Abstracts (first author)
Evolutionary study of RDH10 gene family reveals a novel member retained in ectothermic vertebrates
Nuclear receptor-mediated retinoic acid signalling is crucial for organ modelling and maintenance. Active retinoid biosynthesis involves a two-step oxidation cascade: retinol oxidation followed by retinaldehyde dehydrogenase activity, suggested to coordinate retinoic acid supply. Recent studies have highlighted the functional role of a membrane-associated retinol dehydrogenase (RDH10) in the first oxidation step in mammals. This enzyme displays tissue and time-specific expression patterns that correlate with both retinoic acid and retinaldehyde dehydrogenase activities: suggestive of an additional checkpoint for retinoic acid regulation. Here we investigated the evolution of chordate rdh10. While a single copy, rdh10a, is observed in birds and mammals, reptiles, amphibians and teleosts exhibit an additional uncharacterized gene, rdh10b. Both rdh10a and rdh10b have duplicate copies in teleosts. Phylogenetic and paralogy analysis revealed that vertebrate rdh10a and rdh10b resulted from whole genome duplication in stem vertebrate evolution; interestingly, with significant functional divergence amongst paralogues. Following duplication, rdh10b was lost in warm-blooded lineages and retained in cold-blooded animals. Both enzymes exhibit conserved reaction cores and tri-dimensional folding; yet, the membrane-association designs appear different: unlike RDH10A, topology predictions advocate for RDH10B solubility. Also, a unique negatively charged insertion is observed in RDH10A isoforms. Gene expression patterns in teleosts, D. rerio and O. nicotilus, were also examined. While rdh10a is ubiquitously expressed, rdh10b expression is typically restricted to gonads, skin, and brain, and is concomitant with the onset of pigmentation and circulation during teleost embryonic development. Together these results support a functional specialization within the rdh10 family and emphasize a dichotomy among vertebrates according to thermal homeostasis mechanisms.