Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation (Q6723287)

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