Involvement of Androgen Receptor in Sex Determination in an Amphibian Species

Abstract

In mice and humans, the androgen receptor (AR) gene, located on the X chromosome, is not known to be involved in sex determination. In the Japanese frog Rana rugosa the AR is located on the sex chromosomes (X, Y, Z and W). Phylogenetic analysis shows that the AR on the X chromosome (X-AR) of the Korean R. rugosa is basal and segregates into two clusters: one containing W-AR of Japanese R. rugosa, the other containing Y-AR. AR expression is twice as high in ZZ (male) compared to ZW (female) embryos in which the W-AR is barely expressed. Higher AR-expression may be associated with male sex determination in this species. To examine whether the Z-AR is involved in sex determination in R. rugosa, we produced transgenic (Tg) frogs carrying an exogenous Z-AR. Analysis of ZW Tg frogs revealed development of masculinized gonads or ‘ovotestes’. Expression of CYP17 and Dmrt1, genes known to be activated during normal male gonadal development, were up-regulated in the ZW ovotestis. Testosterone, supplied to the rearing water, completed the female-to-male sex-reversal in the AR-Tg ZW frogs. Here we report that Z-AR is involved in male sex-determination in an amphibian species.

Sequential Turnovers of Sex Chromosomes in African Clawed Frogs (Xenopus) Suggest Some Genomic Regions Are Good at Sex Determination

“…In both species, SOX3 and AR are located on the sex chromosomes (Fujii et al 2014; Uno et al 2015). Interestingly, this inference extends even farther: orthologs of AR , SOX3 , and FMR1 are also present on the X chromosome of therian mammals, including humans (Uno et al 2013), and SOX3 is a new trigger for sex determination in a fish ( O. dancena ; Takehana et al 2014).…”

Mammalian X homolog acts as sex chromosome in lacertid lizards

“…Known sex-determining genes in vertebrates are usually homologs of genes involved in gonad differentiation (see, for example, Kikuchi and Hamaguchi, 2013;Bachtrog et al, 2014), and thus a better knowledge of the function of many genes in the ancestral mammalian X could allow the future identification of the sexdetermining gene in lacertids. Promising candidates might be genes homologous to Sox3 as in therian mammals and the fish Oryzias dancena (Takehana et al, 2014), or an androgen receptor, the alleles of which play a role in the sex determination of the Japanese frog Rana rugosa (Fujii et al, 2014). Candidates for the sex-determining gene in lacertids might also be found in the part of the lacertid Z chromosome homologous to GGA17.…”

Sex Reversal in Amphibians

“…Its expression is upregulated in the male gonad and was proposed as a candidate gene for testis differentiation [Yokoyama et al, 2009]. A recent study has shown that Ar is involved in male sex determination in G. rugosa [Fujii et al, 2014]. Indeed, a subset of transgenic female (ZW) frogs carrying an exogenous Z-Ar driven by the promoter region of both Z-Ar and Ef1α genes formed ovotestes.…”