Cartilaginous fish inform the lineage-specific evolution and MHC association of the TLR family

Chondrichthyans (sharks, rays and chimaeras) diverged from other vertebrate lineages over 400 million years ago and possess fully functional innate and adaptive immune systems. They comprise over 1,200 species occupying diverse aquatic habitats, from fresh to marine waters and from shallow to deep seas. Exposure to diverse pathogens through time, together with contemporary ocean warming and habitat degradation driven by climate change, has likely shaped unique immune mechanisms in these species. Toll-like receptors (TLRs) are central components of innate immunity, recognizing conserved pathogen-associated molecular patterns and initiating immune responses, yet their diversity remains poorly characterized in Chondrichthyans. Here, we characterize the TLR gene repertoire in elasmobranchs (sharks and rays) using genomic and transcriptomic data. We identify orthologs spanning all known vertebrate TLR families, including genes shared with agnathans as well as gnathostome-specific genes, and detect lineage-specific patterns of TLR duplication and loss, particularly in squaliform sharks and rays. Molecular evolution analyses indicate that most elasmobranch TLRs are under strong purifying selection, with positively selected sites in all genes, consistent with ongoing adaptation to pathogen-and environment-driven pressures. Several TLRs co-localize with genomic regions enriched in immune genes, including MHC paralogous regions, suggesting an ancestral genomic hotspot for vertebrate immunity.