Evolution acts on enhancer organization to fine-tune gradient threshold readouts.
Evolution acts on enhancer organization to fine-tune gradient threshold readouts.
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Evolution对增强器组织进行微调梯度阈值读数。
DOI：
10.1371/journal.pbio.0060263
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发表时间：
2008-11-04
期刊：
影响因子：
9.8
通讯作者：
Erives, Albert
中科院分区：
文献类型：
--
作者：
Crocker, Justin;Tamori, Yoichiro;Erives, Albert
阐明基因调控序列的进化规律是后生动物多样化研究的关键。因此，我们正在探索的结构和组织约束的监管序列，通过研究功能等效的顺式调控模块（CRM），已在几个位点平行发展。这样一个独立的数据集允许多基因座研究，不受非功能性或限制性同源性的阻碍。黑腹果蝇的神经源性外胚层增强子（neurogenic ectoderm enhancers，NEE）就是这样一类协调调节的CRMs。NEE共享一个共同的结合位点组织，作为一个集合，将有助于研究CRM组织和CRM活动之间的关系，跨越不断发展的谱系。我们使用D。黑腹果蝇转基因系统，以筛选来自不同果蝇物种的NEE的功能适应。我们表明，在任何一个血统的基因组中的各个NEE模块独立进化的适应，以弥补特定的谱系发育和/或基因组的变化。具体来说，我们表明，网站组成和网站组织的NEE已微调不同的，特定的选择压力，在每一个不同的物种，我们已经研究：D。melanogaster、黑腹杜父鱼D. pseudobscura和D.男子气概此外，通过精确地改变组织的NEE与不同的形态梯度阈值读数，我们表明，CRM组织的演变是足以解释增强子活性的变化。因此，进化可以作用于CRM组织以在宽动态范围内微调形态发生基梯度阈值读数。我们的研究表明，等价类的标准物质是检测基因调控序列的谱系特异性适应的有力工具。基因的调节控制允许生物体在其全身产生多种细胞类型。基因调控涉及称为转录增强子的专门DNA序列，其在特定的地点和时间增加基因的表达。增强子包含由DNA结合蛋白唯一识别的特定DNA序列簇，其活性也在空间和时间上受到调节。DNA增强子在单个生物体中产生细胞类型多样性的关键作用表明，这些DNA序列的变化也可能是进化产生的生物体形式多样性的基础。然而，很少有例子连接增强子序列的功能适应的具体变化已被记录。我们研究了一组神经胚胎增强子，这些增强子在不同的果蝇物种中开启了一组特定的基因，这些果蝇物种已经彼此分离了2.5亿年。每个物种都经历了其蛋白质编码序列，基因调控序列，卵形态和发育时间的独特变化。我们发现，这些增强子中的蛋白质结合位点之间的组织间距已经以与补偿每个物种的动态和特异性进化历史的功能适应一致的方式进化。表征位于threeDrosophila物种的基因组中的神经外胚层增强子揭示了每个增强子进化的功能适应，以补偿每个谱系特有的进化变化。
The elucidation of principles governing evolution of gene regulatory sequence is critical to the study of metazoan diversification. We are therefore exploring the structure and organizational constraints of regulatory sequences by studying functionally equivalent cis-regulatory modules (CRMs) that have been evolving in parallel across several loci. Such an independent dataset allows a multi-locus study that is not hampered by nonfunctional or constrained homology. The neurogenic ectoderm enhancers (NEEs) of Drosophila melanogaster are one such class of coordinately regulated CRMs. The NEEs share a common organization of binding sites and as a set would be useful to study the relationship between CRM organization and CRM activity across evolving lineages. We used the D. melanogaster transgenic system to screen for functional adaptations in the NEEs from divergent drosophilid species. We show that the individual NEE modules across a genome in any one lineage have independently evolved adaptations to compensate for lineage-specific developmental and/or genomic changes. Specifically, we show that both the site composition and the site organization of NEEs have been finely tuned by distinct, lineage-specific selection pressures in each of the three divergent species that we have examined: D. melanogaster, D. pseudoobscura, and D. virilis. Furthermore, by precisely altering the organization of NEEs with different morphogen gradient threshold readouts, we show that CRM organizational evolution is sufficient for explaining changes in enhancer activity. Thus, evolution can act on CRM organization to fine-tune morphogen gradient threshold readouts over a wide dynamic range. Our study demonstrates that equivalence classes of CRMs are powerful tools for detecting lineage-specific adaptations by gene regulatory sequences. The regulatory control of genes allows an organism to generate a diversity of cell types throughout its body. Gene regulation involves specialized DNA sequences called transcriptional enhancers that increase the expression of genes in specific places and times. Enhancers contain clusters of specific DNA sequences that are uniquely recognized by DNA binding proteins, whose activities are also regulated in space and time. The critical role that DNA enhancers play in generating the diversity of cell types within a single organism suggests that changes in these DNA sequences may also underlie the diversity of organismal forms produced by evolution. However, few examples linking specific changes in enhancer sequences to functional adaptations have been documented. We studied a group of neuro-embryonic enhancers that turn on a certain group of genes in different fruit fly species that have been diverging from each other for ∼50 million years. Each species has experienced unique changes in its protein-coding sequences, gene regulatory sequences, egg morphology, and developmental timing. We found that the organizational spacing between the protein binding sites in these enhancers has evolved in a manner that is consistent with functional adaptations compensating for the dynamic and idiosyncratic evolutionary history of each species. Characterizing neuroectodermal enhancers located throughout the genomes of threeDrosophila species reveals that each enhancer evolved functional adaptations that compensate for the evolutionary changes specific to each lineage.
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影响因子：
64.8
作者：
Clark, Andrew G.;Eisen, Michael B.;MacCallum, Iain
通讯作者：
MacCallum, Iain
DOI：
10.1073/pnas.0509483102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Gregor, T;Bialek, W;Wieschaus, EF
通讯作者：
Wieschaus, EF
种群基因组学：果蝇果蝇中多态性和差异的全基因组分析。
影响因子：
9.8
作者：
Begun, David J.;Holloway, Alisha K.;Stevens, Kristian;Hillier, LaDeana W.;Poh, Yu-Ping;Hahn, Matthew W.;Nista, Phillip M.;Jones, Corbin D.;Kern, Andrew D.;Dewey, Colin N.;Pachter, Lior;Myers, Eugene;Langley, Charles H.
通讯作者：
Langley, Charles H.
两个层面的进化：基因和形态。
影响因子：
9.8
作者：
Carroll, SB
通讯作者：
Carroll, SB
影响因子：
9.8
作者：
Gasch AP;Moses AM;Chiang DY;Fraser HB;Berardini M;Eisen MB
通讯作者：
Eisen MB