Sex determination without sex chromosomes

Abstract

With or without sex chromosomes, sex determination is a synthesis of many molecular events that drives a community of cells towards a coordinated tissue fate. In this review, we will consider how a sex determination pathway can be engaged and stabilized without an inherited genetic determinant. In many reptilian species, no sex chromosomes have been identified, yet a conserved network of gene expression is initiated. Recent studies propose that epigenetic regulation mediates the effects of temperature on these genes through dynamic post-transcriptional, post-translational and metabolic pathways. It is likely that there is no singular regulator of sex determination, but rather an accumulation of molecular events that shift the scales towards one fate over another until a threshold is reached sufficient to maintain and stabilize one pathway and repress the alternative pathway. Investigations into the mechanism underlying sex determination without sex chromosomes should focus on cellular processes that are frequently activated by multiple stimuli or can synthesize multiple inputs and drive a coordinated response. 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: environmental sex determination; epigenetics; temperature-dependent sex determination.

Figure 1.

Environmental sex determination (ESD) has evolved repeatedly in multiple vertebrate lineages. Multiple sex determining systems can operate simultaneously. Specific examples discussed in this review are indicated by an animal icon. We have broken the Squamates node (indicated by an asterisk) into lizards and snakes to highlight the observation that while ESD has evolved multiple times in many lizard species, this phenomena has not yet been described in snakes. Adapted from [1] and [2].

Figure 2.

Sex determination is a cumulative process. Female- and male-sex determination pathways are initiated in the bipotential gonad and are maintained over the course of multiple embryonic stages until ovary or testis fate is stabilized. Proposed mechanisms of sex determination in the red-eared slider turtle T. scripta are diagrammed in relation to onset of expression per Greenbaum embryonic stage [8].

Figure 3.

Sex determination is a complex synthesis of many molecular events. Without sex chromosomes, initiation and stabilization of sexual fate probably involves post-transcriptional, post-translational and metabolic pathways that affect gene regulatory events. An accumulation of molecular events will be sufficient to maintain and stabilize one pathway and repress the alternative pathway. Here, we show how many environmental pathways converge upon STAT3 activation, which critically regulates epigenetic activation of male gene expression. Grey boxes with numbers refer to the Reference list.