The Venom Repertoire of Conus gloriamaris (Chemnitz, 1777), the Glory of the Sea

Abstract

The marine cone snail Conus gloriamaris is an iconic species. For over two centuries, its shell was one of the most prized and valuable natural history objects in the world. Today, cone snails have attracted attention for their remarkable venom components. Many conotoxins are proving valuable as research tools, drug leads, and drugs. In this article, we present the venom gland transcriptome of C. gloriamaris, revealing this species' conotoxin repertoire. More than 100 conotoxin sequences were identified, representing a valuable resource for future drug discovery efforts.

Keywords: Conus; Conus gloriamaris; cone snail; conotoxin; venom.

Figure 1

The shell of Conus gloriamaris. At one time, this was among the most prized natural history objects in the world.

Figure 2

Distribution of toxin gene families in C. gloriamaris. Conotoxin expression is dominated by only a few conotoxin gene families. Values represent transcripts per million transcripts (TPM) counts obtained for all sequences belonging to the gene family. The number of individual sequences per toxin gene family is provided in parenthesis.

Figure 3

Sequence alignment of C. gloriamaris O2-superfamily precursor sequences. Precursor sequences of O2_Vc6.22, O2_Vc6.18, O2_Vc6.21, O2_Vc6.26, O2_Vc6.24, O2_contryphan_Vc2 [13], PnVIIA [20], and TxVIIA [19] are shown for comparison in grey and marked with *; Cys, yellow; Signal peptides are underlined in purple and predicted mature peptides are underlined in black/grey. This color scheme is used in all subsequent figures.

Figure 4

C. gloriamaris T-superfamily precursor sequences. *, precursor sequences of T_Vc5.7, T_Vc5.20, T_Vc5.23, T_Vc5.16, T_Vc5.8, T_Vc13.1, T_Vc5.19, T_Vc5.22, T_Vc10.1 [13], and MrIA [26] are shown for comparison.

Figure 5

(A) C. gloriamaris O1-superfamily; (B) J-superfamily; (C) H-superfamily precursor sequences. *, precursor sequences of O1_Vc6.36, O1_Vc6.41, O1_Vc6.35, O1_Vc6.30, O1_Vc6.28, O1_Vc6.37, J_Vc14.1, J_Vc14.2, J_Vc14.4, H_Vc7.2, and H_Vc1 [13] are shown for comparison.

Figure 6

(A) C. gloriamaris P-superfamily; (B) U-superfamily; (C) A-superfamily precursor sequences. *, precursor sequences of P_Vc9.2, P_Vc14.5, U_Vc7.3, Vc22.1 [13], Tx1 [30], Vc1.1 [31], and the textile convulsant mature peptide [32], are shown for comparison.

Figure 7

(A) C. gloriamaris M-superfamily; (B) I2-superfamily; (C) B-superfamily precursor sequences. *, precursor sequences of M_Vc3.1, M_Vc3.6, M_Vc3.9, M_conomarphin_Vc1, I2_Vc11.8, I2_Vc11.7, conantokin_Vc1 [13], TxIIIA [34], and the mature peptide of MrIIIA [35] are shown for comparison.

Figure 8

(A) C. gloriamaris B2-superfamil; (B) Con-insulin; (C) prohormone-4; (D) conoCAP precursor sequences. *, precursor sequences of B2_Vc1 [13], Con-Ins Tx1 [39], Con-Ins Vc1, PH4-Vc1 [40], and conoCAP [41] are shown for comparison.

Figure 9

Similarity in cysteine arrangement, chain lengths, and amino acids between the A and B chains of Con-Ins Gm and an endogenous molluscan insulin, and Con-Ins G1 and an endogenous fish insulin. Comparative alignments of Con-Ins Gm and the giant pond snail Lymnaea stagnalis insulin 1 [Uniprot: P07223], and Con-Ins G1 from the venom of C. geographus and the zebrafish Danio rerio insulin [Uniprot: O73727]. Chain lengths and the cysteine number are shown following the sequence. Cysteines are highlighted in yellow. Post-translational modifications are omitted.

Figure 10

(A) C. gloriamaris I1-superfamily; (B) I4-superfamily; (C) cono-NPY; (D) N-superfamily precursor sequences. *, precursor sequences of I1_Vc11.5, I1_Vc11.1, I4_Vc12.1 [13], cono-NPY [45], and Mr15.1 [10] are shown for comparison.

Figure 11

(A) C. gloriamaris E-superfamily; (B) con-ikot-ikot; (C) conorfamide; (D) S-superfamily precursor sequences. *, precursor sequences of E_Vc1, S_Vc8.1 [13], con-ikot-ikot [46], and CNF_Vc1 [47] are shown for comparison.

Figure 12

(A) C. gloriamaris conodipine; (B) O3-superfamily; (C) F-superfamily; (D) conopressin precursor sequences. *, precursor sequences of conodipine, O3_Vc1, F_Vc1 [13], and conopressin-G [11] are shown for comparison.

Figure 13

(A) C. gloriamaris MKAVA-superfamily; (B) MSRLF-superfamily; (C) MMLFM-superfamily; (D) MLSML-superfamily precursor sequences. *, precursor sequences of G114, G118, G120 [52], C. caracteristicus ‘putative conotoxin’ (GenBank: B0L0Y6.1), and Cln_SF6_1 [54] are shown for comparison.

Figure 14

C. gloriamaris and some other species in the subgenus Cylinder. Left, C. gloriamaris; Second column, C. victoriae (Top), C. textile (Bottom); Third column, Conus legatus; Fourth column, Conus retifer (Top), Conus aureus (Bottom).

Figure 15

Conus gloriamaris shares a near-identical toxin gene family repertoire to the closely-related species Conus victoriae. (A) Phylogenetic tree of various Conus species highlighting close relatedness of C. gloriamaris and C. victoriae (subgenus Cylinder). Neighbor-joining tree of concatenated 12S, 16S and COI sequences was generated (Jukes-Cantor model) using Geneious version 8.1.3. Sequences were obtained from GenBank. Conus imperialis was used as an outgroup. Branch labels show consensus support (%); (B) A comparison of the expressed toxin gene family repertoire of C. gloriamaris and C. victoriae. Heat map is indicative of individual conotoxin number in each gene family.