How To Quantify a Genetic Firewall? A Polarity‐Based Metric for Genetic Code Engineering

Genetic code engineering aims to produce organisms that translate genetic information in a different way from that prescribed by the standard genetic code. This endeavor could eventually lead to genetic isolation, where an organism that operates under a different genetic code will not be able to transfer functional genes with other living species, thereby standing behind a genetic firewall. It is not clear however, how distinct the code should be, or how to measure the distance. We have developed a metric (Δ(code)) where we assigned polarity indices (clog D (7)) to amino acids to calculate the distances between pairs of genetic codes. We then calculated the distance between a set of 204 genetic codes, including the 24 known distinct natural codes, 11 extreme‐distance codes created computationally, nine theoretical special purpose codes from literature and 160 codes in which canonical amino acids were replaced by noncanonical chemical analogues. The metric can be used for building strategies towards creating semantically alienated organisms, and testing the strength of genetic firewalls. This metric provides the basis for a map of the genetic codes that could guide future efforts towards novel biochemical worlds, biosafety and deep barcoding applications.