Genetics of sexual development: an evolutionary playground for fish

Abstract

Teleost fishes are the most species-rich clade of vertebrates and feature an overwhelming diversity of sex-determining mechanisms, classically grouped into environmental and genetic systems. Here, we review the recent findings in the field of sex determination in fish. In the past few years, several new master regulators of sex determination and other factors involved in sexual development have been discovered in teleosts. These data point toward a greater genetic plasticity in generating the male and female sex than previously appreciated and implicate novel gene pathways in the initial regulation of the sexual fate. Overall, it seems that sex determination in fish does not resort to a single genetic cascade but is rather regulated along a continuum of environmental and heritable factors.

Figure 1

Reproductive strategies in fish. Fish can be grouped according to their reproductive strategy into unisexuals, hermaphrodites, and gonochorists. Further subdivisions of these three categories are shown with pictures of species exemplifying the strategies. Fish images: Amphiprion clarkii courtesy of Sara Mae Stieb; Hypoplectrus nigricans courtesy of Oscar Puebla; Scarus ferrugineus courtesy of Moritz Muschick; Astatotilapia burtoni courtesy of Anya Theis; Poecilia formosa and Kryptolebias marmoratus courtesy of Manfred Schartl; Trimma sp. courtesy of Rick Winterbottom [serial hermaphroditism has been described in several species of the genus Trimma (Kuwamura and Nakashima 1998; Sakurai et al. 2009; and references therein)].

Figure 2

Sex-determining mechanisms in fish. Sex-determining systems in fish have been broadly classified into environmental and genetic sex determination. For both classes, the currently described subsystems are shown.

Figure 3

Two views on the sex-determining cascade. Classic view on the sex-determining cascade: The prevailing view on sexual development is the one of an initial trigger (environmental or genetic, mostly a presence/absence signal) initiating the sex determination cascade that activates sex differentiation, finally causing the establishment of one gonad type and the corresponding sexual phenotype. In this scenario, the presence of the initial trigger (here exemplified for a male master determiner) activates one cascade, whereas its absence leads to the other sex. Based on this cascade assumption, genes are added stepwise to the exisiting cascade. The cascade thus evolves in a retrograde fashion. The last (i.e., the most downstream) step is the first one to be selected for. This evolution leads to the genetic network of sexual development divided into two steps: sex determination and differentiation (Wilkins 1995, 2005). Sex determination with male and female state as threshold phenotype: Based on a developmental perspective (Crews and Bull 2009; Uller and Helanterä 2011), sexual development is not split into determination and differentiation but rather controlled by a combination of different heritable and external factors influencing cell proliferation and hormone levels with a male and female threshold. Determining regulators evolve via canalization toward major-effect loci influencing the male/female threshold. Note that under this model without a strict hierarchical cascade, major-effect loci could emerge at all levels and are not imposed at the very top of the cascade.

Figure 4

Models for the emergence of new genetic master sex determiners. Three mechanisms mainly influencing the evolution of master SD genes are shown. (1) Based on the classic cascade view, new genes formed by gene duplication or mutation in existing genes can be up-recruited to the top of the cascade (Schartl 2004). (2) Based on the view of SD as a genetic network, gene duplication and/or mutation of a member of the network could create potential material for the evolution of a new master gene without the loss of the ancestral gene. (3) The limited options theory after Marshall Graves and Peichel (2010) proposes that a pool of genes or entire chromosomes are reused in different species to become master determiners. Note that, as shown here, this model does not rely on a hierarchical cascade view of SD.

Figure 5

Possible scenarios for the evolution of fish SD genes. The figure illustrates possible evolutionary paths for the currently known master SD genes in teleost fish: (A) dmrt1bY/dmy, (B) gsdf^Y, (C) amhY, (D) amhr2, and (E) sdY. Horizontal arrows indicate gene duplications; color change of boxes to orange indicates acquisition of master-determining function via mutation (coding or regulatory). Green boxes in E indicate that the genetic network that irf9 belongs to was not related to sex determination before the emergence of sdY.

Figure 6

AMH/AMHR2-signaling pathway. Sertoli cells secrete a precursor form of AMH. After cleavage, an AMH dimer binds to AMHR2, which activates a type I receptor (currently not characterized; mechanism derived from comparisons with other receptors of the TGF-β superfamily). The ligand-receptor complex phosphorylates SMAD proteins, which then form a complex by incorporating Co-SMADs. This complex translocates into the nucleus and regulates gene expression together with transcription factors and cofactors. Figure modified after Fan et al. (2012) and Kikuchi and Hamaguchi (2013) and references therein.