVEGFCYS%WVREF
Bitis arietans4.319.538.5 13.217.8 4.2 1.799.2[38]
B.caudalis59.815.111.51.71.24.92.3 3.2 99.7[38]
B.gabonica11.426.422.91.3214.33.42.8319.898.3[38]
B.nasicornis20.121.940.93.21.34.23.5 4.299.3[38]
B.rhinoceros4.823.930.82.21.214.18.50.37.5 5.398.6[38]
Cerastes cerastes (Morocco)19.16.963.1 0.71.78.5 100[39]
C. cerastes (Tunisia)16.613.255.96.2 3.24.9 100[39]
Daboia russelii (Pakistan)32.83.221.80.62.66.40.4 28.41.5 97.7[40]
D. russelii (West India)32.5824.80.36.81.84.9 12.51.8 93.4[41]
D. russelii (Sri Lanka)35166.95.2222.4 4.6 92.1[42]
Echis carinatus sochureki7.974.5856.571.191.9916.537.7 0.4 97[43]
E. coloratus5.73.5861.413.915.699.455.8 0.32 96[43]
E. ocellatus8.51.7172.431.360.346.46 2.72 93.5[43]
E. pyramidium leakeyi21.571.4248.942.83 24.26 0.28 99.3[43]
Macrovipera lebetina (Tunisia)55.563.1 3.215.1 3.13.3 98.3[44]
M. l. obtusa14.614.932.11.72.614.811.35.3 97.3[45]
M. mauritanica5.58.345.4 8.113.84.52.54.9 93[44]
Vipera anatolica8.11.641.5 15.91.12 0.3 70.5 *[46]
V. berus103119282111 84 *[47]
V. kaznakovi411116410120.53 4 94.5[48]
V. nikolskii65190.660.080.664 8 97.4[48]
V. orlovi242415512110.56 0.154 91.7[48]
V. raddei23.88.431.60.27.49.69.760.92.4 100[45]
V. renardii4481248313 0.83 95.8[48]
Abbreviations: PLA2, phospholipase A2; SVSP, snake venom serine protease; SVMP, snake venom metalloprotease; LAAO, l-amino acid oxidase; CRiSP, Cysteine-Rich Secretory Protein; CTL/SNACLEC, C-type lectins and C-type lectin like; DIS, disintegrin; NP, natriuretic peptides including vasoactive peptides; bradykinin potentiating and inhibitory peptides; KUN, kunitz peptides; VEGF, vascular endothelial growth factor; CYS, cystatin; %WV, percentage of whole venom.
Table 3. The 65 crotalines (pit vipers) included in the study (excluding one aberrant species), with the proportion of the ten major protein families in each venom (expressed as percent of total venom), which make up 80–100% of their venom proteome. Taxonomy follows Fenwick et al. 2009 [49].
Table 3. The 65 crotalines (pit vipers) included in the study (excluding one aberrant species), with the proportion of the ten major protein families in each venom (expressed as percent of total venom), which make up 80–100% of their venom proteome. Taxonomy follows Fenwick et al. 2009 [49].
SPECIESPLA2SVSPSVMPLAAOCRiSPCTL/SNACLECDISNPDEFMPi%WVREF
Calloselasma rhodostoma4.414.941.272.526.3 96.3[50]
Cryptelytrops purpureomaculatus8123510619 2 92[51]
Gloydius brevicaudus253.764.40.91.10.24.6 99.9[52]
G. intermedius9.936.22.613.16.20.8 25.3 94.1[53]
Ovophis okinavensis0.6593.14.20.62 0.47 99[54]
Protobothrops elegans77.110.480.50.10.2 96.3[55]
Protobothrops flavoviridis55.511.817.33.120.9 2.6 93.2[56]
P.mucrosquamatus22.510.44320.83.90.83.6 87[57]
Viridovipera stejnegeri24.51143.13.361.52.21.2 92.8[57]
Agkistrodon bilineatus (3 subsp)34.3–427.6–16.924.5–30.82.6–4.90–5.60.4–1.42.2–3.14.6–8.7 76.7+[58]
A. c. contortrix50.75.8525420.8 88.35[59]
A. piscivorus (3 subsp)33.6–4610.1–13.921–33.10.8–4.52–3.50.8–3.22.2–4.95.7–5.9 76.2[58]
Atropoides nummifer36.52218.29.11.91.32.58.6 100[60]
A. picadoi9.513.566.42.24.81.8<0.11.8 100[60]
Bothriechis aurifer 7.335.19.510.716.41.413.4 3.297[61]
B. bicolor35.219.18.510.814.47.63.6 4.694.8[61]
B. marchi14.310.134.21.12.84.26.510.6 8.583.8[61]
B. lateralis8.711.355.16.16.5 11.1 98.8[61]
B. nigroviridis38.318.4 0.52.1 37 96.3[62]
B. schlegelii43.85.817.78.92.1 13.4 91.7[61]
B. supraciliaris13.415.26.85.94.3 1.621.9 69.1[63]
B. thalassinus 12.139.64.35.111.5210.6 9.995.1[61]
Bothrocophias campbelli43.121.315.85.70.96.40.33.9 97.4[64]
B. colombiensis44.3<142.15.70.1 5.60.8 99.5[65]
Bothropoides diporus24.17.234.27.4 2.91.415.9 2.695.7[66]
B. erythromelaus (5 populations)10.1–15.14–9.732.5–59.9 0.48.4–21.63.4–8.99.3–14.5 68+[67]
B. insularis1012.5301.31.331.3 11.3 97.7[68]
B. jaracara (south-east)3.713.735.67.22.49.6716.4 95.6[69]
B. jaracara (south)20.228.610.382.69.40.222.6 100[69]
B. neuwiedi8.48.849.916.728.6 94.4 [70]
B. pauloensis31.910.538.12.82.20.61.312.4 99.8[71]
Bothrops asper (Caribbean coast)28.818.2419.20.10.52.1 99.9[72]
B. asper (Pacific coast)45.54.4444.60.10.51.4 100[72]
B. atrox (Western Para Brazil)5.7–7.59.7–14.146.5–548.7–9.43.7–4.310.2–13.1 84.5+[73]
B. atrox (Colombia)24.110.948.54.72.67.11.70.3 99.9[74]
B. atrox (Venezuela)7.7–8.52.3851.2–1.52.8–3.8 99+[75]
B. atrox (Peru)1111.158.210.52.43.63.2 100[76]
B. ayerbi0.79.353.73.31.110.12.38.3 88.8[77]
B. barnetti6.46.774.10.83.13.35.5 99.9[76]
B. caribbaeus12.84.768.68.42.6 1.7 98.8 [78]
B. jararacussu25.712.326.2152.29.7 91.1[70]
B. lanceolatus8.614.474.22.8 <0.1 100[78]
B. pictus14.17.768 1.18.9 99.8[76]
B. pirajai40.27.120.75.2 9.21.45.6 89.4[79]
B. punctatus9.35.441.53.11.216.73.810.7 91.7[80]
Cerrophidion godmani23.419.132.854.20.57.55.7 98.2[81]
C. sasai23.419.132.854.20.57.55.7 98.2[82]
Crotalus adamanteus7.82024.45.31.322.2 16.8 97.8[83]
C. atrox7.319.849.784.33.46.23 100[84]
C. basiliscus141168 2 499[85]
C. culminatus8.310.135.52.71.913 1.624.4 97.5[86]
C. durissus cascavella90.91.2<0.1<0.10.9<0.10.2 93.4[87]
C. d. collilineatus721.90.40.51.8<0.10.5 20.8 98[88]
C. d. terrificus48.525.33.9 77.7[89]
C. horridus22.858.20.11.10.80.22 0.2 82.3[90]
C. simus simus22.430.427.45.710.61.56.5 95.5[91]
C. tigris 26.866.2 1.9 0.2 95.1[92]
C. tzabacan11.15.418.50.5 35.2 4.223.5 98.4[86]
C. viridis7.7–10.226.810.9–11.41.9–2.52.1–3.91.8–3.30.16.5–8.235.6–380.193.5+[93]
Sistrurus catenatus (3 subsp.)31.3-31.918.2-24.440.6-48.61.6-4.20.8-10.7 0.9-4.2 93.4+[94]
S. miliarius32.517.136.12.12.9 7.7 98.4[94]
Lachesis acrochorda2.335.123.29.60.96.9 21.5 99.5[95]
L. melanocephala13.42118.93.6 7.5 30.2 94.6[94]
L. muta muta8.731.231.92.71.87.9 14.7 98.9[94]
L. m. rhombeata10.826.529.50.51.42.7 28 99.4[96]
L. stenophrys14.121.230.62.7 3.6 27.1 99.3[94]
Porthidium lansbergii16.24.535.53.61.46.712.912.4 93.2[97]
P. nasutum11.69.652.131.310.49.91.9 99.8[81]
P. ophryomegus13.57.3453.30.6816.74.2 98.6[97]
Rhinocerophis alternatus25.852.214.92.514.8 92.2[70]
R. cotiara0.6135119.62.94.7 91.8[70]
R. fonescai30.14.142.51.92.49.84.4 95.2[98]
Abbreviations: PLA2, phospholipase A2; SVSP, snake venom serine protease; SVMP, snake venom metalloprotease; LAAO, l-amino acid oxidase; CRiSP, Cysteine-Rich Secretory Protein; CTL/SNACLEC, C-type lectins and C-type lectin like; DIS, disintegrin; NP, natriuretic peptides, including vasoactive peptides, bradykinin potentiating and inhibitory peptides; DEF, defensin (crotamine); MPi, snake venom metalloprotease inhibitor; %WV, percentage of whole venom.

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Tasoulis, T.; Isbister, G.K. A Review and Database of Snake Venom Proteomes. Toxins 2017, 9, 290. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins9090290

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Tasoulis T, Isbister GK. A Review and Database of Snake Venom Proteomes. Toxins. 2017; 9(9):290. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins9090290

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Tasoulis, Theo, and Geoffrey K. Isbister. 2017. "A Review and Database of Snake Venom Proteomes" Toxins 9, no. 9: 290. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins9090290

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