Department of MCD Biology and Chemistry/Biochemistry, University of Colorado, Boulder, CO 80309-0347, USA.
J Mol Evol. 2009 Nov;69(5):406-29. doi: 10.1007/s00239-009-9270-1. Epub 2009 Oct 1.
By combining crystallographic and NMR structural data for RNA-bound amino acids within riboswitches, aptamers, and RNPs, chemical principles governing specific RNA interaction with amino acids can be deduced. Such principles, which we summarize in a "polar profile", are useful in explaining newly selected specific RNA binding sites for free amino acids bearing varied side chains charged, neutral polar, aliphatic, and aromatic. Such amino acid sites can be queried for parallels to the genetic code. Using recent sequences for 337 independent binding sites directed to 8 amino acids and containing 18,551 nucleotides in all, we show a highly robust connection between amino acids and cognate coding triplets within their RNA binding sites. The apparent probability (P) that cognate triplets around these sites are unrelated to binding sites is congruent with 5.3 x 10(-45) for codons overall, and P congruent with 2.1 x 10(-46) for cognate anticodons. Therefore, some triplets are unequivocally localized near their present amino acids. Accordingly, there was likely a stereochemical era during evolution of the genetic code, relying on chemical interactions between amino acids and the tertiary structures of RNA binding sites. Use of cognate coding triplets in RNA binding sites is nevertheless sparse, with only 21% of possible triplets appearing. Reasoning from such broad recurrent trends in our results, a majority (approximately 75%) of modern amino acids entered the code in this stereochemical era; nevertheless, a minority (approximately 21%) of modern codons and anticodons were assigned via RNA binding sites. A Direct RNA Template scheme embodying a credible early history for coded peptide synthesis is readily constructed based on these observations.
通过将 RNA 结合开关、适体和 RNP 中结合的氨基酸的晶体学和 NMR 结构数据相结合，可以推导出控制特定 RNA 与氨基酸相互作用的化学原理。我们将这些原理总结为“极性分布”，这对于解释新选择的具有不同侧链（带电、中性极性、脂肪族和芳香族）的游离氨基酸的特定 RNA 结合位点非常有用。可以查询这些氨基酸位点以找到与遗传密码的相似之处。使用最近的 337 个独立结合位点序列，这些序列针对 8 种氨基酸，总共包含 18551 个核苷酸，我们在这些 RNA 结合位点内的氨基酸与其同源编码三联体之间显示出高度稳健的联系。这些位点周围的同源三联体与结合位点无关的明显概率 (P) 与密码子的总体概率 5.3 x 10(-45) 一致，而与同源反密码子的概率 P 一致 2.1 x 10(-46)。因此，有些三联体明确位于其氨基酸附近。因此，在遗传密码的进化过程中，可能存在一个依赖于氨基酸与 RNA 结合位点的三级结构之间的化学相互作用的立体化学时代。尽管如此，在 RNA 结合位点中使用同源编码三联体仍然很少，只有 21%的可能三联体出现。从我们结果中的这些广泛的反复出现的趋势推断，大多数（约 75%）现代氨基酸是在这个立体化学时代进入密码子的；然而，只有少数（约 21%）现代密码子和反密码子是通过 RNA 结合位点分配的。根据这些观察结果，很容易构建一个体现编码肽合成可信早期历史的直接 RNA 模板方案。
