Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation
| Autor: | 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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| Rok vydání: | 2022 |
| Předmět: |
Male
Models Molecular endocrine system Protein Conformation RNA Splicing Gene Dosage Molecular Conformation nr5a1 Steroidogenic Factor 1 Chromosomes sex-specific splicing chromosome conformation Structure-Activity Relationship Sex Factors reptile sex determination Genetics Animals Amino Acid Sequence Alleles Uncategorized Sex Chromosomes Multidisciplinary Reptiles Lizards Biological Sciences Sex Determination Processes Female |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2116475119 |
| Popis: | Significance Reptiles have an extraordinary variety of mechanisms to determine sex. The best candidate sex-determining gene in our model reptile (the Australian central bearded dragon) is the key vertebrate sex gene nr5a1 (coding for the steroidogenic factor 1). There are no sex-specific sequence differences between nr5a1 alleles on the sex chromosomes, but the Z- and W-borne alleles are transcribed into remarkably different alternative transcripts. We propose that altered configuration of the repeat-laden W chromosome affects the conformation of the primary transcript to generate more diverse and potentially inhibitory W-borne isoforms that suppress testis determination. This is a mechanism for vertebrate sex determination, in which epigenetic control regulates the action of a gene present on both sex chromosomes. 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. |
| Databáze: | OpenAIRE |
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