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Additionally, <jats:italic>MTNR1a-like<\/jats:italic> genes have been identified in teleostean species as a fish-specific subtype of MTNR1a. However, similar molecules to this <jats:italic>MTNR1a-like<\/jats:italic> gene can be found in some reptiles upon searching the DNA database. We hypothesized that a vertebrate can essentially have four functional subtypes of MTNR as ohnologs. Thus, in the present study we examined the molecular phylogeny, expression patterns and pharmacological profile(s) using the teleost medaka (<jats:italic>Oryzias latipes<\/jats:italic>). The four conserved subtypes of MTNR (MTNR1a, MTNR1b, MTNR1c and MTNR1a-like) in vertebrates were classified based on synteny and phylogenetic analysis. The fourth MTNR, termed MTNR1a-like, could be classified as MTNR1d. It was observed by using RT-qPCR that expression patterns differed amongst these subtypes. Moreover, <jats:italic>mtnr1a<\/jats:italic>, <jats:italic>mtnr1c<\/jats:italic> and <jats:italic>mtnr1a-like<\/jats:italic>\/<jats:italic>mtnr1d<\/jats:italic> expression was elevated during short days compared to long days in diencephalons. All the subtypes were activated by melatonin and transduced signals into the Gi pathway, to perform a cAMP-responsive reporter gene assay. It was shown that MTNR originally consisted of four subtypes: MTNR1a, MTNR1b, MTNR1c and MTNR1d. These subtypes were functional, at least in fish, although some organisms, including mammals, have lost one or two subtypes.<\/jats:p>","DOI":"10.1038\/s41598-019-45925-2","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T10:03:09Z","timestamp":1561975389000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Vertebrates originally possess four functional subtypes of G protein-coupled melatonin receptor"],"prefix":"10.1038","volume":"9","author":[{"given":"Kotowa","family":"Sakai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Ikeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"45925_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0301-0082(98)00078-1","volume":"58","author":"J Falc\u00f3n","year":"1999","unstructured":"Falc\u00f3n, J. 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