A novel tumor necrosis factor (TNF) gene present in tandem with theTNF-alpha gene on the same chromosome in teleosts

Abstract

Tumor necrosis factors (TNFs) are pleiotropic cytokines implicated in inflammation, apoptosis, cell proliferation, and a general stimulation of immune system. Although the TNF/lymphotoxin (LT) locus is present in the MHC region of the chromosome in mammals, no such locus has been described from teleosts. Furthermore, in teleosts only the TNF-alpha-like gene has been cloned and analyzed. In this study, for the first time in teleosts, a similar TNF locus has also been found in zebrafish and fugu. This locus harbors a new TNF ligand in tandem with TNF-alpha gene. The fugu and zebrafish TNF locus harbors TNF-alpha and TNF-N genes that are 7.5 kb and 19 kb apart from each other, respectively. Several genes associated with the TNF/LT locus in mammals are found conserved in fish as well. Fish TNF-alpha genes cloned possess a transmembrane domain, two conserved cysteines, and a conserved TNF family signature with a four-exon and three-intron genomic structure. The newly identified TNF-N genes from teleosts are present upstream of TNF-alpha genes in the same transcriptional orientation. However, the coding regions of these genes span into five and four exons in fugu and zebrafish, respectively. The transcription sites in the promoter regions of teleost TNF ligands are fairly conserved in comparison to mammals. Expression analysis indicates a constitutive expression of both the genes in fugu, while differential expression of TNF ligands is seen in zebrafish tissues.