A long‐standing problem in biology is how to dissect traits for which no tractable model exists. Here, we screen for genes like the nude locus (Foxn1)—genes central to mammalian hair and thymus development—using animals that never evolved hair, thymi, or Foxn1. Fruit flies are morphologically disrupted by the FOXN1 transcription factor and rescued by weak reductions in fly gene function, revealing molecules that potently synergize with FOXN1 to effect dramatic, chaotic change. Strong synergy/effectivity in flies is expected to reflect strong selection/functionality (purpose) in mammals; the more disruptive a molecular interaction is in alien contexts (flies), the more beneficial it will be in its natural, formative contexts (mammals). The approach identifies Aff4 as the first nude‐like locus, as murine AFF4 and FOXN1 cooperatively induce similar cutaneous/thymic phenotypes, similar gene expression programs, and the same step of transcription, pre‐initiation complex formation. These AFF4 functions are unexpected, as AFF4 also serves as a scaffold in common transcriptional‐elongation complexes. Most likely, the approach works because an interaction's power to disrupt is the inevitable consequence of its selected‐for power to benefit.

中文翻译：

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通过破坏和裸体基因座的选定合作伙伴进行建模

生物学中一个长期存在的问题是如何剖析没有易处理模型的特征。在这里，我们使用从未进化过毛发，胸腺或Foxn1的动物来筛选诸如裸基因座（Foxn1）等基因，这些基因是哺乳动物毛发和胸腺发育的核心基因。果蝇在形态上受到FOXN1转录因子的破坏，并通过果蝇基因功能的弱降低而得以拯救，从而揭示了与FOXN1有效协同作用的分子，从而产生了戏剧性的，混乱的变化。苍蝇具有很强的协同作用/功效，有望在哺乳动物中体现出强大的选择/功能（目的）；分子相互作用在外星环境（果蝇）中越具有破坏性，则在其自然，形成性环境（哺乳动物）中越有利。该方法可识别Aff4作为第一个类似裸鼠的基因座，鼠AFF4和FOXN1协同诱导相似的皮肤/胸腺表型，相似的基因表达程序以及相同的转录步骤，即启动复合物的形成。这些AFF4的功能是出乎意料的，因为AFF4在普通的转录延伸复合物中也起着支架的作用。这种方法之所以可行，是因为互动的破坏能力是其选择的获利能力的必然结果。