Abstract
Nucleobase-Ascorbate Transporter (NAT) family includes ascorbic acid, nucleobases, and uric acid transporters: With 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. Using phylogenetic and synteny analysis, we identify a fifth member of the vertebrate slc23 complement (slc23a5), present 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, using available transcriptomic data, 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 the brain. The biological relevance of the retention of an extra transporter in fish and amphibians is discussed.
Highlights
Ascorbic acid is an essential enzyme cofactor, participating in collagen and norepinephrine synthesis, as well as a potent antioxidant and free radical scavenger [1,2]
Through database mining and phylogenetic analysis, we detected the presence of a novel gene, slc23a5, found in neopterygians (Holostei and Teleostei) and amphibians (Figures 1 and S1)
Subsequent loss of slc23a5 in chondrichthyans was further supported by the conservation of the genomic locus in Callorhynchus milii (Australian ghostshark) (Figure S2)
Summary
Ascorbic acid (or its salt form ascorbate) is an essential enzyme cofactor, participating in collagen and norepinephrine synthesis, as well as a potent antioxidant and free radical scavenger [1,2]. Anthropoid primates, teleost fish, Guinea pigs, some bats, and Passeriformes bird species, lack a functional L-gulono-Υ-lactone oxidase (GLO) gene and, the ability to catalyze the last step of ascorbic acid synthesis [3,4]. The scattered loss of the GLO gene was suggested to evolve neutrally, with ascorbic acid requirements being met by dietary intake [3]. Human-biased research has suggested alternative physiological functions for uric acid or urate (uric acid salts), such as antioxidant and free radical scavenger, to ascorbic acid, counterbalancing disease-related oxidative stress [6,7,8].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
