New Insights Into the Evolutionary History of Melatonin Receptors in Vertebrates, With Particular Focus on Teleosts

In order to improve our understanding of melatonin signaling, we have reviewed and revised the evolutionary history of melatonin receptor genes (mtnr) in vertebrates. All gnathostomemtnr geneshave a conserved gene organization with two exons, except formtnr1bparalogs of some teleosts that show intron gains. Phylogeny and synteny analyses demonstrate the presence of fourmtnrsubtypes, MTNR1A, MTNR1B, MTNR1C, MTNR1D that arose from duplication of an ancestralmtnrduring the vertebrate tetraploidizations (1R and 2R). In tetrapods,mtnr1dwas lost, independently, in mammals, in archosaurs and in caecilian amphibians. All fourmtnrsubtypes were found in two non-teleost actinopterygian species, the spotted gar and the reedfish. As a result of teleost tetraploidization (3R), up to seven functionalmtnrgenes could be identified in teleosts. Conservation of themtnr3R-duplicated paralogs differs among the teleost lineages. Synteny analysis showed that themtnr1dwas conserved as a singleton in all teleosts resulting from an early loss after tetraploidization of one of the teleost 3R and salmonid 4R paralogs. Several teleosts including the eels and the piranha have conserved both 3R-paralogs ofmtnr1a, mtnr1b, andmtnr1c. Loss of one of the 3R-paralogs depends on the lineage:mtnr1cawas lost in euteleosts whereasmtnr1cbwas lost in osteoglossomorphs and several ostariophysians including the zebrafish. We investigated the tissue distribution ofmtnrexpression in a large range of tissues in medaka. The medaka has conserved the four vertebrate paralogs, and these are expressed in brain and retina, and, differentially, in peripheral tissues. Photoperiod affectsmtnrexpression levels in a gene-specific and tissue-specific manner. This study provides new insights into the repertoire diversification and functional evolution of themtnrgene family in vertebrates.