The unusual rainbow trout sex determination gene hijacked the canonical vertebrate gonadal differentiation pathway
The unusual rainbow trout sex determination gene hijacked the canonical vertebrate gonadal differentiation pathway
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DOI：
10.1073/pnas.1803826115
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发表时间：
2018-12-11
影响因子：
11.1
通讯作者：
Guiguen, Yann
中科院分区：
文献类型：
--
作者：
Bertho, Sylvain;Herpin, Amaury;Guiguen, Yann
进化的新颖性需要转录网络的重新布线和/或新的基因功能的进化。性别决定（SD）是最具可塑性的进化过程之一，需要这样的新奇。对脊椎动物SD进化的研究表明，新的SD主基因通常是从下游SD调控遗传网络中招募的基因。目前已知的脊椎动物中只有一个例外：鲑鱼主SD基因（sdY）的有趣案例，它源于一种免疫相关基因的复制。这一例外立即提出了一个问题：一个经典性别分化级联之外的基因是如何获得其作为男性SD基因的功能的？在这里，我们发现SdY通过与雌性决定转录因子Foxl2的叉头盒结构域相互作用而被整合到经典的脊椎动物性别分化级联中。在Foxl2存在的情况下，SdY被转移到细胞核中，在那里SdY: Foxl2复合物阻止芳香化酶（cyp19a1a）启动子与Nr5a1 （Sf1）合作激活。因此，通过阻断早期分化性腺中雌激素合成所需的正循环调节，SdY破坏了预设的雌性分化途径，从而使睾丸分化继续进行。这些结果还表明，从经典途径（如sdY）之外招募的不寻常的脊椎动物主性别决定基因的进化受到它们与典型性腺分化途径相互作用的能力的强烈限制。
Evolutionary novelties require rewiring of transcriptional networks and/or the evolution of new gene functions. Sex determination (SD), one of the most plastic evolutionary processes, requires such novelties. Studies on the evolution of vertebrate SD revealed that new master SD genes are generally recruited from genes involved in the downstream SD regulatory genetic network. Only a single exception to this rule is currently known in vertebrates: the intriguing case of the salmonid master SD gene (sdY), which arose from duplication of an immune-related gene. This exception immediately posed the question of how a gene outside from the classical sex differentiation cascade could acquire its function as a male SD gene. Here we show that SdY became integrated in the classical vertebrate sex differentiation cascade by interacting with the Forkhead box domain of the female-determining transcription factor, Foxl2. In the presence of Foxl2, SdY is translocated to the nucleus where the SdY: Foxl2 complex prevents activation of the aromatase (cyp19a1a) promoter in cooperation with Nr5a1 (Sf1). Hence, by blocking a positive loop of regulation needed for the synthesis of estrogens in the early differentiating gonad, SdY disrupts a preset female differentiation pathway, consequently allowing testicular differentiation to proceed. These results also suggest that the evolution of unusual vertebrate master sex determination genes recruited from outside the classical pathway like sdY is strongly constrained by their ability to interact with the canonical gonadal differentiation pathway.