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

Abstract

Different group of vertebrates and invertebrates demonstrate an amazing diversity of gene regulations not only at the top but also at the bottom of the sex determination genetic network. As early as 1995, based on emerging findings in Drosophila melanogaster and Caenorhabditis elegans, Wilkins suggested that the evolution of the sex determination pathway evolved from the bottom to the top of the hierarchy. Based on our current knowledge, this review revisits the 'bottom-up' hypothesis and applies its logic to vertebrates. The basic operation of the determination network is through the dynamics of the opposing male and female pathways together with a persistent need to maintain the sexual identity of the cells of the gonad up to the reproductive stage in adults. The sex-determining trigger circumstantially acts from outside the genetic network, but the regulatory network is not built around it as a main node, thus maintaining the genetic structure of the network. New sex-promoting genes arise either through allelic diversification or gene duplication and act specially at the sex-determination period, without integration into the complete network. Due to this peripheral position the new regulator is not an indispensable component of the sex-determining network and can be easily replaced. 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)'.

Keywords: bottom-up; master gene; sex determination; vertebrate.

Figure 1.

Hypothetical source and interaction between the sex-determining trigger and the sex determination pathway. Genes involved in the development of one of the sexes also perform a role in repressing the opposite pathway. The sex-determining trigger can be genetic (GSD) or environmental (ESD), and it acts in promoting or repressing the male (blue) or the female (red) pathway. The genetic sex-determining trigger originates (black arrows) from genes of the already established sex-determination pathway, or even from genetic pathways unrelated to sex.

Figure 2.

Model for a spatial-temporal influence of the sex-promoting signal on the sex-determination genetic network. Main genetic factors are expressed in the bipotential gonad and the sex-promoting signal acts outside of the network, leading the gonad to differentiate towards testis or ovary. The pool of genes involved in the network is maintained in the differentiated gonad, but their relative importance changes depending on the outcome of the determination phase. Genes with higher expression in testis are classically named ‘male-related genes’ (dark blue) and genes with higher expression in ovaries are called ‘female-related’ genes (dark red), but their role is not restricted only to one sex. In the example, a male sex-determining (SD) gene increases the activity (blue arrow) of amh unbalancing the network to develop towards male. The same principle can be observed for environmental cues, that could, for instance, induce the female pathway by blocking important male factors such as dmrt1, or by activating female drivers such as estrogen receptor (Esr1).