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.

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

“…Defective copies have lost their capability for signal transduction because microdeletions have removed important cysteine residues from the carboxy-terminal region of the receptor. Such defective copies were detected only in males, being located on the Y chromosome (Lampert et al 2010). Copy-number variation correlating with mc4r expression levels was observed for the defective mc4r copies in males: the highest copy-number and expression levels were found in large late-maturing males, while small early maturing males showed low copy number and low levels of expression.…”

“…In contrast, X. nigrensis and X. multilineatus, two swordtail species distantly related to X. maculatus within the genus Xiphophorus (Kang et al 2013), present only three major P-determined male phenotypes (small/ early maturing, large/late-maturing, and one intermediate phenotype). In these species, it has been shown that puberty onset, body size, and reproductive behavior are modulated by sequence polymorphism and gene copy-number variation affecting the type 4 receptor for melanocortin hormones, Mc4r (Lampert et al 2010).…”

“…Through genetic analysis it was shown that mc4r copies are located on the sex chromosomes of X. nigrensis and X. multilineatus (Lampert et al 2010). However, no genomic data are available to assess the origin, structure, and evolution of the P locus in any Xiphophorus species.…”

Melanocortin-4 Receptor in Fish: A Review

“…Moreover, the MC4R was found to be highly expressed in gonads of several fi sh, such as goldfi sh [42], Ya-fi sh [30], and snakeskin gourami [45]. In addition, some previous studies revealed that MC4R copies located on the sex chromosomes participate in the functional modulation of onset of sexual maturity in both male and female swordtails and platyfi sh, suggesting the potential participation of MC4R in the regulation of reproduction [31,46]. Hence, understanding how MC4R mediates the reproductive function in economically important species is important for artifi cial breeding.…”

Tactic-dependent plasticity in ejaculate traits in the swordtail Xiphophorus nigrensis

“…Male body size depends on a Y-linked polymorphism that induces sexual maturation and dramatically slows growth [11]. Males that mature at a small size obtain fertilizations by coercively sneaking copulations while males of large and intermediate size court females but rarely sneak [12].…”