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Genome-Wide Motif Statistics are Shaped by DNA Binding Proteins over Evolutionary Time Scales

机译:DNA结合蛋白在进化时间尺度上影响着基因组范围的母体统计

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The composition of a genome with respect to all possible short DNA motifs impacts the ability of DNA binding proteins to locate and bind their target sites. Since nonfunctional DNA binding can be detrimental to cellular functions and ultimately to organismal fitness, organisms could benefit from reducing the number of nonfunctional DNA binding sites genome wide. Using in?vitro measurements of binding affinities for a large collection of DNA binding proteins, in multiple species, we detect a significant global avoidance of weak binding sites in genomes. We demonstrate that the underlying evolutionary process leaves a distinct genomic hallmark in that similar words have correlated frequencies, a signal that we detect in all species across domains of life. We consider the possibility that natural selection against weak binding sites contributes to this process, and using an evolutionary model we show that the strength of selection needed to maintain global word compositions is on the order of point mutation rates. Likewise, we show that evolutionary mechanisms based on interference of protein-DNA binding with replication and mutational repair processes could yield similar results and operate with similar rates. On the basis of these modeling and bioinformatic results, we conclude that genome-wide word compositions have been molded by DNA binding proteins acting through tiny evolutionary steps over time scales spanning millions of generations.
机译:关于所有可能的短DNA基序的基因组组成影响DNA结合蛋白定位和结合其靶位的能力。由于非功能性DNA结合可能有害于细胞功能,并最终损害有机体适应性,因此有机体可受益于减少全基因组范围内的非功能性DNA结合位点的数量。使用体外测量的结合亲和力,可以检测多种物种中大量的DNA结合蛋白,从而检测到基因组中弱结合位点的全面避开。我们证明了潜在的进化过程留下了独特的基因组特征,因为相似的词具有相关的频率,这是我们在生命各个领域中检测到的所有信号。我们考虑了针对弱结合位点的自然选择有助于该过程的可能性,并且使用进化模型,我们证明了维持整体词组成所需的选择强度约为点突变率。同样,我们表明基于蛋白质-DNA结合干扰复制和突变修复过程的进化机制可以产生相似的结果,并以相似的速率运行。根据这些建模和生物信息学的结果,我们得出结论,DNA结合蛋白是由DNA结合蛋白模制而成的,这些蛋白通过跨越数百万代的时间尺度上的微小进化步骤起作用。

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