Characterization and predictive discovery of evolutionarily conserved mammalian alternative promoters
Characterization and predictive discovery of evolutionarily conserved mammalian alternative promoters
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DOI：
10.1101/gr.5872707
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发表时间：
2007-02-01
期刊：
影响因子：
7
通讯作者：
Green, Phil
中科院分区：
文献类型：
--
作者：
Baek, Daehyun;Davis, Colleen;Green, Phil
最近的研究表明，许多哺乳动物基因具有替代启动子（APS）。但是，它们的生物学作用以及将它们与单个启动子（SP）区分开的特征仍然知之甚少。我们构建了大量的进化保守启动子的数据集，并将其用于识别序列特征，功能关联和表达模式，这些模式因启动子类型而有所不同。四个启动子类别富含CpG的AP，CpG贫困的AP，富含CpG的SPS和CPG贫乏的SP均显示序列保守的特征强度和模式，推定的转录相关基序的频率以及组织和组织和发育阶段表达偏好。与富含CpG的启动子相比，AP显示出比SPS和CPG贫困启动子的序列保守性要高得多。在CPG贫乏的启动子中，AN和SPS显示出截然不同的发展阶段偏好和TATA盒子频率。我们开发了一个鉴别器来预测启动子类型，通过实验测试验证了其精度，该测试结合了一种新型的反浏览混合序列轨迹，并使用它来找到几种新的歧视剂预测，所有哺乳动物基因中几乎一半的哺乳动物基因都具有进化保存的APS。 AP的这种高频率以及坚固的纯化选择维持它们，这意味着在扩展哺乳动物基因组的表达多样性中至关重要的作用。
Recent studies suggest that surprisingly many mammalian genes have alternative promoters (APs); however, their biological roles, and the characteristics that distinguish them from single promoters (SPs), remain poorly understood. We constructed a large data set of evolutionarily conserved promoters, and used it to identify sequence features, functional associations, and expression patterns that differ by promoter type. The four promoter categories CpG-rich APs, CpG-poor APs, CpG-rich SPs, and CpG-poor SPs each show characteristic strengths and patterns of sequence conservation, frequencies of putative transcription-related motifs, and tissue and developmental stage expression preferences. APs display substantially higher sequence conservation than SPs and CpG-poor promoters than CpG-rich promoters. Among CpG-poor promoters, AN and SPs show sharply contrasting developmental stage preferences and TATA box frequencies. We developed a discriminator to computationally predict promoter type, verified its accuracy through experimental tests that incorporate a novel method for deconvolving mixed sequence traces, and used it to find several new AN The discriminator predicts that almost half of all mammalian genes have evolutionarily conserved APs. This high frequency of APs, together with the strong purifying selection maintaining them, implies a crucial role in expanding the expression diversity of the mammalian genome.