Exonic remnants of whole-genome duplication reveal cis-regulatory function of coding exons.
Exonic remnants of whole-genome duplication reveal cis-regulatory function of coding exons.
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DOI：
10.1093/nar/gkp1124
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发表时间：
2010-03
影响因子：
14.9
通讯作者：
Lenhard B
中科院分区：
文献类型：
--
作者：
Dong X;Navratilova P;Fredman D;Drivenes Ø;Becker TS;Lenhard B
使用比较基因组学的方法来重建基因组调控块（GRBs）的命运，并确定外显子残留物，幸存下来的消失后，他们的宿主基因全基因组复制（WGD）在硬骨鱼，我们发现了一组38个候选顺式调控编码外显子（RCEs）与预测的靶基因。这些元件表明，在硬骨鱼WGD后重叠的蛋白质编码和调控信息的进化分离。我们提出的证据表明，相应的哺乳动物外显子仍然在编码和非编码选择压力下，比宿主基因和几个控制组中的其他蛋白质编码外显子更保守，并与相同区域中高度保守的非编码元件共享关键特征。现有的实验数据证实了它们的双重功能。此外，我们还展示了源自脊椎动物2R WGD的人类外显子残留物的实例。我们的研究结果表明，长距离的顺式调控输入发育基因不仅限于非编码区，但也可以重叠无关基因的编码序列。因此，GRB中的外显子调控元件可能在功能上等同于非编码区中的调控元件，这需要重新评估序列空间，以寻找长程调控元件并通过实验测试其活性。
Using a comparative genomics approach to reconstruct the fate of genomic regulatory blocks (GRBs) and identify exonic remnants that have survived the disappearance of their host genes after whole-genome duplication (WGD) in teleosts, we discover a set of 38 candidate cis-regulatory coding exons (RCEs) with predicted target genes. These elements demonstrate evolutionary separation of overlapping protein-coding and regulatory information after WGD in teleosts. We present evidence that the corresponding mammalian exons are still under both coding and non-coding selection pressure, are more conserved than other protein coding exons in the host gene and several control sets, and share key characteristics with highly conserved non-coding elements in the same regions. Their dual function is corroborated by existing experimental data. Additionally, we show examples of human exon remnants stemming from the vertebrate 2R WGD. Our findings suggest that long-range cis-regulatory inputs for developmental genes are not limited to non-coding regions, but can also overlap the coding sequence of unrelated genes. Thus, exonic regulatory elements in GRBs might be functionally equivalent to those in non-coding regions, calling for a re-evaluation of the sequence space in which to look for long-range regulatory elements and experimentally test their activity.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
影响因子：
4.4
作者：
Chen, Hsuan Pu;Lin, Andy;Smith, Desmond J.
通讯作者：
Smith, Desmond J.
影响因子：
7
作者：
Kikuta, Hiroshi;Laplante, Mary;Becker, Thomas S.
通讯作者：
Becker, Thomas S.
影响因子：
7
作者：
Hardison, RC;Roskin, KM;Haussler, D
通讯作者：
Haussler, D