Distinct Functional Constraints Partition Sequence Conservation in a cis-Regulatory Element
Distinct Functional Constraints Partition Sequence Conservation in a cis-Regulatory Element
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DOI：
10.1371/journal.pgen.1002095
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发表时间：
2011-06-01
期刊：
影响因子：
4.5
通讯作者：
Ruvinsky, Ilya
中科院分区：
文献类型：
--
作者：
Barriere, Antoine;Gordon, Kacy L.;Ruvinsky, Ilya
不同的功能限制导致基因组之间不同的进化速率。为了理解为什么某些序列比其他人在一个单一的顺式调控基因座进化得更快，我们研究了秀丽隐杆线虫UNC-47基因启动子的功能和进化动力学。我们发现该启动子由两个不同的结构域组成。近端启动子是保守的，并且在很大程度上足以指导适当的空间表达。远端启动子在几种密切相关的线虫之间显示出很少的保守性。尽管存在这种差异，但来自所有物种的序列都赋予了表达的稳健性，认为这种功能不需要大量的序列保守性。我们发现，即使是不相关的序列也有能力促进稳健的表达。所有这些稳健性促进序列共有的一个突出特征是与核小体消耗一致的AT富集的核苷酸组合物。由于一般序列组成，可以保持尽管序列营业额，我们的研究结果解释了不同的功能限制如何可能导致截然不同的启动子内的序列分歧率。
Different functional constraints contribute to different evolutionary rates across genomes. To understand why some sequences evolve faster than others in a single cis-regulatory locus, we investigated function and evolutionary dynamics of the promoter of the Caenorhabditis elegans unc-47 gene. We found that this promoter consists of two distinct domains. The proximal promoter is conserved and is largely sufficient to direct appropriate spatial expression. The distal promoter displays little if any conservation between several closely related nematodes. Despite this divergence, sequences from all species confer robustness of expression, arguing that this function does not require substantial sequence conservation. We showed that even unrelated sequences have the ability to promote robust expression. A prominent feature shared by all of these robustness-promoting sequences is an AT-enriched nucleotide composition consistent with nucleosome depletion. Because general sequence composition can be maintained despite sequence turnover, our results explain how different functional constraints can lead to vastly disparate rates of sequence divergence within a promoter.