The Coevolution of Genes and the Genetic Code

The Standard Genetic Code (SGC) is the mapping of nucleic acids into polypeptides that is employed, sometimes with minor variations1, in every organism, organelle and virus. The organization of the SGC is highly non-random2-8. In the four decades since the discovery of the SGC a large spectrum of hypotheses have been conceived to explain how its organization came about. These include a variety of load minimizing hypotheses2,3,5,6,9-15, the frozen accident hypothesis16, the ambiguity reduction hypothesis17,18, the stereochemical hypothesis14,16,19-25, and the metabolic coevolutionary hypothesis26,27. None of these hypotheses has laid down a theory that is fully fledged in the sense that it (i) begins from biological or biochemical considerations, (ii) derives the evolutionary mechanisms that follow from such considerations, and (iii) shows how these mechanisms can reproduce the patterns in the organization of the SGC. Here we present the first fully fledged theory for the evolution of the SGC. The theory derives from two fundamental observations: first, there are patterns in the SGC that strongly suggest that systematic error in replication and translation played a causal role in its evolution2-8; and second, the evolution of a genetic code is mediated through the protein-coding genes, where selection acts upon the proteins which are the product of translating these genes with the genetic code16. We derive the evolutionary mechanisms of code formation that follow from these observations, and show how these mechanisms reproduce two of the salient organizational patterns of the SGC. (Superscript numbers in text denote references cited at the end of the paper.)