Conotoxin Diversity in Chelyconus ermineus (Born, 1778) and the Convergent Origin of Piscivory in the Atlantic and Indo-Pacific Cones

Abstract

The transcriptome of the venom duct of the Atlantic piscivorous cone species Chelyconus ermineus (Born, 1778) was determined. The venom repertoire of this species includes at least 378 conotoxin precursors, which could be ascribed to 33 known and 22 new (unassigned) protein superfamilies, respectively. Most abundant superfamilies were T, W, O1, M, O2, and Z, accounting for 57% of all detected diversity. A total of three individuals were sequenced showing considerable intraspecific variation: each individual had many exclusive conotoxin precursors, and only 20% of all inferred mature peptides were common to all individuals. Three different regions (distal, medium, and proximal with respect to the venom bulb) of the venom duct were analyzed independently. Diversity (in terms of number of distinct members) of conotoxin precursor superfamilies increased toward the distal region whereas transcripts detected toward the proximal region showed higher expression levels. Only the superfamilies A and I3 showed statistically significant differential expression across regions of the venom duct. Sequences belonging to the alpha (motor cabal) and kappa (lightning-strike cabal) subfamilies of the superfamily A were mainly detected in the proximal region of the venom duct. The mature peptides of the alpha subfamily had the α4/4 cysteine spacing pattern, which has been shown to selectively target muscle nicotinic-acetylcholine receptors, ultimately producing paralysis. This function is performed by mature peptides having a α3/5 cysteine spacing pattern in piscivorous cone species from the Indo-Pacific region, thereby supporting a convergent evolution of piscivory in cones.

Venomics Reveals Venom Complexity of the Piscivorous Cone Snail, Conus tulipa

“…Transcriptomics uncovered 764 conotoxin precursors that were classified into 16 known superfamilies across the two specimens, with two additional superfamilies identified as unique to one specimen. Despite this superfamily overlap, 10% of the identified conotoxin precursors were found in both specimens, representing the venom ‘fingerprint’ for C. tulipa , and establishing that much of the dramatic proteomic variation previously reported [12] arises at the mRNA level [8,19,21,46,47,48]. Overall, the venom of C. tulipa is characterized by the expression of non-paralytic peptides previously hypothesized to contribute to the nirvana cabal of net hunting Conus species [22].…”

“…Cone snail venom composition appears to be affected by geography, diet and season [17], however, significant differences between individuals of the same species [8,18,19,20,21] make comparisons difficult and many earlier studies using pooled venom samples ignored the importance of venom variability [22]. Most well-studied Conus venoms have been isolated from fish hunting species that have evolved to target vertebrates [5,23].…”

Conidae phylogenomics and evolution

“…While there is no documented evidence that Indo‐Pacific Gastridium and Pionoconus species feed on other prey than fish, Atlantic/Eastern Pacific Chelyconus species may also consume other molluscs (Olivera et al, ), which may indicate different evolutionary origins of piscivory in these taxa. Moreover, the comparison of the conotoxin repertoires of Indo‐Pacific versus Atlantic/Eastern Pacific cones also supported independent origins of piscivory (Abalde et al, ). If true, many of the modifications in the radular teeth that are characteristic of Pionoconus and Chelyconus would be convergent.…”

“…Cone predatory capacity relies on a sophisticated venom system, formed by hollow harpoon‐like radular teeth, which inject a cocktail of hundreds of different peptides named conotoxins (Li et al, ; Norton & Olivera, ; Peng et al, ). The great specificity and biological potential of conotoxins have attracted the interest of pharmacological research (Miljanich, ; Yang et al, ), and venom gland transcriptomics are currently the main tool for cataloguing the cocktail composition in the different species (Abalde, Tenorio, Afonso, & Zardoya, ; Barghi, Concepcion, Olivera, & Lluisma, ; Dutertre et al, ; Hu, Bandyopadhyay, Olivera, & Yandell, ; Li et al, ; Peng et al, ). In this regard, understanding the evolutionary processes involved in conotoxin diversification and adaptation to different preys requires a robust phylogeny of cones.…”

Conodipine-P1-3, the First Phospholipases A2 Characterized from Injected Cone Snail Venom*

“…The first conodipine described was a partial sequence for conodipine-M (Cdpi-M), isolated from the dissected venom of C. magus (31). Recently, conodipines were reported from the transcriptome of C. consors (32), C. victorae (33), C. tribblei (34), C. lenavati (UniProt A0A0K8TTR8), C. monile (UniProt A0A161J284), C. ermineus (35) and C. geographus (36). Using sequences from tryptic peptides and the transcriptome, ten conodipines were found in the dissected venom of C. geographus, which differed in sequence and inter-cysteine loop spacing.…”