Evolution of master sex determiners: TGF-β signalling pathways at regulatory crossroads

Abstract

To date, more than 20 different vertebrate master sex-determining genes have been identified on different sex chromosomes of mammals, birds, frogs and fish. Interestingly, six of these genes are transcription factors ( Dmrt1 - or Sox3 - related) and 13 others belong to the TGF-β signalling pathway ( Amh , Amhr2 , Bmpr1b , Gsdf and Gdf6 ). This pattern suggests that only a limited group of factors/signalling pathways are prone to become top regulators again and again. Although being clearly a subordinate member of the sex-regulatory network in mammals, the TGF-β signalling pathway made it to the top recurrently and independently. Facing this rolling wave of TGF-β signalling pathways, this review will decipher how the TGF-β signalling pathways cope with the canonical sex gene regulatory network and challenge the current evolutionary concepts accounting for the diversity of sex-determining mechanisms. This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.

Multiple sex chromosomes in teleost fishes from a cytogenetic perspective: state of the art and future challenges

“…However, the results gathered so far, especially in ranid frogs, provided no support for the theoretical role of sexually antagonistic genes in the evolutionary dynamics of sex chromosomes [ 141 , 142 ]. Alternatively, different genes involved in the sex-determining pathway can take over the role of the MSD gene and give rise to new sex chromosomes [ 47 , 143 , 144 ]. Indeed, a handful of genes are being repeatedly co-opted as MSD in fishes [ 10 , 123 , 143 , 144 ] and thus may contribute to the repeated use of the same linkage groups as sex chromosomes.…”

“…Alternatively, different genes involved in the sex-determining pathway can take over the role of the MSD gene and give rise to new sex chromosomes [ 47 , 143 , 144 ]. Indeed, a handful of genes are being repeatedly co-opted as MSD in fishes [ 10 , 123 , 143 , 144 ] and thus may contribute to the repeated use of the same linkage groups as sex chromosomes.…”

Expanding the classical paradigm: what we have learnt from vertebrates about sex chromosome evolution

“…A sex-determining locus mostly evolves as a new paralog (via duplication), or by allele differentiation. Both pathways are almost equally likely in vertebrates [ 86 ]. As alleles at a sex-determining locus can differ minimally—in an extreme case, only by a single nucleotide [ 87 ]—one can assume that the evolution of a novel sex-determining locus can be very easy and a minor genetic change appears sufficient for a major turnover in sex determination [ 11 ].…”

The replaceable master of sex determination: bottom-up hypothesis revisited

“…BMP4 has an important role in primordial germ cell differentiation, and treatments of epiblast-derived stem cells with this factor resulted in specification into germ cells [65]. In addition, other closely related genes like Gdf9 and Bmp15 are important in ovarian development of mammals and fish [66][67][68] (table 1).…”