Structural phylogenomics retrodicts the origin of the genetic code and uncovers the evolutionary impact of protein flexibility.

Structural phylogenomics retrodicts the origin of the genetic code and uncovers the evolutionary impact of protein flexibility.
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DOI:
10.1371/journal.pone.0072225
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Caetano-Anollés D
Caetano-Anollés D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Caetano-Anollés G;Wang M;Caetano-Anollés D

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遗传密码塑造了遗传库。它的起源半个多世纪以来一直困扰着分子科学家,仍然是一个长期存在的谜。在这里,我们表明遗传密码的起源与氨酰-tRNA合成酶的历史及其与tRNA的相互作用密切相关。从数百个基因组的结构普查中得出的蛋白质结构域家族进化出现的时间线揭示了“可操作的”RNA密码的早期出现和标准遗传密码的晚期实施。密码子特异性的出现和氨基酸电荷的出现涉及氨基酰-tRNA合成酶和tRNA结构的紧密协同进化以及结构募集。值得注意的是,在标准编码之前出现的单域蛋白的氨基酸和二肽组成表明,具有与酪氨酰-tRNA和丝氨酰-tRNA合成酶催化结构域同源结构的古老合成酶能够形成肽键和氨基酰化。结果表明,遗传是通过多肽和核酸辅助因子之间的共同进化相互作用而产生的,这是一种有利于出现的蛋白质的柔韧性和折叠的提取机制。随着现代蛋白质结构的早期兴起,这些表型稳健性的增强很可能内化到新兴的遗传系统中。
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.
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