Abstract
The TLRs and IL-1 receptors have evolved to coordinate the innate immune response following pathogen invasion. Receptors and signalling intermediates of these systems are generally characterised by a high level of evolutionary conservation. The recently described IL-1R1 co-receptor TILRR is a transcriptional variant of the FREM1 gene. Here we investigate whether innate co-receptor differences between teleosts and mammals extend to the expression of the TILRR isoform of FREM1. Bioinformatic and phylogenetic approaches were used to analyse the genome sequences of FREM1 from eukaryotic organisms including 37 tetrapods and five teleost fish. The TILRR consensus peptide sequence was present in the FREM1 gene of the tetrapods, but not in fish orthologs of FREM1, and neither FREM1 nor TILRR were present in invertebrates. The TILRR gene appears to have arisen via incorporation of adjacent non-coding DNA with a contiguous exonic sequence after the teleost divergence. Comparing co-receptors in other systems, points to their origin during the same stages of evolution. Our results show that modern teleost fish do not possess the IL-1RI co-receptor TILRR, but that this is maintained in tetrapods as early as amphibians. Further, they are consistent with data showing that co-receptors are recent additions to these regulatory systems and suggest this may underlie differences in innate immune responses between mammals and fish.
Highlights
The innate immune system is generally well conserved throughout the animal kingdom with the same characteristic features of regulatory components present in species ranging from insects to mammals [1]
In order to determine the evolutionary development of the interleukin 1 receptor type I (IL-1RI) co-receptor Toll-like and Il-1 receptor regulator (TILRR), we identified the TILRR isoform of FREM1 within the genomes of multiple organisms and defined the source of the TILRR peptide sequence within the nucleotide sequence of the FREM1 loci
Alignment of the peptide sequences of human TILRR and FREM1 show that they are identical from R17 of TILRR
Summary
The innate immune system is generally well conserved throughout the animal kingdom with the same characteristic features of regulatory components present in species ranging from insects to mammals [1]. It is increasingly recognized that mechanisms of ligand recognition and co-receptor association, a potent regulator of signal amplification at the level of the receptor complex, are less well conserved [5,6]. In evolutionary terms, such co-receptors appeared relatively late in the development of their respective signaling networks which they control. Recent studies have revealed that fish, which have been shown to possess certain inflammatory receptors, may lack co-receptors found in more modern organisms, suggesting that signaling mechanisms in earlier species are functionally distinct and less refined. Ancient, refinements to the system have continued to arise until more recently and that important differences exist between model organisms used to study inflammation
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