期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：4
DOI：10.1073/pnas.2116475119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：enreptile sex determinationnr5a1chromosome conformationsex-specific splicing
