Abstract

The universal genetic code, which is the foundation of cellular organization for almost all organisms, has fostered the exchange of genetic information from very different paths of evolution. The result of this communication network of potentially beneficial traits can be observed as modern biodiversity. Today, the genetic modification techniques of synthetic biology allow for the design of specialized organisms and their employment as tools, creating an artificial biodiversity based on the same universal genetic code. As there is no natural barrier towards the proliferation of genetic information which confers an advantage for a certain species, the naturally evolved genetic pool could be irreversibly altered if modified genetic information is exchanged. We argue that an alien genetic code which is incompatible with nature is likely to assure the inhibition of all mechanisms of genetic information transfer in an open environment. The two conceivable routes to synthetic life are either de novo cellular design or the successive alienation of a complex biological organism through laboratory evolution. Here, we present the strategies that have been utilized to fundamentally alter the genetic code in its decoding rules or its molecular representation and anticipate future avenues in the pursuit of robust biocontainment.

Highlights

  • The design and manufacturing of specialized biological systems promises to be the giant leap in human technology to advance many aspects of our society in unimaginable ways

  • Genes 2019, 10, 17 between organisms can be distinguished from the emerging field of xenobiology (XB), which aims to expand the framework of natural chemistries within living cells through the incorporation of non-natural building blocks [16,17]

  • The genome-wide substitution of the UAG codon with a synonymous codon allows for the deletion of the competing release factor (RF1), which mitigates the detrimental effects of the code ambiguity and enhances the non-canonical amino acids (ncAAs) incorporation efficiency [43]

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Summary

Introduction

The design and manufacturing of specialized biological systems promises to be the giant leap in human technology to advance many aspects of our society in unimaginable ways. Life on Earth is a reservoir of complex organized systems, displaying different levels of control over their respective dynamic environments and intricate physiological processes to achieve robust autonomy [18,19] In this context, the genetic information encoding the organization of an organism can persist in two ways, either within a species through reproduction (vertical gene transfer, VGT), or between species through horizontal gene transfer (HGT). Exchanging information between species at the genetic level is only possible for individuals maintaining the same physicochemical character (DNA and RNA) and decoding logic (transcription and translation) in their genetic code, making the genetic code the lingua franca of life on Earth [17] It is the universality of the genetic code which makes GMOs designed to be employed in open environments a potential threat, as leakage of synthetic genetic information polymers might contaminate the naturally evolved genetic pool and alter entire ecosystems [4]. (bottom-up) [30,31] or the successive alienation of a complex natural organism through laboratory evolution (top-down) [32,33]

Basic Considerations for an Alien Central Dogma
Altering the Meaning of the Genetic Code
Stop Codon Reassignment
Sense Codon Reassignment
Minimal Cell Design
Altering the Identity of the Genetic Code
Frameshift Codons
Synthetic Base Pairs
Alternative DNA Backbone Motifs
The Farther the Safer
Alienation Far beyond the Canonical Chemistries of Life
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