Plant Physiol:中科院植物所孔宏智研究组揭示重复基因表达分化分
2016年4月5日，国际植物学顶级期刊《plant Physiology》杂志上在线发表中国科学院植物研究所孔宏智研究组的一篇研究论文，研究人员以拟南芥中的APETALA1(AP1)和CAULIFLOWER(CAL)基因为例，对重复基因表达分化的模式、过程和机制进行了研究。孔宏智研究组博士生叶玲玲和博士毕业生王斌为该论文的并列第一作者，孔宏智研究员为论文通讯作者之一。
表达模式是基因的基本属性，了解基因表达模式在进化中的改变及其分子机制是进化生物学研究的重要内容。然而，由于表达模式本身是个非常复杂的概念，前人对其进化分子机制的研究尚不深入，典型的例子并不多见。
研究人员发现，作为一对由基因组加倍事件产生的重复基因，AP1和CAL在表达的时、空、量上均有差异，而且这些差异与其调控区一些转录因子结合位点的存在与否有关。在众多的转录因子结合位点中，AP1调控区的一个CArG box是导致两个基因表达分化的重要原因——由于该位点的存在，AP1既能自调控、又能被CAL调控，从而使AP1能够长时间维持较高的表达水平。通过进化分析，研究人员发现AP1的这个自调控位点是在拟南芥和琴叶拟南芥的最近共同祖先中获得的，是对祖先基因中个别碱基的修饰。研究还发现，AP1和CAL在调控元件上的差异是逐渐积累的，前者在保留祖先所有转录因子结合位点的同时获得了新的调控元件，而后者在进化的早期就丢失了多个转录因子结合位点。
该研究结果不仅阐明了AP1和CAL表达分化的分子机制，而且揭示了调控元件和表达模式进化的过程和特点。特别值得一提的是，该研究表明重复基因的表达分化其实是一个非常复杂的动态过程，不能用简单的经验模型来解释。研究结果对于理解基因表达进化的模式和机制具有重要意义，同时为深入理解重复基因的表达分化提供了新的思路。
AP1自调控位点(CArG box)的起源和功能。(A)CArG box序列的进化。(B)EMSA实验检测荠菜CruAP1和CruCAL的结合能力。(C)AP1与CruAP1表达量的比较。(D)AP1和CAL表达分化的示意图。(E)自调控位点的获得对二者表达分化贡献的模型。
原文链接：
Gain of An Auto-regulatory Site Led to Divergence of the Arabidopsis APETALA1 and CAULIFLOWER Duplicate Genes in the Time, Space and Level of expression and Regulation of One Paralog by the Other
原文摘要：
How genes change their expression patterns over time is still poorly understood. Here, by conducting expression, functional, bioinformatic and evolutionary analyses, we demonstrate that the differences between the Arabidopsis thaliana APETALA1 (AP1) and CAULIFLOWER (CAL) duplicate genes in the time, space and level of expression were determined by presence or absence of functionally important transcription factor-binding sites (TFBSs) in regulatory regions. In particular, a CArG box, which is the auto-regulatory site of AP1 that can also be bound by the CAL protein, is a key determinant of the expression differences. Because of the CArG box, AP1 is both auto- and cross-regulated (by AP1 and CAL, respectively), and its relatively high-level expression is maintained till to near-mature sepals and petals. The observation that the CArG box was gained recently further suggests that the auto- and cross-regulation of AP1, as well as its function in sepal and petal development, is a derived feature. By comparing the evolutionary histories of this and other TFBSs, we further indicate that the divergence of AP1 and CAL in regulatory regions has been markedly asymmetric and can be divided into several stages. Specifically, shortly after duplication, when AP1 happened to be the paralog that maintained the function of the ancestral gene, CAL experienced certain degrees of degenerate evolution, in which several functionally important TFBSs were lost. Later, when functional divergence allowed survival of both paralogs, CAL remained largely unchanged in expression whereas the functions of AP1 were gradually reinforced by gains of the CArG-box and other TFBSs.
作者：孔宏智
