Origin and evolution of the genetic code: The universal enigma

Abstract

The genetic code is nearly universal, and the arrangement of the codons in the standard codon table is highly non-random. The three main concepts on the origin and evolution of the code are the stereochemical theory, according to which codon assignments are dictated by physico-chemical affinity between amino acids and the cognate codons (anticodons); the coevolution theory, which posits that the code structure coevolved with amino acid biosynthesis pathways; and the error minimization theory under which selection to minimize the adverse effect of point mutations and translation errors was the principal factor of the code’s evolution. These theories are not mutually exclusive and are also compatible with the frozen accident hypothesis, i.e., the notion that the standard code might have no special properties but was fixed simply because all extant life forms share a common ancestor, with subsequent changes to the code, mostly, precluded by the deleterious effect of codon reassignment. Mathematical analysis of the structure and possible evolutionary trajectories of the code shows that it is highly robust to translational misreading but there are numerous more robust codes, so the standard code potentially could evolve from a random code via a short sequence of codon series reassignments. Thus, much of the evolution that led to the standard code could be a combination of frozen accident with selection for error minimization although contributions from coevolution of the code with metabolic pathways and weak affinities between amino acids and nucleotide triplets cannot be ruled out. However, such scenarios for the code evolution are based on formal schemes whose relevance to the actual primordial evolution is uncertain. A real understanding of the code origin and evolution is likely to be attainable only in conjunction with a credible scenario for the evolution of the coding principle itself and the translation system.

RNA–Amino Acid Binding: A Stereochemical Era for the Genetic Code

“…We accept the suggestion (Koonin and Novozhilov 2008) that random assignments in the manner of Crick's ''frozen accident'' (Crick 1968) are also consistent with concurrent stereochemistry, co-evolution, and adaptation; all four together may have shaped the ultimate 'universal' genetic code. Our best current summary of the implications of these data relies on multiply recurring trends that are unlikely to be radically revised by further experiments-a majority (&6/8, Table 1) of amino acids appear to have participated in a stereochemical era of coding assignment based on RNA-binding sites (Table 1; ), but a minority (&10/48, Table 1) of codons and anticodons for participating amino acids were directly assigned via such stereochemical associations.…”

“…(3) Some criticism was based on results with arginine peptides-as seen in parts I and II, peptides necessarily present a unique single-ended polar profile to RNA, and thus do not appear the same to RNA as free arginine. (Koonin and Novozhilov 2008) seemed also to rely on arginine results alone, and were apparently under the impression that RNA-amino acid interaction is too weak to be evolutionarily functional. This completely mistakes the data, summarized in Part II of this review.…”

A stretched conformation of DNA with a biological role?

“…No connection between triplet base conformation and origin of the genetic code has been proposed before, as far as we know, while RNA templating of amino acids has been speculated as a possible code origin in an RNA-world context (Koonin & Novozhilov, 2009;Yarus et al 2010). In support of our hypothesis of stacked base triplets as intrinsic recognition elements based on physical properties, we note that base-stacking arrangements also appear in mRNA/ribosome/tRNA complexes (Selmer et al 2006).…”

DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase

“…In the same way as for unstretched Watson-Crick base-paired DNA structures, we remark that the structure of the Σ phase is linked to function: the partitioning of bases into codons of three base pairs each is the first phase of operation of recombinase enzymes such as RecA, facilitating alignment of homologous or near-homologous sequences. By showing that this process does not require any very sophisticated manipulation of the DNA, we position it as potentially appearing as an early step in the development of life, and correlate the postulated sequence of incorporation of amino acids (phase 0 or 'the GADV world' (Ikehara et al 2002), phase 1 or 'GADVESPLIT' (Koonin & Novozhilov, 2009;Wong, 1975Wong, , 2005, then the remaining amino acids, CMFYHRKNQ), into molecular biology with the ease of Σ-formation for sequences including the associated codons. We also note that the machinery of nucleotide to peptide translation occurs necessarily with reference to triplets of bases, so that further investigation into the Σ phase of single and double strands of RNA and DNA might be a valuable source of insight into the origins not only of recombination, but also of gene expression.…”