title: Determination of onset of sexual maturation and mating behavior by melanocortin receptor 4 polymorphisms.
abstract: Polymorphisms in reproductive strategies are among the most extreme and complex in nature. A prominent example is male body size and the correlated reproductive strategies in some species of platyfish and swordtails of the genus Xiphophorus. This polymorphism is controlled by a single Mendelian locus (P) that determines the onset of sexual maturity of males. Because males cease growth after reaching puberty, this results in a marked size polymorphism. The different male size classes show pronounced behavioral differences (e.g., courtship versus sneak mating), and females prefer large over small males. We show that sequence polymorphisms of the melanocortin receptor 4 gene (mc4r) comprise both functional and non-signal-transducing versions and that variation in copy number of mc4r genes on the Y chromosome underlies the P locus polymorphism. Nonfunctional Y-linked mc4r copies in larger males act as dominant-negative mutations and delay the onset of puberty. Copy number variation, as a regulating mechanism, endows this system with extreme genetic flexibility that generates extreme variation in phenotype. Because Mc4r is critically involved in regulation of body weight and appetite, a novel link between the physiological system controlling energy balance and the regulation of reproduction becomes apparent.
authors.affiliation: Physiological Chemistry I, Biocenter, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany.
authors.forename: Kathrin P
authors.initials: KP
authors.lastname: Lampert
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schmidt
authors.forename: Petra
authors.initials: P
authors.lastname: Fischer
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Volff
authors.forename: Carsten
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Jenny
authors.initials: J
authors.lastname: Muck
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lohse
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ryan
authors.forename: Manfred
authors.initials: M
authors.lastname: Schartl
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D049628:Body Size / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D003532:Cyprinodontiformes / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics* / Q000378:metabolism; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000502:physiology*; D012741:Sexual Maturation / Q000235:genetics*
chemical_list: D044105:Receptor, Melanocortin, Type 4; D000242:Cyclic AMP