Cis-regulatory programs in the development and evolution of vertebrate paired appendages.
Cis-regulatory programs in the development and evolution of vertebrate paired appendages.
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DOI：
10.1016/j.semcdb.2016.01.015
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发表时间：
2016-09
影响因子：
7.3
通讯作者：
Shubin NH
中科院分区：
文献类型：
--
作者：
Gehrke AR;Shubin NH
差异基因表达是发育的核心，调节决定细胞特性所需的遗传变化。顺式作用元件(如增强子)对基因活性的调节是通过精确控制基因在胚胎空间和时间的表达来确定差异基因活性的关键机制。对调节区的修改可以对表型产生深远的影响，因此，发育和进化生物学家越来越重视阐明构建和形成身体计划的基因的转录控制。在这里，我们追溯了脊椎动物附肢发育的三个关键基因(Fgf8、Shh和HoxD/A)转录控制的进化历史。在这些调控模块内和整个调控模块中，我们发现既复杂又灵活的调控与更固定的增强子形成对比，后者在脊椎动物进化的巨大时间尺度上似乎没有变化。脊椎动物附肢发育的转录控制在鱼类的共同祖先中可能已经非常复杂，这意味着调控网络的细微变化更有可能是表型变化的原因，而不是整个调控结构域的从头增加。最后，我们讨论了在测试增强子功能时依赖物种间转基因的危险，并呼吁在推断增强子元件的进化史时进行更受控的调控交换实验。
Differential gene expression is the core of development, mediating the genetic changes necessary for determining cell identity. The regulation of gene activity by cis-acting elements (e.g., enhancers) is a crucial mechanism for determining differential gene activity by precise control of gene expression in embryonic space and time. Modifications to regulatory regions can have profound impacts on phenotype, and therefore developmental and evolutionary biologists have increasingly focused on elucidating the transcriptional control of genes that build and pattern body plans. Here, we trace the evolutionary history of transcriptional control of three loci key to vertebrate appendage development (Fgf8, Shh, and HoxD/A). Within and across these regulatory modules, we find both complex and flexible regulation in contrast with more fixed enhancers that appear unchanged over vast timescales of vertebrate evolution. The transcriptional control of vertebrate appendage development was likely already incredibly complex in the common ancestor of fish, implying that subtle changes to regulatory networks were more likely responsible for alterations in phenotype rather than the de novo addition of whole regulatory domains. Finally, we discuss the dangers of relying on inter-species transgenesis when testing enhancer function, and call for more controlled regulatory swap experiments when inferring the evolutionary history of enhancer elements.