Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada; Department of Chemistry, The University of Western Ontario, London, ON N6A 5B7, Canada.
Biochim Biophys Acta Gen Subj. 2017 Nov;1861(11 Pt B):3070-3080. doi: 10.1016/j.bbagen.2017.01.031. Epub 2017 Jan 30.
The conservation of the genetic code indicates that there was a single origin, but like all genetic material, the cell's interpretation of the code is subject to evolutionary pressure. Single nucleotide variations in tRNA sequences can modulate codon assignments by altering codon-anticodon pairing or tRNA charging. Either can increase translation errors and even change the code. The frozen accident hypothesis argued that changes to the code would destabilize the proteome and reduce fitness. In studies of model organisms, mistranslation often acts as an adaptive response. These studies reveal evolutionary conserved mechanisms to maintain proteostasis even during high rates of mistranslation.
This review discusses the evolutionary basis of altered genetic codes, how mistranslation is identified, and how deviations to the genetic code are exploited. We revisit early discoveries of genetic code deviations and provide examples of adaptive mistranslation events in nature. Lastly, we highlight innovations in synthetic biology to expand the genetic code.
The genetic code is still evolving. Mistranslation increases proteomic diversity that enables cells to survive stress conditions or suppress a deleterious allele. Genetic code variants have been identified by genome and metagenome sequence analyses, suppressor genetics, and biochemical characterization.
Understanding the mechanisms of translation and genetic code deviations enables the design of new codes to produce novel proteins. Engineering the translation machinery and expanding the genetic code to incorporate non-canonical amino acids are valuable tools in synthetic biology that are impacting biomedical research. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.
遗传密码的保守性表明它只有一个单一的起源，但和所有遗传物质一样，细胞对密码子的解读也受到进化压力的影响。tRNA 序列中的单个核苷酸变异可以通过改变密码子-反密码子配对或 tRNA 充电来调节密码子的分配。这两种方式都可以增加翻译错误，甚至改变密码子。“冻结事故假说”认为，密码子的改变会使蛋白质组不稳定，降低适应性。在模式生物的研究中，错译通常是一种适应性反应。这些研究揭示了即使在高错译率下，仍有保守机制来维持蛋白质组的稳态。
本文讨论了改变遗传密码的进化基础，错译是如何被识别的，以及如何利用遗传密码的偏差。我们重新审视了遗传密码偏差的早期发现，并提供了自然界中适应性错译事件的例子。最后，我们强调了合成生物学中的创新，以扩展遗传密码。
遗传密码仍在进化。错译增加了蛋白质组的多样性，使细胞能够在应激条件下存活或抑制有害等位基因。遗传密码变体已通过基因组和宏基因组序列分析、抑制遗传和生化特征来鉴定。
理解翻译和遗传密码偏差的机制，使设计产生新蛋白质的新密码子成为可能。工程化翻译机制和扩展遗传密码以纳入非规范氨基酸是合成生物学中的有价值工具，正在影响着生物医学研究。本文是题为“合成生物学的生物化学-最新进展”的特刊的一部分，客座编辑：Ilka Heinemann 博士和 Patrick O'Donoghue 博士。
