Evolution of the genetic code: The ambiguity-reduction theory

Abstract

The experimental evidence has shown that the genetic code is based on arbitrary, or conventional, rules, in the sense that any codon can be associated to any amino acid, and this means that there is no deterministic link between them. This is in sharp contrast with the traditional paradigm of the stereochemical theory, which claims that the rules of the genetic code were determined by chemistry, and more precisely by stereochemical affinities between codons and amino acids. The discovery that the genetic code is based on arbitrary rules, on the other hand, raised a formidable problem: how can such rules exist in Nature? In order to deal with this problem, it has been pointed out that the rules of an arbitrary code could not come fully formed into existence. The first genetic code, in other words, was necessarily ambiguous, and its evolution took place with a mechanism that systematically reduced its ambiguity and eventually removed it. The concept of ambiguity-reduction has been repeatedly mentioned in the scientific literature, but very few papers have actually addressed the problem of its mechanism. One of these papers was published with the name of ribosome-oriented model in order to underline the key role that the ribosomal proteins had in that process, but later on it became clear that other factors had to be taken into account. This is why the ribosome-oriented model had to be extended and here a more general version is proposed with the name of ambiguity-reduction theory.