Functional tests of enhancer conservation between distantly related species
Functional tests of enhancer conservation between distantly related species
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DOI：
10.1242/dev.00711
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发表时间：
2003-11-01
期刊：
影响因子：
4.6
通讯作者：
Ruvkun, G
中科院分区：
文献类型：
--
作者：
Ruvinsky, I;Ruvkun, G
直向同源基因的表达模式通常是保守的，即使在远亲生物之间也是如此，这表明一旦建立，发育程序可以在很长一段进化时间内稳定地维持。因为许多正向转录因子在功能上也是保守的，所以解释同源基因表达模式的一个可能的模型是正向转录因子基因的顺式调节元件内的特异性结合位点的保守。如果这个模型是正确的，那么来自一个生物体的顺式调节元件将有望在一个远亲生物体中发挥作用。为了验证这一假设，我们融合了绿色荧光蛋白基因的神经元和肌肉增强子元件从各种果蝇基因，并测试这些是否会激活表达的同源细胞类型的秀丽隐杆线虫。来自几个基因的调控元件在同源组织类型中指导适当的表达，表明调控位点的保守性。然而，大多数果蝇基因测试的增强子没有正确识别在线虫，这意味着在这个进化的距离足够的变化发生在顺式调控序列和/或转录因子，以防止正确识别异源特异性增强子。比较了C. elegans和C. briggsae揭示了广泛的保守性，以及功能分歧的具体实例。我们的研究结果表明，顺式调控序列的功能变化积累的时间尺度远短于节肢动物和线虫的分歧，和机制以外的保护增强子元件内的个别结合位点负责保护远亲物种之间的同源基因的表达模式。
Expression patterns of orthologous genes are often conserved, even between distantly related organisms, suggesting that once established, developmental programs can be stably maintained over long periods of evolutionary time. Because many orthologous transcription factors are also functionally conserved, one possible model to account for homologous gene expression patterns, is conservation of specific binding sites within cis-regulatory elements of orthologous genes. If this model is correct, a cis-regulatory element from one organism would be expected to function in a distantly related organism. To test this hypothesis, we fused the green fluorescent protein gene to neuronal and muscular enhancer elements from a variety of Drosophila melanogaster genes, and tested whether these would activate expression in the homologous cell types in Caenorhabditis elegans. Regulatory elements from several genes directed appropriate expression in homologous tissue types, suggesting conservation of regulatory sites. However, enhancers of most Drosophila genes tested were not properly recognized in C elegans, implying that over this evolutionary distance enough changes occurred in cis-regulatory sequences and/or transcription factors to prevent proper recognition of heterospecific enhancers. Comparisons of enhancer elements of orthologous genes between C. elegans and C. briggsae revealed extensive conservation, as well as specific instances of functional divergence. Our results indicate that functional changes in cis-regulatory sequences accumulate on timescales much shorter than the divergence of arthropods and nematodes, and that mechanisms other than conservation of individual binding sites within enhancer elements are responsible for the conservation of expression patterns of homologous genes between distantly related species.