A zebrafish gene with sequence similarities to human uromodulin and GP2 displays extensive evolutionary diversification among teleost and confers resistance to bacterial infection

In the process of investigating synaptic changes happening to mutants lacking postsynaptic receptors in the neuromuscular junction, we focused on a hitherto uncharacterized zebrafish gene <i>zgc153932</i> whose expression was increased in the RNAseq and droplet digital PCR (ddPCR) analysis of a paralyzed mutant <i>sofa potato</i>. The <i>zgc153932</i> gene which we named <i>omcin5 (omc5)</i> showed amino acid sequence similarity to human <i>uromodulin</i> and <i>GP2</i>, which are expressed in epithelial cells of the kidney and the gut respectively and bind to bacteria pili. <i>omc5</i> had 14 paralogues in a ∼400 KB region on the chromosome 12 of the zebrafish genome. These genes, named <i>omcin1</i> through <i>15</i>, constitute a gene cluster which presumably arose from recent gene duplications in the zebrafish lineage. An antibody raised against the epitope common to 6-9 genes in the <i>omcin</i> family revealed expression in the cloaca of 1 day post fertilization (dpf) embryos which broadened to the urinary and digestive tracts by 5 dpf. Expression of <i>omc5</i> was increased by exposure of embryos to <i>Escherichia coli (E. coli)</i>. Survival of <i>omc5</i> mutant embryos was shortened in the presence of <i>E. coli</i>, or when they were not maintained in germ-free conditions. Adults <i>omc5</i> mutants also exhibited susceptibility to infection. Other teleost species which had <i>omcin</i>-like genes in their genomes showed a range of gene duplication, resulting in clusters of 1 to >15 <i>omcin</i>-like genes. We hereby identified a new gene family specific to teleost that include a microbial induced gene which confers resistance to bacterial infection.