Shultzaberger R K, Bucheimer R E, Rudd K E, Schneider T D
University of Maryland, College Park, 20742, USA.
J Mol Biol. 2001 Oct 12;313(1):215-28. doi: 10.1006/jmbi.2001.5040.
During translational initiation in prokaryotes, the 3' end of the 16S rRNA binds to a region just upstream of the initiation codon. The relationship between this Shine-Dalgarno (SD) region and the binding of ribosomes to translation start-points has been well studied, but a unified mathematical connection between the SD, the initiation codon and the spacing between them has been lacking. Using information theory, we constructed a model that treats these three components uniformly by assigning to the SD and the initiation region (IR) conservations in bits of information, and by assigning to the spacing an uncertainty, also in bits. To build the model, we first aligned the SD region by maximizing the information content there. The ease of this process confirmed the existence of the SD pattern within a set of 4122 reviewed and revised Escherichia coli gene starts. This large data set allowed us to show graphically, by sequence logos, that the spacing between the SD and the initiation region affects both the SD site conservation and its pattern. We used the aligned SD, the spacing, and the initiation region to model ribosome binding and to identify gene starts that do not conform to the ribosome binding site model. A total of 569 experimentally proven starts are more conserved (have higher information content) than the full set of revised starts, which probably reflects an experimental bias against the detection of gene products that have inefficient ribosome binding sites. Models were refined cyclically by removing non-conforming weak sites. After this procedure, models derived from either the original or the revised gene start annotation were similar. Therefore, this information theory-based technique provides a method for easily constructing biologically sensible ribosome binding site models. Such models should be useful for refining gene-start predictions of any sequenced bacterial genome.
在原核生物的翻译起始过程中，16S rRNA的3'端与起始密码子上游的一个区域结合。这种Shine-Dalgarno（SD）区域与核糖体与翻译起始点的结合之间的关系已经得到了充分研究，但SD、起始密码子及其之间的间隔之间缺乏统一的数学联系。利用信息论，我们构建了一个模型，通过为SD和起始区域（IR）分配信息比特的保守性，并为间隔分配同样以比特为单位的不确定性，来统一处理这三个组件。为了构建模型，我们首先通过最大化SD区域的信息含量来对其进行比对。这一过程的简便性证实了在一组4122个经过审查和修订的大肠杆菌基因起始序列中存在SD模式。这个大数据集使我们能够通过序列标识以图形方式显示SD与起始区域之间的间隔会影响SD位点的保守性及其模式。我们利用比对后的SD、间隔和起始区域来模拟核糖体结合，并识别不符合核糖体结合位点模型的基因起始序列。共有569个经过实验验证的起始序列比全套修订后的起始序列更保守（具有更高的信息含量），这可能反映了实验中对核糖体结合位点效率低下的基因产物检测的偏差。通过去除不符合要求的弱位点，模型得以循环优化。经过这一过程后，从原始或修订后的基因起始注释中得出的模型相似。因此，这种基于信息论的技术提供了一种轻松构建生物学上合理的核糖体结合位点模型的方法。这样的模型对于完善任何已测序细菌基因组的基因起始预测应该是有用的。
