volume 14 Number 20 1986 Nucleic Acids Research Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene Burton D.Clark 1 , Kathleen L.Collins 2 , Melinda S.Gandy 1 , Andrew C.Webb 2 and Philip E.Auron 13 'Harvard-M.I.T. Division of Health Sciences and Technology, Cambridge, MA 02139, 2 Department of Biological Sciences, Wellesley College, Wellesley, MA 02181 and 'Department of Medicine, The New England Medical Center-Tufts University School of Medicine, Boston, MA 02111, USA Received 10 July 1986; Revised and Accepted 16 September 1986 ABSTRACT We have isolated the human prointerleukin 1 (proIL-1) beta gene from leukocyte and fetal liver libraries. The nucleotide sequence and its gene organization reveals that the proIL-1/9 gene is composed of seven exons with a primary transcription product length of 7,008 nucleotides. The exon sequence agrees well with that of the human proIL-1/J cDNA. Features of interest within the transcriptional unit include conventionally positioned TATA, CAT, and poly-adenylation signals for gene regulation, as well as the signatures of gene duplication via retrotransposition in the form of flanking direct repeats and a genomic poly A tail. The genomic organization of the proIL-1/J gene with respect to the number and position of exon boundaries is strikingly similar to that of the recently reported human proIL-lo gene. Therefore, we hypothesize that the proIL-1^ may have arisen by a reverse transcriptase mediated duplication of the related alpha gene. INTRODUCTION The isolation of large quantities of pure interleukin 1 (IL-1) proteins required for the identification of biological properties and activities has been a problem for many years. One direction taken to solving this has been the cloning and sequencing of IL-1 cDNA from three different species. Analysis of these cDNA clones have identified two distinct forms of IL-1 precursor denoted proIL-la and proIL-10 [1, 2, 3, 4]. Characterization and expression of the proIL-la and proIL-10 cDNA has allowed extensive studies on the biological properties of IL-1 [5, 6). However, little is known about the molecular regulation of EL-1 expression. As a first step in understanding the regulation, we report here the cloning, sequencing, and characteriiation of the entire human proIL-1/7 gene and compare it to the recently published human proIL-la gene sequence [7]. The existence of two distantly related proIL-1 genes coding for two functionally similar proteins raises evolutionary issues of origin and diversification. Of particular interest, the proIL-10 gene may be derived from the proIL-la gene via an RNA-mediated duplication-transposition event. Within eukaryotic genomes, there are many examples of processed genes possibly formed by the reverse transcription of cellular RNA. These © IR L Press Limited, Oxford, England. 7897 by guest on June 22, 2016 http://nar.oxfordjournals.org/ Downloaded from