Phenotypic Graphs and Evolution Unfold the Standard Genetic Code as the Optimal

In this work, we explicitly consider the evolution of the Standard Genetic Code (SGC) by assuming two evolutionary stages, to wit, the primeval RNY code and two intermediate codes in between. We used network theory and graph theory to measure the connectivity of each phenotypic graph. The connectivity values are compared to the values of the codes under different randomization scenarios. An error-correcting optimal code is one in which the algebraic connectivity is minimized. We show that the SGC is optimal in regard to its robustness and error-tolerance when compared to all random codes under different assumptions.     

An Extended RNA Code and its Relationship to the Standard Genetic Code: An Algebraic and Geometrical Approach

An algebraic and geometrical approach is used to describe the primaeval RNA code and a proposed Extended RNA code. The former consists of all codons of the type RNY, where R means purines, Y pyrimidines, and N any of them. The latter comprises the 16 codons of the type RNY plus codons obtained by considering the RNA code but in the second (NYR type), and the third, (YRN type) reading frames. In each of these reading frames, there are 16 triplets that altogether complete a set of 48 triplets, which specify 17 out of the 20 amino acids, including AUG, the start codon, and the three known stop codons. The other 16 codons, do not pertain to the Extended RNA code and, constitute the union of the triplets YYY and RRR that we define as the RNA-less code. The codons in each of the three subsets of the Extended RNA code are represented by a four-dimensional hypercube and the set of codons of the RNA-less code is portrayed as a four-dimensional hyperprism. Remarkably, the union of these four symmetrical pairwise disjoint sets comprises precisely the already known six-dimensional hypercube of the Standard Genetic Code (SGC) of 64 triplets. These results suggest a plausible evolutionary path from which the primaeval RNA code could have originated the SGC, via the Extended RNA code plus the RNA-less code. We argue that the life forms that probably obeyed the Extended RNA code were intermediate between the ribo-organisms of the RNA World and the last common ancestor (LCA) of the Prokaryotes, Archaea, and Eucarya, that is, the cenancestor. A general encoding function, E, which maps each codon to its corresponding amino acid or the stop signal is also derived. In 45 out of the 64 cases, this function takes the form of a linear transformation F, which projects the whole six-dimensional hypercube onto a four-dimensional hyperface conformed by all triplets that end in cytosine. In the remaining 19 cases the function E adopts the form of an affine transformation, i.e., the composition of F with a particular translation. Graphical representations of the four local encoding functions and E, are illustrated and discussed. For every amino acid and for the stop signal, a single triplet, among those that specify it, is selected as a canonical representative. From this mapping a graphical representation of the 20 amino acids and the stop signal is also derived. We conclude that the general encoding function E represents the SGC itself.     

On Error Minimization in a Sequential Origin of the Standard Genetic Code

Distances between amino acids were derived from the polar requirement measure of amino acid polarity and Benner and co-workers' (1994) 74-100 PAM matrix. These distances were used to examine the average effects of amino acid substitutions due to single-base errors in the standard genetic code and equally degenerate randomized variants of the standard code. Second-position transitions conserved all distances on average, an order of magnitude more than did second-position transversions. In contrast, first-position transitions and transversions were about equally conservative. In comparison with randomized codes, second-position transitions in the standard code significantly conserved mean square differences in polar requirement and mean Benner matrix-based distances, but mean absolute value differences in polar requirement were not significantly conserved. The discrepancy suggests that these commonly used distance measures may be insufficient for strict hypothesis testing without more information. The translational consequences of single-base errors were then examined in different codon contexts, and similarities between these contexts explored with a hierarchical cluster analysis. In one cluster of codon contexts corresponding to the RNY and GNR codons, second-position transversions between C and G and transitions between C and U were most conservative of both polar requirement and the matrix-based distance. In another cluster of codon contexts, second-position transitions between A and G were most conservative. Despite the claims of previous authors to the contrary, it is shown theoretically that the standard code may have been shaped by position-invariant forces such as mutation and base content. These forces may have left heterogeneous signatures in the code because of differences in translational fidelity by codon position. A scenario for the origin of the code is presented wherein selection for error minimization could have occurred multiple times in disjoint parts of the code through a phyletic process of competition between lineages. This process permits error minimization without the disruption of previously useful messages, and does not predict that the code is optimally error-minimizing with respect to modern error. Instead, the code may be a record of genetic process and patterns of mutation before the radiation of modern organisms and organelles. Received: 28 July 1997 / Accepted: 23 January 1998     

Genetic Code Mutations: The Breaking of a Three Billion Year Invariance

The genetic code has been unchanging for some three billion years in its canonical ensemble of encoded amino acids, as indicated by the universal adoption of this ensemble by all known organisms. Code mutations beginning with the encoding of 4-fluoro-Trp by Bacillus subtilis, initially replacing and eventually displacing Trp from the ensemble, first revealed the intrinsic mutability of the code. This has since been confirmed by a spectrum of other experimental code alterations in both prokaryotes and eukaryotes. To shed light on the experimental conversion of a rigidly invariant code to a mutating code, the present study examined code mutations determining the propagation of Bacillus subtilis on Trp and 4-, 5- and 6-fluoro-tryptophans. The results obtained with the mutants with respect to cross-inhibitions between the different indole amino acids, and the growth effects of individual nutrient withdrawals rendering essential their biosynthetic pathways, suggested that oligogenic barriers comprising sensitive proteins which malfunction with amino acid analogues provide effective mechanisms for preserving the invariance of the code through immemorial time, and mutations of these barriers open up the code to continuous change.     

The Evolution of the Genetic Code Revisited

The evolution of the genetic code in terms of the adoption of new codons has previously been related to the relative thermostability of codon–anticodon interactions such that the most stable interactions have been hypothesised to represent the most ancient coding capacity. This derivation is critically dependent on the accuracy of the experimentally determined stability parameters. A new set of parameters recently determined for B-DNA reveals that the codon–anticodon pairs for the codes in non-plant mitochondria on the one hand and prokaryotic and eukaryotic organisms on the other can be unequivocally divided into two classes – the most stable base steps define a common code specified by the first two bases in a codon while the less stable base steps correlate with divergent usage and the adoption of a 3-letter code. This pattern suggests that the fixation of codons for A, G, P, V, S, T, D/E, R may have preceded the divergence of the non-plant mitochondrial line from other organisms. Other variations in the code correlate with the least stable codon–anticodon pairs. Presented at: National Workshop on Astrobiology: Search for Life in the Solar System, Capri, Italy, 26 to 28 October, 2005.     

Factors in Protobiomonomer Selection for the Origin of the Standard Genetic Code

Acta Biotheoretica - Natural selection of specific protobiomonomers during abiogenic development of the prototype genetic code is hindered by the diversity of structural, spatial, and rotational...     

Comparative Analysis of Asteraceae Chloroplast Genomes: Structural Organization,RNA Editing and Evolution

Plant Molecular Biology Reporter - Comparative chloroplast genome analysis presents new opportunities for performing molecular phylogeny studies and revealing the significant evolutionary features...     

Evolution of the Genetic Triplet Code via Two Types of Doublet Codons

Explaining the apparent non-random codon distribution and the nature and number of amino acids in the ‘standard’ genetic code remains a challenge, despite the various hypotheses so far proposed. In this paper we propose a simple new hypothesis for code evolution involving a progression from singlet to doublet to triplet codons with a reading mechanism that moves three bases each step. We suggest that triplet codons gradually evolved from two types of ambiguous doublet codons, those in which the first two bases of each three-base window were read (‘prefix’ codons) and those in which the last two bases of each window were read (‘suffix’ codons). This hypothesis explains multiple features of the genetic code such as the origin of the pattern of four-fold degenerate and two-fold degenerate triplet codons, the origin of its error minimising properties, and why there are only 20 amino acids. Reviewing Editor: Dr. Laura Landweber An erratum to this article can be found at .     

Introns: Mighty Elements from the RNA World

The discovery of RNA-based enzymatic activity by Thomas Cechs and Sidney Altmans laboratories was a momentous event that led Walter Gilbert to the concept of an RNA world—a primitive ancient stage of life that existed before the appearance of DNA and protein molecules. A year later, Gilbert formulated the exon theory of genes, which hypothesized that introns are very ancient genetic elements present at the earliest stages of life in the RNA world. This theory has been fiercely debated and still has vigorous supporters and opponents. In this communication, we explore peculiarities in the RNA-protein world and their effect on intron–exon structures. We demonstrate that these peculiarities, which exist in the absence of DNA, could shed light on introns original functions as well as the important role they might have played in the origin of life. For ancient DNA-lacking cells, a crucial problem existed in distinguishing two distinct subsets of RNAs: those messenger molecules coding for proteins and those heritable genetic molecules complementary to messenger RNAs that propagate the genetic information through generations. We propose that ancient introns could act as markers of RNA subsets, directing them to different functions.Reviewing Editor: Dr. Manyuan Long     

Chitinases Encoded in the Genomes of Acidobacteria: Origin and Evolution

Microbiology - Acidobacteria are one of the widespread and numerically abundant groups of prokaryotes in soils and peatlands. The functional potential of these microorganisms remains poorly...     

The Early Phases of Genetic Code Origin: Conjectures on the Evolution of Coded Catalysis

A review of the most significant contributions on the early phases of genetic code origin is presented. After stressing the importance of the key intermediary role played in protein synthesis, by peptidyl-tRNA, which is attributed with a primary function in ancestral catalysis, the general lines leading to the codification of the first amino acids in the genetic code are discussed. This is achieved by means of a model of protoribosome evolution which sees protoribosome as the central organiser of ancestral biosynthesis and the mediator of the encounter between compounds (metabolite-pre-tRNAs) and catalysts (peptidyl-pre-tRNAs). The encounter between peptidyl-pre-tRNA catalysts in protoribosome is favoured by metabolic pre-mRNAs and later resulted (given the high temperature at which this evolution is supposed to have taken place) in the evolution of mRNAs with codons of the type GNS. These mRNAs codified only for those amino acids that the coevolution theory of genetic code origin sees as the precursors of all other amino acids. Some aspects of the model here discussed might be rendered real by the transfer-messenger RNA molecule (tmRNA) which is here considered a molecular fossil of ancestral protein synthesis.