Sex-specific splicing of Z- and W-borne <i>nr5a1</i> 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, Li Zhao, Chexu Wang, Melanie Edwards, Jennifer A. Marshall Graves, Arthur Georges
Abstract
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.