Sex-specific splicing of Z- and W-borne <i>nr5a1</i> alleles suggests sex determination is controlled by chromosome conformation.

Abstract

<i>Pogona vitticeps</i> has female heterogamety (ZZ/ZW), but the master sex-determining gene is unknown, as it is for all reptiles. We show that <i>nr5a1</i> (Nuclear Receptor Subfamily 5 Group A Member 1), a gene that is essential in mammalian sex determination, has alleles on the Z and W chromosomes (Z-<i>nr5a1</i> and W-<i>nr5a1</i>), which are both expressed and can recombine. Three transcript isoforms of Z-<i>nr5a1</i> were detected in gonads of adult ZZ males, two of which encode a functional protein. However, ZW females produced 16 isoforms, most of which contained premature stop codons. The array of transcripts produced by the W-borne allele (W-<i>nr5a1</i>) is likely to produce truncated polypeptides that contain a structurally normal DNA-binding domain and could act as a competitive inhibitor to the full-length intact protein. We hypothesize that an altered configuration of the W chromosome affects the conformation of the primary transcript generating inhibitory W-borne isoforms that suppress testis determination. Under this hypothesis, the genetic sex determination (GSD) system of <i>P. vitticeps</i> is a W-borne dominant female-determining gene that may be controlled epigenetically.