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.
University of Chinese Academy of Sciences, Beijing, China.
PLoS Genet. 2022 Jun 29;18(6):e1010288. doi: 10.1371/journal.pgen.1010288. eCollection 2022 Jun.
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.
尽管已经广泛研究了重复基因的进化命运和表达模式，但多倍体中重复基因如何共同调控一个生物学过程仍知之甚少。在这里，我们在六倍体鲤鱼（Carassius gibelio）中鉴定了两个 gsdf（性腺体细胞衍生因子）同源基因（gsdf-A 和 gsdf-B），每个同源基因包含三个高度保守的等位基因。有趣的是，gsdf-A 和 gsdf-B 的转录主要分别被 dmrt1-A（dsx- 和 mab-3 相关转录因子 1）和 dmrt1-B 激活。单独缺失任一 gsdf-A 或 gsdf-B 会导致部分雄性到雌性的性反转，而缺失两者则会导致完全的性反转，这可以通过非甾体芳香化酶抑制剂来挽救。在 gsdf-B 和 gsdf-A 突变体中观察到 gsdf-A 和 gsdf-B 的代偿性表达。随后，我们确定在组织培养细胞中，Gsdf-A 和 Gsdf-B 都与 Ncoa5（核受体共激活因子 5）相互作用，并阻止 Ncoa5 与 Rora（维甲酸相关孤儿受体-α）相互作用，从而抑制 Rora/Ncoa5 诱导的 cyp19a1a（细胞色素 P450，家族 19，亚家族 A，多肽 1a）的激活。这些发现表明，Gsdf-A 和 Gsdf-B 可以通过抑制六倍体鲤鱼中 cyp19a1a 的转录来调节雄性分化，并且还揭示了 Gsdf-A 和 Gsdf-B 可以与 Ncoa5 相互作用以在体外抑制 cyp19a1a 的转录。这项研究提供了多倍体中重复基因协同作用机制的典型案例，也揭示了性别分化的保守进化。
