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

Abstract

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 gnathostome mtnr genes have a conserved gene organization with two exons, except for mtnr1b paralogs of some teleosts that show intron gains. Phylogeny and synteny analyses demonstrate the presence of four mtnr subtypes, MTNR1A, MTNR1B, MTNR1C, MTNR1D that arose from duplication of an ancestral mtnr during the vertebrate tetraploidizations (1R and 2R). In tetrapods, mtnr1d was lost, independently, in mammals, in archosaurs and in caecilian amphibians. All four mtnr subtypes were found in two non-teleost actinopterygian species, the spotted gar and the reedfish. As a result of teleost tetraploidization (3R), up to seven functional mtnr genes could be identified in teleosts. Conservation of the mtnr 3R-duplicated paralogs differs among the teleost lineages. Synteny analysis showed that the mtnr1d was 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 of mtnr1a, mtnr1b, and mtnr1c. Loss of one of the 3R-paralogs depends on the lineage: mtnr1ca was lost in euteleosts whereas mtnr1cb was lost in osteoglossomorphs and several ostariophysians including the zebrafish. We investigated the tissue distribution of mtnr expression 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 affects mtnr expression levels in a gene-specific and tissue-specific manner. This study provides new insights into the repertoire diversification and functional evolution of the mtnr gene family in vertebrates.

Effects of Melatonin on Anterior Pituitary Plasticity: A Comparison Between Mammals and Teleosts

“…Multiple Mtnr paralogues are expressed in the pituitary of teleosts ( 28 ). For instance, qPCR analysis detected the mRNA of four Mtnr paralogues in the pituitary of medaka ( 27 ).…”

“…Melatonin acts through several different receptors (MTNR), belonging to the G‐protein coupled receptor superfamily ( 24 ). Four sub‐groups of Mtnr, arising from the 1R and 2R, have been characterized in vertebrates: MTNR1A (Mel1a or MT1), MTNR1B (Mel1b or MT2), MTNR1C (Mel1c or GPR50), and MTNR1D (Mtnr1A-like or Mel1d) ( 25 – 28 ). In mammals, melatonin action is mediated only through two MTNR paralogues, MTNR1A and MTNR1B, since the Mtnr1d gene was lost in the mammalian lineage and MTNR1C lost its ability to bind melatonin ( 28 ).…”

“…Four sub‐groups of Mtnr, arising from the 1R and 2R, have been characterized in vertebrates: MTNR1A (Mel1a or MT1), MTNR1B (Mel1b or MT2), MTNR1C (Mel1c or GPR50), and MTNR1D (Mtnr1A-like or Mel1d) ( 25 – 28 ). In mammals, melatonin action is mediated only through two MTNR paralogues, MTNR1A and MTNR1B, since the Mtnr1d gene was lost in the mammalian lineage and MTNR1C lost its ability to bind melatonin ( 28 ). Teleosts may possess up to 7 Mtnr paralogues (excluding the polyploid cyprinids), arising from the 3R and 4R ( 25 , 28 ).…”

“…In mammals, melatonin action is mediated only through two MTNR paralogues, MTNR1A and MTNR1B, since the Mtnr1d gene was lost in the mammalian lineage and MTNR1C lost its ability to bind melatonin ( 28 ). Teleosts may possess up to 7 Mtnr paralogues (excluding the polyploid cyprinids), arising from the 3R and 4R ( 25 , 28 ). MTNR affects different intracellular signaling pathways, including cAMP/PKA, via G i proteins (MTNR1A and MTNR1B) ( 29 , 30 ), PLC/PKC via G q ‐proteins (MTNR1A and MTNR1C) ( 31 ) and cGMP via G i/o proteins (MTNR1B) ( 32 , 33 ).…”

“…Interestingly, melatonin receptors in Atlantic salmon ( Salmo salar ) increase cAMP when activated by melatonin ( 25 ). The broad distribution of MTNR expression in the central nervous system (including the pituitary) and peripheral tissues suggests melatonin can have widespread effects ( 28 , 34 ).…”