Gene Amplification and Functional Diversification of Melanocortin 4 Receptor at an Extremely Polymorphic Locus Controlling Sexual Maturation in the Platyfish

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Jean-Nicolas Volff - (Autor:in)
  • Yvonne Selz - (Autor:in)
  • Carsten Hoffmann - (Autor:in)
  • Alexander Froschauer - , Umweltmonitoring und Endokrinologie (FoG), Professur für Zoologie und Entwicklungsbiologie (Autor:in)
  • Christina Schultheis - (Autor:in)
  • Cornelia Schmidt - (Autor:in)
  • Qingchun Zhou - (Autor:in)
  • Wolfgang Bernhardt - (Autor:in)
  • Reinhold Hanel - (Autor:in)
  • Astrid Boehne - (Autor:in)
  • Frederic Brunet - (Autor:in)
  • Beatrice Segurens - (Autor:in)
  • Arnaud Couloux - (Autor:in)
  • Sylvie Bernard-Samain - (Autor:in)
  • Valerie Barbe - (Autor:in)
  • Catherine Ozouf-Costaz - (Autor:in)
  • Delphine Galiana - (Autor:in)
  • Martin J. Lohse - , Julius-Maximilians-Universität Würzburg (Autor:in)
  • Manfred Schartl - (Autor:in)

Abstract

In two swordtail species of the genus Xiphophorus, the onset of puberty has been shown to be modulated at the P locus by sequence polymorphism and gene copy-number variation affecting the type 4 melanocortin hormone receptor Mc4r. The system works through the interaction of two allelic types, one encoding wild type and the other dominant-negative receptors. We have analyzed the structure and evolution of the P locus in the platyfish Xiphophorus maculatus, where as many as nine alleles of P determining the onset of sexual maturity in males and females, fecundity in females, and adult size in males are located on both the X and Y chromosomes in a region linked to the master sex-determining locus. In this species, mc4r has been amplified to up to 10 copies on both the X and Y chromosomes through recent large serial duplications. Subsequently, mc4r paralogues have diverged considerably into many different subtypes. Certain copies have acquired new untranslated regions through genomic rearrangements, and transposable element insertions and other mutations have accumulated in promoter regions, possibly explaining observed deviations from the classical mc4r transcriptional pattern. In the mc4r-coding sequence, in-frame insertions and deletions as well as nonsense and missense mutations have generated a high diversity of Mc4r-predicted proteins. Most of these variants are expressed in embryos, adults, and/or tumors. Functional receptor characterization demonstrated major divergence in pharmacological behavior for Mc4r receptors encoded by different copies of platyfish mc4r, with differences in constitutive activity as well as binding and stimulation by hormones. The high degree of allelic and copy-number variation observed between individuals can explain the high level of polymorphism for sexual maturation, fecundity, and body size in the platyfish: multiple combinations of Mc4r variants with different biochemical properties might interact to modulate the melanocortin signaling that regulates the hypothalamus–pituitary–gonadal axis.

Details

OriginalspracheEnglisch
Seiten (von - bis)1337-1352
Seitenumfang16
FachzeitschriftGenetics
Jahrgang195
Ausgabenummer4
PublikationsstatusVeröffentlicht - 1 Dez. 2013
Peer-Review-StatusJa

Externe IDs

Scopus 84889000551

Schlagworte