Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois, Urbana, Illinois, United States of America.
PLoS One. 2013 Aug 21;8(8):e72225. doi: 10.1371/journal.pone.0072225. eCollection 2013.
The genetic code shapes the genetic repository. Its origin has puzzled molecular scientists for over half a century and remains a long-standing mystery. Here we show that the origin of the genetic code is tightly coupled to the history of aminoacyl-tRNA synthetase enzymes and their interactions with tRNA. A timeline of evolutionary appearance of protein domain families derived from a structural census in hundreds of genomes reveals the early emergence of the 'operational' RNA code and the late implementation of the standard genetic code. The emergence of codon specificities and amino acid charging involved tight coevolution of aminoacyl-tRNA synthetases and tRNA structures as well as episodes of structural recruitment. Remarkably, amino acid and dipeptide compositions of single-domain proteins appearing before the standard code suggest archaic synthetases with structures homologous to catalytic domains of tyrosyl-tRNA and seryl-tRNA synthetases were capable of peptide bond formation and aminoacylation. Results reveal that genetics arose through coevolutionary interactions between polypeptides and nucleic acid cofactors as an exacting mechanism that favored flexibility and folding of the emergent proteins. These enhancements of phenotypic robustness were likely internalized into the emerging genetic system with the early rise of modern protein structure.
遗传密码塑造了遗传库。其起源令分子生物学家困惑了半个多世纪，至今仍是一个长期存在的谜团。在这里，我们表明遗传密码的起源与氨酰-tRNA 合成酶及其与 tRNA 的相互作用的历史紧密相关。从数百个基因组的结构普查中得出的蛋白质结构域家族的进化出现时间轴表明，“操作”RNA 密码的早期出现和标准遗传密码的后期实施。密码子特异性和氨基酸加载的出现涉及氨酰-tRNA 合成酶和 tRNA 结构的紧密共进化以及结构募集的事件。值得注意的是，在标准密码出现之前出现的具有单结构域蛋白质的氨基酸和二肽组成表明，与酪氨酸-tRNA 和丝氨酸-tRNA 合成酶的催化结构域具有同源性的古老合成酶能够进行肽键形成和氨酰化。结果表明，遗传学是通过多肽和核酸辅因子之间的协同进化相互作用而产生的，这是一种精确的机制，有利于新出现的蛋白质的灵活性和折叠。随着现代蛋白质结构的早期出现，这些表型稳健性的增强很可能被内化到新兴的遗传系统中。
