29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome.
29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome.
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DOI：
10.1371/journal.pone.0043128
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Haussler D
中科院分区：
文献类型：
--
作者：
Lowe CB;Haussler D
最近的研究支持这样一种观点，即基因调控的变化，而不是基因本身的变化，在形态进化中起着重要作用。基因调控在很大程度上依赖于转录因子结合位点。研究人员现在能够使用现有的29个哺乳动物基因组来测量结合位点水平的选择性约束。这个详细的限制图表明，哺乳动物基因组在很大程度上选择了移动的元件片段作为基因调控序列。在人类基因组中，我们检测到超过280，000个推定的调控元件，总计约7 Mb的序列，其起源于移动的元件插入。这些推定的调控区域是保守的非外显子元件（CNEE），其在人类中显示出相当大的跨物种约束和持续负选择的特征，但不出现在已知的成熟转录物中。这些推定的调控元件来自SINE、LINE、LTR和DNA转座子插入。我们证明，至少有11%，估计20%，在人类基因组中的基因调控序列显示跨物种的保护是增选从移动的元素。从移动的元件中增选的CNEE在基因组中的位置与一般CNEE的位置非常相似，除了在最大的基因沙漠中心，可识别的增选事件相对罕见。我们发现，某些区域的移动的元素插入更有可能举行纯化选择比其他人。特别是，我们展示了6个例子，其中旁系同源的情况下，经常增选的移动的元件区域定义的序列基序，密切匹配的转录因子的结合概况。
Recent research supports the view that changes in gene regulation, as opposed to changes in the genes themselves, play a significant role in morphological evolution. Gene regulation is largely dependent on transcription factor binding sites. Researchers are now able to use the available 29 mammalian genomes to measure selective constraint at the level of binding sites. This detailed map of constraint suggests that mammalian genomes co-opt fragments of mobile elements to act as gene regulatory sequence on a large scale. In the human genome we detect over 280,000 putative regulatory elements, totaling approximately 7 Mb of sequence, that originated as mobile element insertions. These putative regulatory regions are conserved non-exonic elements (CNEEs), which show considerable cross-species constraint and signatures of continued negative selection in humans, yet do not appear in a known mature transcript. These putative regulatory elements were co-opted from SINE, LINE, LTR and DNA transposon insertions. We demonstrate that at least 11%, and an estimated 20%, of gene regulatory sequence in the human genome showing cross-species conservation was co-opted from mobile elements. The location in the genome of CNEEs co-opted from mobile elements closely resembles that of CNEEs in general, except in the centers of the largest gene deserts where recognizable co-option events are relatively rare. We find that regions of certain mobile element insertions are more likely to be held under purifying selection than others. In particular, we show 6 examples where paralogous instances of an often co-opted mobile element region define a sequence motif that closely matches a transcription factor’s binding profile.
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