Tracing the Evolutionary Expansion of a Hyperdiverse Antimicrobial Peptide Gene Family in Mytilus spp.: The MyticalinDB Resource

Background: The overwhelming majority of the antimicrobial peptides (AMPs) studied in mussels (Mytilus spp.) so far are specifically expressed by hemocytes and display compact disulfide-stabilized structures. However, gill-specific myticalins play a role in mucosal immunity and are one of the very few examples of known molluscan AMPs lacking cysteine residues. Methods: We investigate the molecular evolution of myticalins, compiling a collection of sequences obtained by carefully annotating 169 genome assemblies of different Mytilus species. We determine the gene presence/absence patterns and gene expression profiles for the five myticalin subfamilies, including the newly reported myticalin E. Results: All sequences are deposited in MyticalinDB, a novel database that includes a total of 100 unique mature myticalin peptides encoded by 215 protein precursors, greatly enriching the compendium of these molecules from previous reports. Among the five subfamilies, myticalin A and C are the most widespread and highly expressed across all Mytilus species. Interestingly, structural prediction reveals a previously unreported strong amphipathic nature for some myticalins, which may be highly relevant for their biological activity. Conclusions: The results reported in this work support the role of myticalins in gill-associated mucosal immunity and highlight the importance of inter-individual molecular diversity in establishing an efficient response to microbial infections. The newly established MyticalinDB provides a valuable resource for investigating the evolution and extraordinary molecular diversity of this AMP family