A taxonomically-restricted Uric Acid transporter provides insight into antioxidant equilibrium

Nucleobase-Ascorbate Transporter (NAT) family includes ascorbic acid, nucleobases and uric acid transporters, with a broad evolutionary distribution. In vertebrates, four members have been previously recognized, the ascorbate transporters Slc23a1 and Slc3a2, the nucleobase transporter Slc23a4 and an orphan transporter SLC23A3. Here we identify a fifth member of the vertebrate slc23 complement ( slc23a5 ), expressed in neopterygians (gars and teleosts) and amphibians, and clarify the evolutionary relationships between the novel gene and known slc23 genes. Further comparative analysis puts forward uric acid as the preferred substrate for Slc23a5. Gene expression quantification suggests kidney and testis as major expression sites in Xenopus tropicalis (western clawed frog) and Danio rerio (zebrafish). Additional expression in brain was detected in D. rerio , while in the Neoteleostei Oryzias latipes (medaka) slc23a5 expression is restricted to brain. The biological relevance of the retention of an extra transporter in fish and amphibians is examined: with respect to the (1) antioxidant role of uric and ascorbic acid in seminal fluid and brain, (2) the ability to endogenously synthesize ascorbic acid and (3) the morphological adaptations of the male urogenital system.