Faculty of Medicine, Laboratory AGEIS EA 7407, Team Tools for e-Gnosis Medical & Labcom CNRS/UGA/OrangeLabs Telecoms4Health, Université Grenoble Alpes, F-38700, La Tronche, France.
The National Natural History Collections, The Hebrew University of Jerusalem, 91404, Jerusalem, Israel.
BMC Genet. 2020 Jan 23;21(1):7. doi: 10.1186/s12863-020-0812-2.
Theoretical minimal RNA rings code by design over the shortest length once for each of the 20 amino acids, a start and a stop codon, and form stem-loop hairpins. This defines at most 25 RNA rings of 22 nucleotides. As a group, RNA rings mimick numerous prebiotic and early life biomolecular properties: tRNAs, deamination gradients and replication origins, emergence of codon preferences for the natural circular code, and contents of early protein coding genes. These properties result from the RNA ring's in silico design, based mainly on coding nonredundancy among overlapping translation frames, as the genetic code's codon-amino acid assignments determine. RNA rings resemble ancestral tRNAs, defining RNA ring anticodons and corresponding cognate amino acids. Surprisingly, all examined RNA ring properties coevolve with genetic code integration ranks of RNA ring cognates, as if RNA rings mimick prebiotic and early life evolution.
Distances between RNA rings were calculated using different evolutionary models. Associations between these distances and genetic code evolutionary hypotheses detect evolutionary models best describing RNA ring diversification.
Here pseudo-phylogenetic analyses of RNA rings produce clusters corresponding to the primordial code in tRNA acceptor stems, more so when substitution matrices from neutrally evolving pseudogenes are used rather than from functional protein coding genes reflecting selection for conserving amino acid properties.
Results indicate RNA rings with recent cognates evolved from those with early cognates. Hence RNA rings, as designed by the genetic code's structure, simulate tRNA stem evolution and prebiotic history along neutral chemistry-driven mutation regimes.
理论上最小 RNA 环通过设计在最短长度上为每个 20 种氨基酸、一个起始和一个终止密码子编码一次,并形成茎环发夹。这最多定义了 22 个核苷酸的 25 个 RNA 环。作为一个整体,RNA 环模拟了许多前生物和早期生命生物分子特性:tRNA、脱氨酶梯度和复制起点、自然圆形密码子偏好密码子的出现,以及早期蛋白质编码基因的内容。这些特性源自 RNA 环的计算机设计,主要基于重叠翻译框架之间的编码非冗余性,因为遗传密码的密码子-氨基酸分配决定了这一点。RNA 环类似于古老的 tRNA,定义了 RNA 环反密码子和相应的同源氨基酸。令人惊讶的是,所有检查的 RNA 环特性都与 RNA 环同源物的遗传密码整合等级共同进化,就好像 RNA 环模拟了前生物和早期生命的进化。
使用不同的进化模型计算 RNA 环之间的距离。这些距离与遗传密码进化假设之间的关联检测出最能描述 RNA 环多样化的进化模型。
这里对 RNA 环进行了伪系统发育分析,产生了与 tRNA 接受茎中原始密码子相对应的聚类,当使用来自中性进化假基因的取代矩阵而不是来自反映保守氨基酸特性选择的功能蛋白编码基因的取代矩阵时,情况更是如此。
结果表明,具有最近同源物的 RNA 环是从具有早期同源物的 RNA 环进化而来的。因此,RNA 环按照遗传密码结构设计,模拟了 tRNA 茎的进化和中性化学驱动的突变机制下的前生物历史。