Opposite roles ofDMRT1and its W-linked paralogue,DM-W, in sexual dimorphism ofXenopus laevis: implications of a ZZ/ZW-type sex-determining system

Abstract

SUMMARYA Y-linked gene, DMY/dmrt1bY, in teleost fish medka and a Z-linked gene, DMRT1, in chicken are both required for male sex determination. We recently isolated a W-linked gene, DM-W, as a paralogue of DMRT1 in Xenopus laevis, which has a ZZ/ZW-type sex-determining system. The DNA-binding domain of DM-W shows high sequence identity with that of DMRT1, but DM-W has no significant sequence similarity with the transactivation domain of DMRT1. Here, we first show colocalization of DM-W and DMRT1 in the somatic cells surrounding primordial germ cells in ZW gonad during sex determination. We next examined characteristics of DM-W and DMRT1 as a transcription factor in vitro. DM-W and DMRT1 shared a DNA-binding sequence. Importantly, DM-W dose-dependently antagonized the transcriptional activity of DMRT1 on a DMRT1-driven luciferase reporter system in 293 cells. We also examined roles of DM-W or DMRT1 in gonadal formation. Some transgenic ZW tadpoles bearing a DM-W knockdown vector had gonads with a testicular structure, and two developed into frogs with testicular gonads. Ectopic DMRT1 induced primary testicular development in some ZW individuals. These observations indicated that DM-W and DMRT1 could have opposite functions in the sex determination. Our findings support a novel model for a ZZ/ZW-type system in which DM-W directs female sex as a sex-determining gene, by antagonizing DMRT1. Additionally, they suggest that DM-W diverged from DMRT1 as a dominant-negative type gene, i.e. as a 'neofunctionalization' gene for the ZZ/ZW-type system. Finally, we discuss a conserved role of DMRT1 in testis formation during vertebrate evolution.

Triploid plover female provides support for a role of the W chromosome in avian sex determination

“…This still unknown gene could antagonistically interact with DMRT1, for example, through changes of methylation patterns [1]. In amphibians with a ZW sex determination system, DM-W, a recently identified truncated paralogue of DMRT1 on the W chromosome, interacts antagonistically with DMRT1 and is known to trigger femaleness [19]. DM-W has no known homologue in chickens, although the current lack of sequence information for the W chromosome from other birds does not rule out the presence of a DMRT1 paralogue or other potentially female-determining genes in other avian lineages.…”

The genetic contribution to sex determination and number of sex chromosomes vary among populations of common frogs (Rana temporaria)

“…The former is thought to determine sex in birds (Smith et al, 2009), whereas paralogs play this role in species of fish and frogs (Matsuda et al, 2002;Nanda et al, 2002;Yoshimoto et al, 2010). The antiMullerian hormone Amh likely determines sex in platypus (Cortez et al, 2014), whereas a paralog has been shown to play this role in a fish (Hattori et al, 2012).…”

Rowley Review

“…Mammals with DMRT1 loss-of-function mutations have impaired testicular development (Raymond et al 2000;Õunap et al 2004). In lower vertebrates, a duplicated and diverged copy of DMRT1, called DMY/DMRT1bY, is the male determinant in the Medaka Fish (Oryzias latipes) (Matsuda et al 2002;Nanda et al 2002), whereas a truncated copy, called DMW, antagonises DMRT1 function and participates in ovarian determinant in the African Clawed Frog (Xenopus laevis) (Yoshimoto et al 2008(Yoshimoto et al , 2010. Hence, this gene and its homologues clearly have a central role in vertebrate gonadal development.…”