Root-Bernstein Robert, Root-Bernstein Meredith
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Department of Bioscience, Aarhus University, Aarhus, Denmark.
J Theor Biol. 2016 May 21;397:115-27. doi: 10.1016/j.jtbi.2016.02.030. Epub 2016 Mar 4.
We have proposed that the ribosome may represent a missing link between prebiotic chemistries and the first cells. One of the predictions that follows from this hypothesis, which we test here, is that ribosomal RNA (rRNA) must have encoded the proteins necessary for ribosomal function. In other words, the rRNA also functioned pre-biotically as mRNA. Since these ribosome-binding proteins (rb-proteins) must bind to the rRNA, but the rRNA also functioned as mRNA, it follows that rb-proteins should bind to their own mRNA as well. This hypothesis can be contrasted to a "null" hypothesis in which rb-proteins evolved independently of the rRNA sequences and therefore there should be no necessary similarity between the rRNA to which rb-proteins bind and the mRNA that encodes the rb-protein. Five types of evidence reported here support the plausibility of the hypothesis that the mRNA encoding rb-proteins evolved from rRNA: (1) the ubiquity of rb-protein binding to their own mRNAs and autogenous control of their own translation; (2) the higher-than-expected incidence of Arginine-rich modules associated with RNA binding that occurs in rRNA-encoded proteins; (3) the fact that rRNA-binding regions of rb-proteins are homologous to their mRNA binding regions; (4) the higher than expected incidence of rb-protein sequences encoded in rRNA that are of a high degree of homology to their mRNA as compared with a random selection of other proteins; and (5) rRNA in modern prokaryotes and eukaryotes encodes functional proteins. None of these results can be explained by the null hypothesis that assumes independent evolution of rRNA and the mRNAs encoding ribosomal proteins. Also noteworthy is that very few proteins bind their own mRNAs that are not associated with ribosome function. Further tests of the hypothesis are suggested: (1) experimental testing of whether rRNA-encoded proteins bind to rRNA at their coding sites; (2) whether tRNA synthetases, which are also known to bind to their own mRNAs, are encoded by the tRNA sequences themselves; (3) and the prediction that archaeal and prokaryotic (DNA-based) genomes were built around rRNA "genes" so that rRNA-related sequences will be found to make up an unexpectedly high proportion of these genomes.
我们提出核糖体可能代表了益生元化学与首批细胞之间缺失的环节。基于这一假说(我们在此对其进行验证)得出的一个预测是,核糖体RNA(rRNA)必定编码了核糖体功能所需的蛋白质。换句话说,rRNA在生命起源之前也起到了信使核糖核酸(mRNA)的作用。由于这些核糖体结合蛋白(rb蛋白)必须与rRNA结合,但rRNA同时也起到mRNA的作用,因此可以推断rb蛋白也应该与其自身的mRNA结合。这一假说可以与“零假设”形成对比,在“零假设”中,rb蛋白独立于rRNA序列进化,因此rb蛋白所结合的rRNA与编码rb蛋白的mRNA之间不应存在必然的相似性。本文报道的五类证据支持了编码rb蛋白的mRNA由rRNA进化而来这一假说的合理性:(1)rb蛋白与其自身mRNA结合以及对自身翻译进行自体调控的普遍性;(2)在rRNA编码的蛋白质中,与RNA结合相关的富含精氨酸模块的出现频率高于预期;(3)rb蛋白的rRNA结合区域与其mRNA结合区域同源这一事实;(4)与随机选择的其他蛋白质相比,rRNA中编码的rb蛋白序列与其mRNA具有高度同源性的出现频率高于预期;(5)现代原核生物和真核生物中的rRNA编码功能性蛋白质。“零假设”假定rRNA与编码核糖体蛋白的mRNA独立进化,上述任何结果均无法用该假设来解释。同样值得注意的是,很少有与核糖体功能无关的蛋白质会与其自身的mRNA结合。文中还提出了对该假说的进一步验证:(1)对rRNA编码的蛋白质是否在其编码位点与rRNA结合进行实验验证;(2)同样已知会与其自身mRNA结合的tRNA合成酶是否由tRNA序列本身编码;(3)以及古菌和原核生物(基于DNA)的基因组围绕rRNA“基因”构建,从而会发现与rRNA相关的序列在这些基因组中所占比例意外之高这一预测。