Two duplicated gsdf homeologs cooperatively regulate male differentiation by inhibiting cyp19a1a transcription in a hexaploid fish

  • PLoS Genet. 2022 Jun 29;18(6):e1010288. doi: 10.1371/journal.pgen.1010288.
Ming-Tao Wang  1  2 ,  Zhi Li  1  2 ,  Miao Ding  1  2 ,  Tian-Zi Yao  1  2 ,  Sheng Yang  1  2 ,  Xiao-Juan Zhang  1  2 ,  Chun Miao  1  2 ,  Wen-Xuan Du  1  2 ,  Qian Shi  1  2 ,  Shun Li  1  2 ,  Jie Mei  3 ,  Yang Wang  1  2 ,  Zhong-Wei Wang  1  2 ,  Li Zhou  1  2 ,  Xi-Yin Li  1  2 ,  Jian-Fang Gui  1  2
Affiliations
  • 1. State Key Laboratory of Freshwater Ecology and Biotechnology, Hubei Hongshan Laboratory, The Innovative Academy of Seed Design, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
  • 2. University of Chinese Academy of Sciences, Beijing, China.
  • 3. College of Fisheries, Huazhong Agricultural University, Wuhan, China.
PMID: 35767574 DOI: 10.1371/journal.pgen.1010288
Abstract

Although evolutionary fates and expression patterns of duplicated genes have been extensively investigated, how duplicated genes co-regulate a biological process in polyploids remains largely unknown. Here, we identified two gsdf (gonadal somatic cell-derived factor) homeologous genes (gsdf-A and gsdf-B) in hexaploid gibel carp (Carassius gibelio), wherein each homeolog contained three highly conserved alleles. Interestingly, gsdf-A and gsdf-B transcription were mainly activated by dmrt1-A (dsx- and mab-3-related transcription factor 1) and dmrt1-B, respectively. Loss of either gsdf-A or gsdf-B alone resulted in partial male-to-female sex reversal and loss of both caused complete sex reversal, which could be rescued by a nonsteroidal aromatase inhibitor. Compensatory expression of gsdf-A and gsdf-B was observed in gsdf-B and gsdf-A mutants, respectively. Subsequently, we determined that in tissue culture cells, Gsdf-A and Gsdf-B both interacted with Ncoa5 (nuclear receptor coactivator 5) and blocked Ncoa5 interaction with Rora (retinoic acid-related orphan receptor-alpha) to repress Rora/Ncoa5-induced activation of cyp19a1a (Cytochrome P450, family 19, subfamily A, polypeptide 1a). These findings illustrate that Gsdf-A and Gsdf-B can regulate male differentiation by inhibiting cyp19a1a transcription in hexaploid gibel carp and also reveal that Gsdf-A and Gsdf-B can interact with Ncoa5 to suppress cyp19a1a transcription in vitro. This study provides a typical case of cooperative mechanism of duplicated genes in polyploids and also sheds light on the conserved evolution of sex differentiation.

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