Molecular evolution of interleukin-1β within vertebrates
The principal aim of this investigation is to sequence IL-1β within a number of non-mammalian vertebrates, in order to establish a better idea of when this molecule arose within vertebrate evolution. IL-1β is a good candidate to study as it has been shown to play many important roles within the immune and neuroendocrine system of mammals. Using an homology cloning approach IL-1β has been sequenced from a cartilaginous fish (Scyliorhinus caniculus), a number of bony fish (Pleuronectes platessa, Dicentrarchus labrax and Carassius auratus), an amphibian (Xenopus laevis) and a primitive mammal (Ornithorhynchus anatinus). All nucleotide sequences are found to contain differing numbers of mRNA instability motifs, characteristic of genes which code for inflammatory mediators. All amino acid sequences contain the IL-1 family signature and show highest conservation in the regions which are predicted to form the 12β-sheets, important for the folding of the active molecules. The O. anatinus IL-1β contains an ICE cut site which is in keeping with all other mammalian sequences, whereas none of the other sequences contain this cut site as found in all non-mammalian vertebrates to date. Like all other IL-1β molecules they contain no signal peptides, indicating that these molecules are not secreted through the classical golgi/endoplasmic reticulum route. Within C. auratus two different IL-1β genes were sequenced, IL-1β and IL-1β2. The second gene contained a different IL-1 family signature to the first and also had regions of coding sequence missing, a region at the 5- end, which is presumed to be due to the loss of an exon and two other regions, one which is 3 bp and the other 12 bp long. The second gene also showed differences in the 3' UTR sequence and position of its stop codon when compared to the first gene.