Evidence for stabilizing selection in a eukaryotic enhancer element
Evidence for stabilizing selection in a eukaryotic enhancer element
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DOI：
10.1038/35000615
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发表时间：
2000-02-03
期刊：
影响因子：
64.8
通讯作者：
Kreitman, M
中科院分区：
文献类型：
--
作者：
Ludwig, MZ;Bergman, C;Kreitman, M
真核基因的表达是由紧凑的顺式调控模块或增强子介导的，这些模块或增强子由特定的转录因子集结合(1)。这些结合的转录因子的组合相互作用决定了时间和组织特异性的基因激活或抑制。偶跳过的条纹2元件控制着偶跳过的信使RNA在果蝇胚胎中的第二横纹的表达，是真核细胞中最具特性的增强子之一(2-4)。虽然偶数跳过的条纹2在果蝇中的表达非常保守，但条纹2元件本身在其结合位点序列和它们之间的间距方面经历了相当大的进化变化。我们已经研究了这一明显的矛盾，在这里我们表明，两个嵌合体增强子，通过交换两个物种的天然条纹2元件的5‘和3’半构建，不再驱动报告基因在野生型模式中的表达。因此，物种之间的序列差异具有功能后果，但它们被其他共同进化的差异所掩盖。在这些结果的基础上，我们提出了真核生物调控序列进化的模型。
Eukaryotic gene expression is mediated by compact cis-regulatory modules, or enhancers, which are bound by specific sets of transcription factors(1). The combinatorial interaction of these bound transcription factors determines time- and tissue-specific gene activation or repression. The even-skipped stripe 2 element controls the expression of the second transverse stripe of a even-skipped messenger RNA in Drosophila melanogaster embryos, and is one of the best characterized eukaryotic enhancers(2-4). Although even-skipped stripe 2 expression is strongly conserved in Drosophila, the stripe 2 element itself has undergone considerable evolutionary change in its binding-site sequences and the spacing between them. We have investigated this apparent contradiction, and here we show that two chimaeric enhancers, constructed by swapping the 5' and 3' halves of the native stripe 2 elements of two species, no longer drive expression of a reporter gene in the wildtype pattern. Sequence differences between species have functional consequences, therefore, but they are masked by other coevolved differences. On the basis of these results, we present a model for the evolution of eukaryotic regulatory sequences.