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Reduced activity of SRY and its target enhancer Sox9-TESCO in a mouse species with X∗Y sex reversal

机译:X ∗ ​​Y性别反转的小鼠物种中SRY及其靶增强子Sox9-TESCO的活性降低

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摘要

In most eutherian mammals, sex determination is governed by the Y-linked gene Sry, but in African pygmy mice Mus minutoides, Sry action is overridden by a variant X chromosome (X*), yielding X*Y females. We hypothesized that X*Y sex reversal may be underpinned not only by neomorphic X chromosome functionality, but also by a compromised Sry pathway. Here, we show that neither M. minutoides SRY nor its target, the Sox9-TESCO enhancer, had appreciable transcriptional activity in in vitro assays, correlating with sequence degradation compared to Mus musculus counterparts. However, M. minutoides SRY activated its cognate TESCO to a moderate degree, and can clearly engage the male pathway in M. minutoides in the wild, indicating that SRY and TESCO may have co-evolved in M. minutoides to retain function above a threshold level. We suggest that weakening of the SRY/TESCO nexus may have facilitated the rise and spread of a variant X* chromosome carrying female-inducing modifier gene(s).
机译:在大多数欧亚哺乳动物中,性别决定是由Y连锁基因Sry决定的,但在非洲侏儒鼠Minutoides中,Sry的作用被X染色体变异(X *)覆盖,从而产生X * Y雌性。我们假设X * Y性逆转不仅可以由新形X染色体功能来支撑,而且可以由受损的Sry途径来支撑。在这里,我们显示在体外测定中,无论是小分枝杆菌SRY还是其靶标Sox9-TESCO增强子都没有明显的转录活性,与小家鼠对应的序列降解相关。但是,米诺德氏菌SRY激活了其同源的TESCO,并可以在野生环境中明显参与米诺德氏菌的雄性途径,这表明SRY和TESCO可能在米诺德氏菌中共同进化,以保持功能高于阈值。水平。我们建议SRY / TESCO关系的减弱可能已经促进了携带雌性诱导修饰基因的X *变异染色体的上升和传播。

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