Comparative analysis of the DRADA A-to-I RNA editing gene from mammals, pufferfish and zebrafish

The DRADA gene in mammals encodes an A-to-I RNA editase, an adenosine deami nase that acts on pre-mRNAs to produce site specific inosines. DRADA has be en shown to deaminate specific adenosine residues in a subset of glutamate and serotonin receptors, and this editing results in proteins of altered se quences and functional properties. DRADA thus plays a role in creating prot ein diversity. To study the evolutionary significance of this gene, we have characterized the genomic structure of DRADA from Fugu rubripes, and compa red the protein sequences of DRADA from mammals, pufferfish and zebrafish. The DRADA gene from Fugu is three-fold compacted with respect to the human gene, and contains a novel intron within the large second coding exon. DRAD A cDNAs were isolated from zebrafish and a second pufferfish, Tetraodon flu viatilis. Comparisons among fish, and between fish and mammals, of the prot ein sequences show that the catalytic domains are highly conserved for each gene, while the RNA binding domains vary within a single protein in their levels of conservation. Conservation within the Z DNA binding domain has al so been assessed. Different levels of conservation among domains of differe nt functional roles may reflect differences in editase substrate specificit y and/or substrate sequence conservation. (C) 2000 Elsevier Science B.V. Al l rights reserved.