Molecular evolution of interleukin-1β within vertebrates

• Main Author: Bird, Steve
• Published: University of Aberdeen 2001
• Subjects: 572.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395251

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 (<I>Scyliorhinus caniculus</I>), a number of bony fish (<I>Pleuronectes platessa</I>, <I>Dicentrarchus labrax </I>and <I>Carassius auratus</I>), an amphibian (<I>Xenopus laevis</I>) and a primitive mammal (<I>Ornithorhynchus anatinus</I>). 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 <I>O. anatinus</I> 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 <I>C. auratus</I> 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.