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. 2012 Sep 25;1(3):484-94.
doi: 10.3390/biology1030484.

Bioinformatics Analysis of the FREM1 Gene-Evolutionary Development of the IL-1R1 Co-Receptor, TILRR

Richard C Hudson  1 , Caroline Gray  2 , Endre Kiss-Toth  3 , Timothy J A Chico  4 , Eva E Qwarnstrom  5
Affiliations

Bioinformatics Analysis of the FREM1 Gene-Evolutionary Development of the IL-1R1 Co-Receptor, TILRR

Richard C Hudson et al. Biology (Basel). .

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.

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Figures

Figure 1
Figure 1
(A) Schematic diagram of Human and Mouse FREM1 pre-mRNA. (B) DNA sequence and peptide translation of human and mouse FREM1 in region of boundary between exons 24 and 25 (upper panel) and TILRR showing genomic sequence and translated peptide.
Figure 2
Figure 2
Comparison of TILRR N-terminal sequence.
Figure 3
Figure 3
Identification of single base mutations responsible for non-homologous sequence in C. familiaris, D. ordii, T. syrichta and E. telfairi.
Figure 4
Figure 4
FREM1 orthologs in fish lack the TILRR N-terminus.
Figure 5
Figure 5
Comparative alignment of coding sequence of FREM1 and TILRR in mammals, amphibians and teleosts.
Figure 6
Figure 6
Evolutionary development of FREM1 and presence of putative TILRR sequence.
See this image and copyright information in PMC

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