Genome-wide regulatory complexity in yeast promoters: Separation of functionally conserved and neutral sequence
Genome-wide regulatory complexity in yeast promoters: Separation of functionally conserved and neutral sequence
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DOI：
10.1101/gr.3243305
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发表时间：
2005-02-01
期刊：
影响因子：
7
通讯作者：
Li, H
中科院分区：
文献类型：
--
作者：
Chin, CS;Chuang, JH;Li, H
为了衡量酵母中基因调控的复杂性，有必要了解有多少启动子序列发挥作用。跨物种的保护可以是检测功能序列的敏感手段，只要用局部中性突变率准确校准保护调用的重要性。通过分析酵母编码和启动子序列，我们发现酵母的中性突变率在整个基因组范围内是一致的，而哺乳动物则相反，哺乳动物中的中性突变率沿着染色体变化。我们开发了一种方法，使用这种统一的速率来估计纯化选择下启动子序列的数量。该量类似于 30%，相当于典型启动子的大约 90 bp。此外，使用隐马尔可夫模型，我们能够将每个启动子分为不同的高保守区和低保守区。已知的调控基序强烈偏向于高保护区，而低保护区的突变率与中性背景相似。某些基因本体论分组（例如碳水化合物代谢）具有大量高度保守的序列，表明其转录调控的复杂性。其他的（例如 RNA 加工）几乎没有高度保守的序列，并且很可能受到简单的调控。功能保守序列与中性背景的分离使 LIS 能够估计基因组规模上顺式调控的复杂性。
To gauge the complexity of gene regulation in yeast, it is essential to know how much promoter sequence is functional. Conservation across species can be a sensitive means of detecting functional sequences, provided that the significance of conservation call be accurately calibrated with the local neutral Mutation rate. By analyzing yeast coding and promoter sequences, we find that neutral mutation rates in yeast are uniform genome-wide, in contrast to mammals, where neutral mutation rates vary along chromosomes. We develop an approach that uses this uniform rate to estimate the amount of promoter sequence under purifying selection. This amount is similar to30%, corresponding to roughly 90 bp for a typical promoter. Furthermore, using a hidden Markov model, we are able to separate each promoter into distinct high and low conservation regions. Known regulatory motifs are strongly biased toward high conservation regions, while low conservation regions have Mutation rates similar to that of the neutral background. Certain Gene Ontology groupings of genes (e.g., Carbohydrate Metabolism) have large amounts of high conservation sequence, Suggesting complexity in their transcriptional regulation. Others (e.g., RNA Processing) have little high conservation sequence and are likely to be simply regulated. The separation of functionally conserved sequence from the neutral background allows LIS to estimate the complexity of cis-regulation on a genomic scale.