Schmidt Markus
Biofaction, Vienna, Austria.
Biosystems. 2019 Nov;185:104015. doi: 10.1016/j.biosystems.2019.104015. Epub 2019 Aug 10.
Analysing or engineering the genetic code has mainly been considered as an approach to reduce or increase the mutational robustness of the genetic code, i.e. the error tolerance in DNA mutations, or to enable the incorporation of non-canonical amino acids. The approach of "semantic containment", however, is less interested in altering the mutational tolerance of the standard code, but to create synthetic alternative genetic codes that limit or all together impede horizontal gene transfer between a natural and genomically recoded organisms (GRO). A major claim or conjecture of semantic containment is: "the farther, the safer", meaning, the less similarity there is between two codes, the less chance of a horizontal gene transfer, and the stronger the genetic firewall. So far, no metrics were available to measure and quantify the "genetic distance" between different genetic codes. Such a metric, however, is iis paramount to allow the experimental testing and evaluation of the validity of semantic biocontainment for the first time. Here, we introduce a metric space to measure exactly the distance (dissimilarity) between different genetic codes, in order to provide a framework to evaluate the relation between distance and strength of a genetic firewall. Results are presented that incorporate bespoken metrics when producing alternative genetic codes according to predefined goals, specifications and limitations. Finally, as an outlook, implications and challenges for genetic firewall(s) are discussed for dual- and multi-code systems.
分析或设计遗传密码主要被视为一种降低或提高遗传密码突变稳健性（即DNA突变中的容错能力）的方法，或者是用于实现非标准氨基酸的掺入。然而，“语义封闭”方法对改变标准密码的突变耐受性兴趣不大，而是致力于创建合成的替代遗传密码，以限制或完全阻止天然生物与基因组重编码生物（GRO）之间的水平基因转移。语义封闭的一个主要主张或推测是：“距离越远，越安全”，意思是，两种密码之间的相似性越低，水平基因转移的可能性就越小，遗传防火墙就越强。到目前为止，还没有可用于测量和量化不同遗传密码之间“遗传距离”的指标。然而，这样一个指标对于首次允许对语义生物封闭的有效性进行实验测试和评估至关重要。在此，我们引入一个度量空间来精确测量不同遗传密码之间的距离（差异），以便提供一个框架来评估遗传距离与遗传防火墙强度之间的关系。给出了在根据预定义的目标、规格和限制生成替代遗传密码时纳入定制指标的结果。最后，作为展望，讨论了双密码和多密码系统中遗传防火墙的影响和挑战。
