title: Molecular evolution of kiss2 genes and peptides in vertebrates.
abstract: The kiss1 peptide (kisspeptin), a product of the kiss1 gene, is one of the key neuropeptides regulating vertebrate reproduction. In 2009, we identified a paralogous gene of kiss1 in the brain of amphibians and named it kiss2. Currently, the presence of the kiss2 gene and the kiss2 peptide is still obscure in amniotes compared with that in other vertebrates. Therefore, we performed genome database analyses in primates and reptiles to investigate the molecular evolution of the kiss2 gene in vertebrates. Because the mature kiss2 peptide has been identified only in amphibians, we further performed immunoaffinity purification and mass spectrometry to identify the mature endogenous kiss2 peptide in the brains of salmon and turtle that possessed the kiss2 gene. Here we provide the first evidence for the presence of a kiss2-like gene in the genome database of primates including humans. Synthetic amidated human KISS2 peptide activated human GPR54 expressed in COS7 cells, but nonamidated KISS2 peptide was inactive. The endogenous amidated kiss2 peptide may not be produced in primates because of the lack of an amidation signal in the precursor polypeptide. The kiss2-like gene may be nonfunctional in crocodilians because of premature stop codons. We identified the mature amidated kiss2 peptide in turtles and fish and analyzed the localization of kiss2 peptide mRNA expression in fish. The present study suggests that the kiss2 gene may have mutated in primates and crocodilians and been lost in birds during the course of evolution. In contrast, the kiss2 gene and mature kiss2 peptide are present in turtles and fish.
authors: PhD, Professor, Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, Center for Medical Life Science of Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. k-tsutsui@waseda.jp.
authors: Tomohiro
authors: T
authors: Osugi
authors: Naohito
authors: N
authors: Ohtaki
authors: Yuya
authors: Y
authors: Sunakawa
authors: You Lee
authors: YL
authors: Son
authors: Makoto
authors: M
authors: Ohkubo
authors: Masayuki
authors: M
authors: Iigo
authors: Masafumi
authors: M
authors: Amano
authors: Kazuyoshi
authors: K
authors: Tsutsui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017683:Oncorhynchus / Q000235:genetics / Q000378:metabolism*; D011323:Primates; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D026801:Synteny; D014426:Turtles
chemical_list: D018076:DNA, Complementary; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1