Large-scale turnover of functional transcription factor binding sites in Drosophila.
Large-scale turnover of functional transcription factor binding sites in Drosophila.
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DOI：
10.1371/journal.pcbi.0020130
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发表时间：
2006-10
影响因子：
4.3
通讯作者：
Eisen MB
中科院分区：
文献类型：
--
作者：
Moses AM;Pollard DA;Nix DA;Iyer VN;Li XY;Biggin MD;Eisen MB
功能性转录因子结合位点的获得和丢失被认为是顺式调控DNA和基因表达进化变化的主要来源。我们已经开发了一个进化模型来研究结合位点的更替，该模型使用多个序列比对来评估单个结合位点的进化约束，并沿着系统发育树绘制增益和损失事件。我们应用该模型研究黑腹果蝇转录因子Zeste结合位点的进化动力学，利用全基因组在体内（ChIP-chip）结合数据鉴定功能Zeste结合位点，并利用黑腹果蝇D. melanogaster、D. simulans、D. erecta和D. yakuba的基因组序列研究它们的进化。我们估计超过5%的功能Zeste结合位点是在黑腹龙系中获得的，或者是在其他谱系中丢失的。我们发现，与侧翼序列相比，zest结合区域具有较低的结合位点损失率和较高的结合位点增益率。最后，我们发现结合位点的增益和损失在黑腹龙脑中是不对称分布的，这与zeste反应性调控元件的获得和损失是一致的。了解DNA突变导致生物体形态和功能改变的方式是分子进化生物学的主要目标。基因表达的变化很久以前就被认为是进化多样性的一个来源，但直到最近几年，研究人员才描述了一些具体的案例，在这些案例中，DNA的变化导致了基因表达的差异，而基因表达的差异反过来又影响了形态。现在，人们的注意力已经转向了解这些序列变化是如何产生影响的，以及是否可以通过检查越来越多的可用基因组序列来发现更多的进化新颖性的例子。Moses等人专注于转录因子结合位点，DNA片段作为分子开关来打开和关闭基因。这些开关被组织成更大的单元，发挥分子计算机的作用，确保基因在需要的时间和地点被制造出来。Moses和他的同事引入了一套新的计算方法来研究这些更大的调节功能单位是如何进化的。虽然他们发现这些开关中的大多数保持固定，但有相当数量的开关因突变而产生或破坏，从而对塑造动物形态的进化力量产生了新的见解。
The gain and loss of functional transcription factor binding sites has been proposed as a major source of evolutionary change in cis-regulatory DNA and gene expression. We have developed an evolutionary model to study binding-site turnover that uses multiple sequence alignments to assess the evolutionary constraint on individual binding sites, and to map gain and loss events along a phylogenetic tree. We apply this model to study the evolutionary dynamics of binding sites of the Drosophila melanogaster transcription factor Zeste, using genome-wide in vivo (ChIP–chip) binding data to identify functional Zeste binding sites, and the genome sequences of D. melanogaster, D. simulans, D. erecta, and D. yakuba to study their evolution. We estimate that more than 5% of functional Zeste binding sites in D. melanogaster were gained along the D. melanogaster lineage or lost along one of the other lineages. We find that Zeste-bound regions have a reduced rate of binding-site loss and an increased rate of binding-site gain relative to flanking sequences. Finally, we show that binding-site gains and losses are asymmetrically distributed with respect to D. melanogaster, consistent with lineage-specific acquisition and loss of Zeste-responsive regulatory elements. Understanding the ways in which mutations in DNA result in alterations of an organism's form and function is a major goal of molecular evolutionary biology. Changes in gene expression were long-ago proposed as a source of evolutionary diversity, but it was only in the last few years that researchers described specific cases where identified changes in DNA cause differences in gene expression, which in turn affect morphology. Attention has now turned to understanding how such sequence changes produce their effect and whether additional examples of evolutionary novelty can be found by examining the growing number of available genome sequences. Moses et al. focus on transcription factor binding sites, pieces of DNA that serve as molecular switches to turn genes on and off. These switches are organized into larger units that function as molecular computers and ensure that genes are made when and where they are needed. Moses and colleagues introduce a set of new computational methods to study how these larger units of regulatory function evolve. While they find that most of these switches remain fixed in place, a substantial number are created or destroyed by mutations, yielding new insights into the evolutionary forces that shape animal morphology.
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影响因子：
12.3
作者：
Fay JC;McCullough HL;Sniegowski PD;Eisen MB
通讯作者：
Eisen MB
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64.5
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