Ancestral Origin and Functional Expression of a Hyaluronic Acid Pathway Complement in Mussels

Hyaluronic acid (HA) is a key extracellular matrix component of vertebrates, where it mediates cell adhesion, immune regulation, and tissue remodeling through its interaction with specific receptors. Although HA has been detected in a few invertebrate species, the lack of fundamental components of the molecular HA pathway poses relevant objections about its functional role in these species. Mining genomic and transcriptomic data, we considered the conservation of the gene locus encoding for the extracellular link protein (XLINK) in marine mussels as well as its expression patterns. Structural and phylogenetic analyses were undertaken to evaluate possible similarities with vertebrate orthologs and to infer the origin of this gene in invertebrates. Biochemical analysis was used to quantify HA in tissues of Mytilus galloprovincialis. As a result, we confirm that the mussel can produce HA (up to 1.02 ng/mg in mantle) and that its genome encodes two XLINK gene loci. These loci are conserved in Mytilidae species and show a complex evolutionary path. Mussel XLINK genes appeared to be expressed during developmental stages in three mussel species, ranking in the top 100 expressed genes in M. trossulus at 17 h post-fertilization. In conclusion, the presence of HA and an active gene with the potential to bind HA suggests that mussels have the potential to synthesize and use HA and are among the few invertebrates encoding this gene.