Functional and Evolutionary Insights of NR1J1 Nuclear Receptors: A Diversified Sensing Weapon in Bivalves

Nuclear receptors (NRs) of the NR1J1 group have been described in aquatic invertebrates and proposed as the evolutionary counterparts of vertebrate NR1I receptors, known for their role in xenobiotic-sensing and detoxification. In bivalves, previous studies have shown that NR1J1 activity and gene expression are modulated by pharmaceuticals, toxins, natural compounds, and algal extracts. However, their functional properties and diversification remain poorly understood. Here, we investigated the function and evolution of NR1J1 receptors in the bivalves Mytilus galloprovincialis and Ruditapes decussatus. We first identified four nr1j1 paralogs in R. decussatus and then integrated phylogenetic analysis, domain identity comparisons, tissue distribution profiling, and luciferase-based transactivation assays to characterize NR1J1 paralogs from both species. The receptors displayed distinct but partially overlapping transactivation profiles in response to confirmed ligands of NR1I and NR1H receptors, natural compounds, plant extracts, and fish bile, indicating paralog- and species-specific differences in ligand responsiveness. Allocholic acid emerged as the most consistent agonist across paralogs, whereas curcumin, carnosic acid, and Ptychopetalum olacoides extract showed more selective response patterns. Tissue profiling revealed broad but non-uniform expression of nr1j1 paralogs across bivalve tissues. Together, these findings underscore that bivalve NR1J1 receptors constitute a functionally diversified chemical-sensing system and provide a framework for future studies addressing ligand-dependent regulation and detoxification pathways.