Electric Blue: Molecular Evolution of Three-Finger Toxins in the Long-Glanded Coral Snake Species Calliophis bivirgatus

Abstract

The genus Calliophis is the most basal branch of the family Elapidae and several species in it have developed highly elongated venom glands. Recent research has shown that C. bivirgatus has evolved a seemingly unique toxin (calliotoxin) that produces spastic paralysis in their prey by acting on the voltage-gated sodium (NaV) channels. We assembled a transcriptome from C. bivirgatus to investigate the molecular characteristics of these toxins and the venom as a whole. We find strong confirmation that this genus produces the classic elapid eight-cysteine three-finger toxins, that δδ-elapitoxins (toxins that resemble calliotoxin) are responsible for a substantial portion of the venom composition, and that these toxins form a distinct clade within a larger, more diverse clade of C. bivirgatus three-finger toxins. This broader clade of C. bivirgatus toxins also contains the previously named maticotoxins and is somewhat closely related to cytotoxins from other elapids. However, the toxins from this clade that have been characterized are not themselves cytotoxic. No other toxins show clear relationships to toxins of known function from other species.

De novo venom gland transcriptomics of Calliophis bivirgata flaviceps: uncovering the complexity of toxins from the Malayan blue coral snake

“…These are non-enzymatic polypeptides with molecular weights of approximately 6-9 kDa, orientated in three beta-stranded loops that resemble three protruding fingers [ 50 , 51 ]. Comparison of the venom gland transcriptomic profiles between the current study and a recent report [ 17 ] reveals a similar dominating pattern of 3FTx, notwithstanding variation in the relative proportions of many toxin subtypes ( Table 3 ). The variation implies potential inter-individual differences between the specimens, e.g., wild versus captive snakes from different geographical regions, or extensive post-translational modifications [ 52 ].…”

“…In the venom gland transcriptome, Cb_FTX01 and Cb_FTX02 were the two most abundantly expressed transcripts of S-3FTx. Both transcripts were annotated as calliotoxins (UniProtKB: P0DL82 and Cbivi_3FTx_034 reported by Dashevsky et al [ 17 ]), which is by far the only delta-neurotoxin discovered from snake venoms [ 10 ]. To elucidate variation in the genes, sequences of Cb_FTX01 and Cb_FTX02 were further compared with calliotoxins and representative alpha-neurotoxins from common elapid species found in Southeast Asia ( Figure 4 ).…”

“…A recent proteomic study showed that Malaysian C. bivirgata flaviceps venom contains high amounts of cytotoxin-like proteins (22.6%) and phospholipases A 2 (41.1%) which could be instrumental in the pathophysiology of envenomation [ 15 ]. Other studies further detected a sodium channel antagonist, a delta-neurotoxin called calliotoxin in C. bivirgata venom, indicating that C. bivirgata envenomation can potentially result in neurotoxicity [ 10 , 17 ]. The C. bivirgata venom, however, showed negligible immunological cross-reactivity with various elapid antivenoms that were raised against non-coral snake species in Asia, despite having abundant three-finger toxins and phospholipases A 2 as the venoms of most other elapid species [ 18 ].…”

“…To better understand the diversity and functions of its toxins, this study investigated the de novo venom gland transcriptome of C. bivirgata flaviceps (a subspecies from Peninsular Malaysia) through a high-throughput next-generation sequencing approach and deep data mining. In addition, the findings were compared to a recent study of three-finger toxin evolution in this species which also employed the venom gland transcriptomic method [ 17 ]. Uncovering the complexity and the diversity of toxin genes in this unique species enriches our current knowledge base of snake venoms, and provides deeper insights into the clinical, biomedical, and evolutionary significance of the Asiatic coral snakes [ 19 ].…”

Animal Venoms and Their Components: Molecular Mechanisms of Action

“…One paper focuses on the molecular evolution of three-finger toxins (3FTX) in the snake genus Calliophis, which is the most basal branch of the family Elapidae [5]. It is shown that this genus produces the classic elapid eight-cysteine 3FTXs, which form several different clades.…”