Comparative analysis of venom genes in the chromosome-level genomes of two closely related cone snails

Venom cocktails of cone snails are characterized by their dynamic composition and the rapid evolution of toxin-encoding genes due to various selective pressures. The integration of comparative genomics, transcriptomics, and proteomics has emerged as a crucial approach for the comprehensive characterization of venom repertoires and the understanding of venom gene evolution. The venom gland transcriptomes of three individuals of the Canary Island cone snail Kalloconus canariensis had 586 different transcripts, and showed remarkably high intraspecific variability. These transcripts were used to annotate and locate venom genes in the assembled pseudochromosomes of the K. canariensis genome, and comparative genomic analyses were performed with the venom genes of the closely related Mediterranean cone snail Lautoconus ventricosus. A total of 86 orthogroups with counterparts in both genomes were identified, comprising 118 and 159 venom genes from K. canariensis and L. ventricosus, respectively. Synteny analyses comparing the two genomes revealed that most (86%) venom genes were located in relatively conserved genomic regions within homologous pseudochromosomes. Notwithstanding, up to 16 genes were rearranged together with their flanking regions into non-homologous pseudochromosomes, suggesting local genomic reorganizations and/ or transpositions, likely mediated by transposable elements. Comparative analyses of K. canariensis and L. ventricosus genomes revealed a core set of venom genes common to both species, showing overall synteny conservation. In addition, numerous instances of lineage-specific venom locus configurations were detected, suggesting that local tandem gene duplications and losses are major drivers of diversification for this gene family.