Comparative genomic evidence for duplication of TLR1 subfamily and miiuy croaker TLR1 perceives LPS stimulation via MyD88 and TIRAP

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Being indispensable pattern recognition receptors in innate immune responses in host protection, Toll-like receptors (TLRs) play an important role in pathogen recognition. Fish TLRs exhibit high variety and distinct features, although little is known about their function on ligand recognition and signaling pathway in fish. This paper reports the evolutionary spectrum of the TLR1 subfamily (referred to as TLR1, TLR6, and TLR10) as determined using the comparative genomic approach. We hypothesized that the TLR1 subfamily underwent two rounds of gene duplication events; the first duplication occurred prior to the divergence of amphibians, and the second one occurred prior to the divergence of eutherians. To further study the function of fish TLR1, we identified miiuy croaker (Miichthys miiuy) TLR1 (mmiTLR1) and determined its potential ability to perceive Vibrio anguillarum and lipopolysaccharide stimulation. Data further suggested that mmiTLR1 is dependent on TIRAP and MyD88 for signal transmission. In addition, immunocytochemistry showed the speculative interaction between MyD88 and mmiTLR1 TIR domain. Overall, we systematically and comprehensively analyzed evolution of TLR1 subfamily and the function of mmiTLR1, which will provide the basis for future scientific research on fish TLRs.HighlightsTLR1 is intron-poor gene and the introns mainly distribute in 5′UTR.Two rounds gene duplications may occur in vertebrate TLR1 subfamily.MmiTLR1 can make response to lipopolysaccharide (LPS) stimulation.MmiTLR1 depends on mmiTIRAP and mmiMyD88 for signal transmission.

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