A Minimum Principle in Codon-Anticodon Interaction

Imposing a minimum principle in the framework of the so called crystal basis model of the genetic code, we determine the structure of the minimum set of anticodons which allows the translational-transcription for animal mitochondrial code. The results are in very good agreement with the observed anticodons.Comment: 13 pages, 6 Tables, to appear in Biosystem

Symmetry and Minimum Principle at the Basis of the Genetic Code

The importance of the notion of symmetry in physics is well established: could it also be the case for the genetic code? In this spirit, a model for the Genetic Code based on continuous symmetries and entitled the "Crystal Basis Model" has been proposed a few years ago. The present paper is a review of the model, of some of its first applications as well as of its recent developments. Indeed, after a motivated presentation of our mathematical model, we illustrate its pertinence by applying it for the elaboration and verification of sum rules for codon usage probabilities, as well as for establishing relations and some predictions between physical-chemical properties of amino-acids. Then, defining in this context a "bio-spin" structure for the nucleotides and codons, the interaction between a couple of codon-anticodon can simply be represented by a (bio) spin-spin potential. This approach will constitute the second part of the paper where, imposing the minimum energy principle, an analysis of the evolution of the genetic code can be performed with good agreement with the generally accepted scheme. A more precise study of this interaction model provides informations on codon bias, consistent with data.Comment: To appear in BIOMAT 2016, 326 - 362, 201

A Realistic Model under which the Genetic Code is Optimal

The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the Mean Square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By comparing this value with a distribution of values belonging to codes generated by random permutations of amino acid assignments, the level of error robustness of a genetic code can be quantified. We present a calculation in which the standard genetic code is shown to be optimal. We obtain this result by (1) using recently updated values of polar requirement as input; (2) fixing seven assignments (Ile, Trp, His, Phe, Tyr, Arg, and Leu) based on aptamer considerations; and (3) using known biosynthetic relations of the 20 amino acids. This last point is reflected in an approach of subdivision (restricting the random reallocation of assignments to amino acid subgroups, the set of 20 being divided in four such subgroups). The three approaches to explain robustness of the code (specific selection for robustness, amino acid-RNA interactions leading to assignments, or a slow growth process of assignment patterns) are reexamined in light of our findings. We offer a comprehensive hypothesis, stressing the importance of biosynthetic relations, with the code evolving from an early stage with just glycine and alanine, via intermediate stages, towards 64 codons carrying todays meaning.Comment: 22 pages, 3 figures, 4 tables Journal of Molecular Evolution, July 201

Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position.

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5'- and 3'-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix

The transition from noncoded to coded protein synthesis: did coding mRNAs arise from stability-enhancing binding partners to tRNA?

<p>Abstract</p> <p>Background</p> <p>Understanding the origin of protein synthesis has been notoriously difficult. We have taken as a starting premise Wolf and Koonin's view that "evolution of the translation system is envisaged to occur in a compartmentalized ensemble of replicating, co-selected RNA segments, i.e., in an RNA world containing ribozymes with versatile activities".</p> <p>Presentation of the hypothesis</p> <p>We propose that coded protein synthesis arose from a noncoded process in an RNA world as a natural consequence of the accumulation of a range of early tRNAs and their serendipitous RNA binding partners. We propose that, initially, RNA molecules with 3' CCA termini that could be aminoacylated by ribozymes, together with an ancestral peptidyl transferase ribozyme, produced small peptides with random or repetitive sequences. Our concept is that the first tRNA arose in this context from the ligation of two RNA hairpins and could be similarly aminoacylated at its 3' end to become a substrate for peptidyl transfer catalyzed by the ancestral ribozyme. Within this RNA world we hypothesize that proto-mRNAs appeared first simply as serendipitous binding partners, forming complementary base pair interactions with the anticodon loops of tRNA pairs. Initially this may have enhanced stability of the paired tRNA molecules so they were held together in close proximity, better positioning the 3' CCA termini for peptidyl transfer and enhancing the rate of peptide synthesis. If there were a selective advantage for the ensemble through the peptide products synthesized, it would provide a natural pathway for the evolution of a coding system with the expansion of a cohort of different tRNAs and their binding partners. The whole process could have occurred quite unremarkably for such a profound acquisition.</p> <p>Testing the hypothesis</p> <p>It should be possible to test the different parts of our model using the isolated contemporary 50S ribosomal subunit initially, and then with RNAs transcribed <it>in vitro </it>together with a minimal set of ribosomal proteins that are required today to support protein synthesis.</p> <p>Implications of the hypothesis</p> <p>This model proposes that genetic coding arose <it>de novo </it>from complementary base pair interactions between tRNAs and single-stranded RNAs present in the immediate environment.</p> <p>Reviewers</p> <p>This article was reviewed by Eugene Koonin, Rob Knight and Berthold Kastner (nominated by Laura Landweber).</p

Molecular Simulations of the Ribosome and Associated Translation Factors

The ribosome is a macromolecular complex which is responsible for protein synthesis in all living cells according to their transcribed genetic information. Using X-ray crystallography and, more recently, cryo-electron microscopy (cryo-EM), the structure of the ribosome was resolved at atomic resolution in many functional and conformational states. Molecular dynamics simulations have added information on dynamics and energetics to the available structural information, thereby have bridged the gap to the kinetics obtained from single-molecule and bulk experiments. Here, we review recent computational studies that brought notable insights into ribosomal structure and function.Comment: 11 pages, 3 figures, to be published in Current Opinion in Structural Biolog