Evolution and expression of TLR5a and TLR5b in lamprey (Lampetra japonica)

The lamprey serves as a key model organism for studying the origin and evolution of species, embryonic development, and the immune system. The immune system primarily relies on pattern recognition receptors, including Toll-like receptors (TLRs), with Toll-like receptor 5 (TLR5) having a particularly complex evolutionary history. Currently, although TLR5 is being identified in an expanding array of taxonomic groups, a comprehensive study on its evolutionary aspects is yet to be conducted. In this study, we identified Lj-TLR5a and Lj-TLR5b in Lampetra japonica and examined their distribution across various tissues in this species. Furthermore, we conducted preliminary investigations into their immune functions and discovered that, as primitive genes, they are highly sensitive to various pathogens. Upon recognizing flagellar proteins, both Lj-TLR5a and Lj-TLR5b work together; however, these TLRs may function independently in response to other stimuli. Subsequently, we performed comprehensive structural and evolutionary analyses of the TLR5 family, incorporating TLR5 data from various species at different evolutionary stages. Our findings revealed that TLR5a and TLR5b in lamprey are in a relatively primitive evolutionary state. Meanwhile, TLR5L differentiated during the early stages of evolution and exhibits a pseudogenic trend throughout this evolutionary process; notably, this TLR is currently preserved only in certain amphibian and reptile species. In cartilaginous fish, only one type of TLR5 is usually retained, whereas bony fish typically possess both TLR5 and TLR5S. TLR5S has a relatively simple structure, likely arising from repetitive whole-genome events in bony fishes. Among bony fishes, flesh-finned fish were found to retain only one TLR5, which eventually evolved into the TLR5 found in quadrupeds. In summary, this study provides significant insights into the origin and evolution of the TLR5 family by analyzing the evolutionary status and immune functions of Lj-TLR5a and Lj-TLR5b in Japanese lampreys.