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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Energy-dependent fitness: A quantitative model for the evolution of yeast transcription factor binding sites
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Energy-dependent fitness: A quantitative model for the evolution of yeast transcription factor binding sites

机译：能量依赖性适应性：酵母转录因子结合位点进化的定量模型

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摘要

We present a genomewide cross-species analysis of regulation for broad-acting transcription factors in yeast. Our model for binding site evolution is founded on biophysics: the binding energy between transcription factor and site is a quantitative phenotype of regulatory function, and selection is given by a fitness landscape that depends on this phenotype. The model quantifies conservation, as well as loss and gain, of functional binding sites in a coherent way. Its predictions are supported by direct cross-species comparison between four yeast species. We find ubiquitous compensatory mutations within functional sites, such that the energy phenotype and the function of a site evolve in a significantly more constrained way than does its sequence. We also find evidence for substantial evolution of regulatory function involving point mutations as well as sequence insertions and deletions within binding sites. Genes lose their regulatory link to a given transcription factor at a rate similar to the neutral point mutation rate, from which we infer a moderate average fitness advantage of functional over nonfunctional sites. In a wider context, this study provides an example of inference of selection acting on a quantitative molecular trait.
机译：我们提出了对酵母中的广谱转录因子调控的全基因组跨物种分析。我们的结合位点进化模型基于生物物理学：转录因子和位点之间的结合能是调节功能的定量表型，选择取决于该表型的适应度。该模型以连贯的方式量化了功能性结合位点的保守性以及丢失和获得。它的预测得到了四种酵母菌种之间直接种间比较的支持。我们发现功能位点中普遍存在的补偿性突变，使得能量表型和位点的功能比其序列受约束的方式明显得多。我们还发现监管功能的重大演变的证据，涉及点突变以及结合位点内的序列插入和缺失。基因以与中性点突变率相似的速率失去与给定转录因子的调控联系，从中我们推断出功能性相对于非功能性位点的中等平均适应性优势。在更广泛的背景下，这项研究提供了一个推理实例，该推理作用于定量的分子性状。

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