Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Bioinformatics. 2012 Sep 15;28(18):i395-i401. doi: 10.1093/bioinformatics/bts400.
Genomic context analysis, also known as phylogenetic profiling, is widely used to infer functional interactions between proteins but rarely applied to non-coding cis-regulatory DNA elements. We were wondering whether this approach could provide insights about utlraconserved non-coding elements (UCNEs). These elements are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes. Their molecular functions and the reasons for their high degree of conservation remain enigmatic.
In a special setting of genomic context analysis, we analyzed the fate of GRBs after a whole-genome duplication event in five fish genomes. We found that in most cases all UCNEs were retained together as a single block, whereas the corresponding target genes were often retained in two copies, one completely devoid of UCNEs. This 'winner-takes-all' pattern suggests that UCNEs of a GRB function in a highly cooperative manner. We propose that the multitude of interactions between UCNEs is the reason for their extreme sequence conservation.
Supplementary data are available at Bioinformatics online and at http://ccg.vital-it.ch/ucne/
基因组背景分析,也称为系统发育分析,被广泛用于推断蛋白质之间的功能相互作用,但很少应用于非编码顺式调控 DNA 元件。我们想知道这种方法是否可以提供关于超保守非编码元件(UCNEs)的见解。这些元件组织成大的簇,称为关键发育基因周围的基因调控块(GRB)。它们的分子功能及其高度保守的原因仍然是个谜。
在基因组背景分析的一个特殊设置中,我们分析了五个鱼类基因组中全基因组复制事件后 GRB 的命运。我们发现,在大多数情况下,所有的 UCNEs 都作为一个单独的块保留在一起,而相应的靶基因通常保留为两个副本,一个完全没有 UCNEs。这种“赢家通吃”的模式表明,GRB 的 UCNEs 以高度协作的方式发挥作用。我们提出,UCNEs 之间的多种相互作用是其极端序列保守的原因。
补充数据可在 Bioinformatics 在线和 http://ccg.vital-it.ch/ucne/ 上获得。