Perez-Moreno, J. L.; Katz, P. S.

The phylum Mollusca constitutes one of the most taxonomically and morphologically diverse animal clades; however, the genomic exploration of this group has been hampered by fragmented and taxonomically incomplete transcriptomic resources. To address this fundamental limitation, we present MolluscaGenes, a centralized database that unifies transcriptomes from 299 molluscan species spanning all eight recognized classes, encompassing a broad array of tissues and developmental stages. MolluscaGenes provides searchable databases via BLAST and DIAMOND alongside a suite of 196 molluscan-optimized Hidden Markov Models (HMMs) for sensitive protein family identification. To demonstrate the utility of this resource, we performed a comprehensive phylum-wide characterization of the nicotinic acetylcholine receptor (nAChR) superfamily, recovering 3,586 sequences from over 190 species and resolving 15 distinct phylogenetic clades. This analysis revealed substantial lineage-specific expansions across multiple molluscan classes, the identification of novel clades with substitutions in canonical ligand-binding residues, and the evolutionary placement of chemotactile receptors (CRs) and CR-like sequences as predominantly cephalopod clades within the broader nAChR phylogeny. MolluscaGenes constitutes a foundational resource that will accelerate the elucidation of the unique biology and evolutionary history of Mollusca.