Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213
Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):5854-5861. doi: 10.1073/pnas.1610611114.
Sea stars and sea urchins are model systems for interrogating the types of deep evolutionary changes that have restructured developmental gene regulatory networks (GRNs). Although -regulatory DNA evolution is likely the predominant mechanism of change, it was recently shown that Tbrain, a Tbox transcription factor protein, has evolved a changed preference for a low-affinity, secondary binding motif. The primary, high-affinity motif is conserved. To date, however, no genome-wide comparisons have been performed to provide an unbiased assessment of the evolution of GRNs between these taxa, and no study has attempted to determine the interplay between transcription factor binding motif evolution and GRN topology. The study here measures genome-wide binding of Tbrain orthologs by using ChIP-sequencing and associates these orthologs with putative target genes to assess global function. Targets of both factors are enriched for other regulatory genes, although nonoverlapping sets of functional enrichments in the two datasets suggest a much diverged function. The number of low-affinity binding motifs is significantly depressed in sea urchins compared with sea star, but both motif types are associated with genes from a range of functional categories. Only a small fraction (∼10%) of genes are predicted to be orthologous targets. Collectively, these data indicate that Tbr has evolved significantly different developmental roles in these echinoderms and that the targets and the binding motifs in associated -regulatory sequences are dispersed throughout the hierarchy of the GRN, rather than being biased toward terminal process or discrete functional blocks, which suggests extensive evolutionary tinkering.
海星和海胆是用于探究深度进化变化类型的模式系统，这些变化重构了发育基因调控网络（GRN）。虽然 - 调控 DNA 进化可能是主要的变化机制，但最近表明，Tbrain 是一种 T 盒转录因子蛋白，已经进化出对低亲和力、次要结合基序的改变偏好。主要的高亲和力基序是保守的。然而，迄今为止，尚未进行全基因组比较，以提供对这些分类群之间 GRN 进化的无偏评估，也没有研究试图确定转录因子结合基序进化与 GRN 拓扑结构之间的相互作用。本研究通过使用 ChIP-seq 测量了 Tbrain 同源物的全基因组结合，并将这些同源物与推定的靶基因相关联，以评估全局功能。这两个因素的靶标都富含其他调节基因，尽管两个数据集的非重叠功能富集集表明功能有很大差异。与海星相比，海胆中的低亲和力结合基序数量明显减少，但两种基序类型都与来自一系列功能类别的基因相关联。只有一小部分（约 10%）的基因被预测为直系同源靶基因。总的来说，这些数据表明，Tbr 在这两种棘皮动物中已经进化出了非常不同的发育作用，并且相关的 - 调控序列中的靶基因和结合基序分散在 GRN 的层次结构中，而不是偏向于终端过程或离散的功能块，这表明了广泛的进化 tinkering。
