Abstract
Nearly 50 years ago, Francis Crick propounded the frozen accident scenario for the evolution of the genetic code along with the hypothesis that the early translation system consisted primarily of RNA. Under the frozen accident perspective, the code is universal among modern life forms because any change in codon assignment would be highly deleterious. The frozen accident can be considered the default theory of code evolution because it does not imply any specific interactions between amino acids and the cognate codons or anticodons, or any particular properties of the code. The subsequent 49 years of code studies have elucidated notable features of the standard code, such as high robustness to errors, but failed to develop a compelling explanation for codon assignments. In particular, stereochemical affinity between amino acids and the cognate codons or anticodons does not seem to account for the origin and evolution of the code. Here, I expand Crick’s hypothesis on RNA-only translation system by presenting evidence that this early translation already attained high fidelity that allowed protein evolution. I outline an experimentally testable scenario for the evolution of the code that combines a distinct version of the stereochemical hypothesis, in which amino acids are recognized via unique sites in the tertiary structure of proto-tRNAs, rather than by anticodons, expansion of the code via proto-tRNA duplication, and the frozen accident.
Highlights
The time of this writing, early 2017, falls between two notable dates, the 100th anniversary of Francis Crick’s birth and the 50th anniversary of Crick’s 1968 classic paper on the evolution of the genetic code [1,2]
These results were taken as evidence of existence of an early stereochemical era in the code evolution during which the majority of the modern amino acids have been co-opted into the code [56]
It could be argued that frozen accident is not a theory and not even a hypothetical scenario but rather a meaningless nonexplanation of the code origin
Summary
The time of this writing, early 2017, falls between two notable dates, the 100th anniversary of Francis Crick’s birth and the 50th anniversary of Crick’s 1968 classic paper on the evolution of the genetic code [1,2]. Compared to Crick’s momentous contribution to the understanding of DNA structure and replication [3,4], and the principles of protein translation [5,6], the code evolution paper might seem to be almost inconsequential This masterpiece of conceptual thinking presents two ideas that have shaped the subsequent developments in the study of the code evolution and more generally, the study of the early evolution of life. The features of the code have been explored in detail and some aspects of its evolution seem to have been elucidated, these efforts appear to fall short of a compelling refutation of the frozen accident In this concept article, I briefly review the current understanding of the factors that determined the universality of the SGC and the three main scenarios of the code evolution. The goal is to place the frozen accident concept into the context of latest efforts in the field and briefly discuss some new ideas
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