Stress, novel sex genes and epigenetic reprogramming orchestrate socially-controlled sex change

Abstract

Bluehead wrasses undergo dramatic, socially-cued female to male sex change. We apply transcriptomic and methylome approaches in this wild coral reef fish to identify the primary trigger and subsequent molecular cascade of gonadal metamorphosis.Our data suggest that the environmental stimulus is exerted via the stress axis, that repression of the aromatase gene (encoding the enzyme converting androgens to estrogens) triggers a cascaded collapse of feminizing gene expression, and identifies notable sex-specific gene 2 neofunctionalization. Furthermore, sex change involves distinct epigenetic reprogramming and an intermediate state with altered epigenetic machinery expression akin to the early developmental cells of mammals. These findings reveal at a molecular level how a normally committed developmental process remains plastic and is reversed to completely alter organ structures.

The neurogenetics of sexually dimorphic behaviors from a postdevelopmental perspective

“…Prime examples are found in teleost fishes, many of which naturally switch sex at some point in their adult life, often in response to changes in their social environment. 32,88,89 Unlike the gonad-driven sex determination in mammals we describe above, brain development in these sequential vertebrate hermaphrodites precedes gonad development and differentiation. In fact, recent studies suggest that the regulation of both gonad and brain sex are, to some extent, decoupled in these fishes via the action of independent sex-determination epigenetic programs and gene networks in each tissue.…”

“…This program, in turn, supports sex-specific cellular functions via sex-biased transcriptional and physiological states. [27][28][29][30][31][32][33][34] Because of their genetic tractability, the neuronal sexdetermination pathways of the fruit fly Drosophila melanogaster and the lab mouse Mus musculus are particularly well described. Both species produce sexually dimorphic male and female forms, which exhibit multiple sex-dependent morphological, neuroanatomical and behavioral traits.…”

“…Sex-specific remodeling of the gonadal tissues subsequently follows. 32,88,92,93 Another example of a plastic sex determination system is exhibited by species with simultaneous hermaphrodites, in which male and female tissues coexist within a single individual. Such systems are common in diverse invertebrate phyla including the platyhelminthes, annelids and molluscs.…”

Peer Review #2 of "Conservation and diversity in expression of candidate genes regulating socially-induced female-male sex change in wrasses (v0.1)"

“…A paralogue of dmrt1 (dmy) has also become the male sex-determining gene in several fish species [17][18][19]. However, in protogynous hermaphrodites studied to date, changes in dmrt1 expression regularly appear downstream of other genes, suggesting that dmrt1 may be more important in progressing rather than initiating sex change [20,21]. Anti-Müllerian hormone, Amh, a multifunctional member of the transforming growth factor-ß (TGF-ß) family, also plays a key role in regulating germ cell development in vertebrates, especially in males [22][23][24].…”

“…Amh is the male-determining factor in Patagonian pejerrey (Odontesthes hatcheri) [25] and Nile tilapia (Oreochromis niloticus) [26], while the Amh receptor, Amhr2, determines maleness in several species of Takifugu pufferfish [27]. A transcriptome-wide expression analysis of bluehead wrasse found amh and amhr2 to be the earliest male-pathway genes upregulated during female to male sex change, concurrent with arrested expression of cyp19a1a and prior to the appearance of male tissues [21]. Expression of amh also increased during early protogynous sex change in ricefield eel (Monopterus albus) [28], and decreased during protandrous sex change in Red Sea clownfish (Amphiprion bicinctus) [29].…”