ncDNA and drift drive binding site accumulation.
ncDNA and drift drive binding site accumulation.
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DOI：
10.1186/1471-2148-12-159
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发表时间：
2012-08-30
影响因子：
3.4
通讯作者：
Nakhleh L
中科院分区：
文献类型：
--
作者：
Ruths T;Nakhleh L
转录因子结合位点（TFBS）在生物体基因组中的数量与生物体的调控网络的复杂性正相关。然而，TFBS在基因组中产生和积累的方式以及调控网络复杂性对生物体适应性的影响还远未可知。许多生物体TFBS数据的可用性为探索这些问题提供了机会，特别是从进化的角度。我们分析了五种模式生物的TFBS数据。coli K12、S.酿酒酵母C. elegans、D. melanogaster，黑腹果蝇A.并发现了有机体基因组中非编码DNA（ncDNA）的数量与调控复杂性之间的正相关。基于这一发现，我们假设，ncDNA的数量，结合种群大小，可以解释跨生物体的调控复杂性模式。为了验证这一假设，我们设计了一个基于基因组的调控途径模型，并通过群体遗传模拟将其置于进化的力量下。研究结果支持了我们的假设，表明只有中性进化力量才能解释TFBS模式，而对调节网络功能的选择并没有改变这一发现。顺式正则组并不是一个单纯由适应力构建的干净的函数网络，而是一个充满了非适应力噪声的数据源。从调控的角度来看，这种进化噪声表现为结合位点和途径水平上的复杂性，这对微生物学、遗传学和合成生物学的许多方向都有重要意义。
The amount of transcription factor binding sites (TFBS) in an organism’s genome positively correlates with the complexity of the regulatory network of the organism. However, the manner by which TFBS arise and accumulate in genomes and the effects of regulatory network complexity on the organism’s fitness are far from being known. The availability of TFBS data from many organisms provides an opportunity to explore these issues, particularly from an evolutionary perspective. We analyzed TFBS data from five model organisms – E. coli K12, S. cerevisiae, C. elegans, D. melanogaster, A. thaliana – and found a positive correlation between the amount of non-coding DNA (ncDNA) in the organism’s genome and regulatory complexity. Based on this finding, we hypothesize that the amount of ncDNA, combined with the population size, can explain the patterns of regulatory complexity across organisms. To test this hypothesis, we devised a genome-based regulatory pathway model and subjected it to the forces of evolution through population genetic simulations. The results support our hypothesis, showing neutral evolutionary forces alone can explain TFBS patterns, and that selection on the regulatory network function does not alter this finding. The cis-regulome is not a clean functional network crafted by adaptive forces alone, but instead a data source filled with the noise of non-adaptive forces. From a regulatory perspective, this evolutionary noise manifests as complexity on both the binding site and pathway level, which has significant implications on many directions in microbiology, genetics, and synthetic biology.
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