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

Xiuwen Zhang, Susan Wagner, Clare E Holleley, Janine E Deakin, Kazumi Matsubara, Ira W Deveson, Denis O'Meally, Hardip R Patel, Tariq Ezaz, Zhao Li, Chexu Wang, Melanie Edwards, Jennifer A Marshall Graves, Arthur Georges

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Pogona vitticeps has female heterogamety (ZZ/ZW), but the master sex-determining gene is unknown, as it is for all reptiles. We show that nr5a1 (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-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 16 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 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 P. vitticeps is a W-borne dominant female-determining gene that may be controlled epigenetically.

Original languageEnglish
Article numbere2116475119
Pages (from-to)1-9
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
Publication statusPublished - 25 Jan 2022


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