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PubMed1978

Evolution of a genetic code simulated with the computer.

A simple selforganizing model system of molecules is considered and it is demonstrated by a computer simulation, that a genetic code of 16 elements (aminoacids) can gradually be formed by such a system in the course of many generations. By a number of rare chance events, each suppressing other events of equal a priori probability, a single code results out of an immense number of possible codes of the same a priori probability. The result is discussed in relation to the uniqueness of the genetic code in living systems. The computer simulation emphasizes a particular step in a model pathway discussed elsewhere consisting of many assumed physicochemical steps leading to a genetic apparatus.

Base Sequence↗
PubMed1975

The origin of the genetic code.

A new approach to the origin of the genetic code is proposed based on some regularities in the nucleotide distribution pattern of the code. The relative amounts of various amino acids in primitive proteins were possibly different from those in organisms living today. The primordial ratio was supposed to shift to the modern one guided by the action of primitive nucleotides. Each primitive tRNA had a discriminator site and, distinguished from it, an anticodon site. It also postulated that primordially each amino acid could correspond to a wide variety of codons. During the course of the evolutionary change, a selective mechanism worked among the protobionts so that less frequent nucleotides became associated with more abundant amino acids in the primordial conditions,thus finally leading to the present codon catalogue.

Amino Acids↗
PubMed1991

[Hidden symmetry of the genetic code and laws of amino acid interaction].

Natural amino acids having common antiamino acids are divided into families and groups according to the algorithm of the genetic code (a-n-n-a, amino acid-codon-anticodon-antiamino acid). Members of these groups are placed symmetrically in the structure of the genetic code. In the course of evolution, those point mutations are predominantly accepted retained. In homologous proteins of phylogenetically related organisms which lend to amino acids belonging to one family or group and having common antiamino acids. This assumption is in agreement with L. B. Mekler's theory (1969) of the amino acid interaction code a-a.

Amino Acid Sequence↗
PubMed1975

A co-evolution theory of the genetic code.

The theory is proposed that the structure of the genetic code was determined by the sequence of evolutionary emergence of new amino acids within the primordial biochemical system.

Amino Acids↗
PubMed1989

The genetic code as a clue to understanding of molecular evolution.

The genetic code is comprised of a system concerning the distribution of doublets of the first two codon bases among amino acids. According to this system a definite order in the relative distribution of the first and the second codon bases coincides with a definite order among the common amino acids and their distribution for the number of hydrogen atoms per molecule (an unexpected parameter). The pattern of the relative distribution of the first and the second codon bases suggests it originated from a crystalline-like structure in which the set of bases AUGC served as an elementary structural unit and the base doublets played the role of structural analogs to the amino acids. These hypothetical crystalline-like aggregates are composed of the free molecules of amino acids and bases, and although different in their composition, should have an even number of hydrogen atoms per standard structural module.

Amino Acids↗
PubMed1989

Genetic code preferentially conserves long-range interactions among the amino acids.

The physical properties of amino acids were investigated in order to evaluate their possible relationship to the assignment of codons for amino acids in the genetic code. A comparison of the interconversion probability between amino acids and the distances between the amino acids for individual physical properties revealed a striking hierarchy among the physical properties. Surprisingly, it is the long-range/solvent interactions and not the short-range/stereochemical properties which are preferentially conserved in the genetic code.

Amino Acids↗
PubMed1975

Speculations on the evolution of the genetic code.

An evolutionary scheme is postulated in which the bases enter the genetic code in a definite temporal sequence and the correlated amino acids are assigned definite functions in the evolving system. The scheme requires a singlet code (guanine coding for glycine) evolving into a doublet code (guanine-cytosine doublet coding for gly (GG), ala (GC), arg (CG), pro (CC). The doublet code evolves into a triplet code. Polymerization of nucleotides is thought to have been by block polymerization rather than by a template mechanism. The proteins formed at first were simple structural peptides. No direct nucleotide-amino acid stereo-chemical interaction was required. Rather an adaptor-type indirect mechanism is thought to have been functioning since the origin.

Biological Evolution↗
PubMed1991

An RNA-amino acid complex and the origin of the genetic code.

The group I RNAs, of which the Tetrahymena ribosomal RNA intron is the most investigated example, catalyze their own splicing reactions. Splicing is initiated at a conserved site on the RNA that facilitates attack by exogenous guanosine (or its nucleotides) on the exon-intron junction. The guanosine site in the RNA's catalytic center also binds arginine, and is quite selective for the arginine side chain. This amino acid-RNA interaction is stereoselective, and L-arginine is preferred. Immediately at the site at which arginine binds there is one of only four RNA triplets in 92 group I RNA sequences: AGA/G and CGA/G. Thus the arginine contact site is within any of four different codons for arginine. Mutation of the conserved G in the middle of the triplet decreases affinity for the amino acid, showing that binding is sequence-specific. A pathway for the origin of the genetic code for arginine is suggested, based on the existence and properties of this sequence-specific, amino acid-specific RNA complex. The existence of a proto-ribosome related to the group I RNAs seems the most likely hypothesis. This notion is used to distinguish three periods in the development of the code. Restrained and exuberant hypotheses about the origin of the genetic code are distinguished, and some objections to these hypotheses are considered.

Animals↗
PubMed2026

Robust error-minimization in the genetic code across physicochemical metrics and variant codes: A graph-theoretic analysis in GF(2)6.

The standard genetic code reduces the impact of point mutations, but the robustness of this property across physicochemical metrics, naturally occurring variant codes, and codon-reassignment mechanisms remains incompletely quantified. Embedding the 64 codons in GF(2)6 represents the hypercube Q6 as a coordinate-dependent subgraph of the encoding-independent single-nucleotide mutation graph H(3,4), and enables continuous &#x3c1;-interpolation between the two. Under a quartet-pattern shuffle null (n=10,000), the standard code is significantly low-cost across four established, code-independent physicochemical distance metrics with partially overlapping content (Grant ham p=0.0062; Miyata p<0.001; Woese polar requirement p=0.003; Kyte-Doolittle hydropathy p=0.001), and the signal strengthens monotonically as &#x3c1; moves Q6&#x2192;H(3,4). A structure-aware sensitivity analysis under the alignment-derived ProtSub matrix (Jia & Jernigan 2021) yields the most extreme percentile of any measure tested (p=0.0004; all five p-values pass Bonferroni at &#x3b1;=0.05). Across the 27 NCBI translation tables, near-optimality is preserved: 11 of 12 informative-distance variants retain top-5% placement after BH-FDR correction. Natural codon reassignments avoid disrupting codon-family connectivity: under the encoding-independent H(3,4) adjacency, observed events are topology-breaking at relative risk 0.32 versus the candidate landscape (permutation p&#x2264;10-4). The H(3,4) result is stable by construction; the Q6 decomposition is representation-specific and fails to show depletion under 8 of 24 base-to-bit encodings, so we report H(3,4) as the primary test and Q6 as a sensitivity. Event-level conditional-logit modelling shows that topology avoidance and local physicochemical cost provide complementary, only weakly correlated signal (rs=0.15), and that topology adds explanatory value beyond physicochemistry under both Q6 and encoding-independent H(3,4) adjacency. Retrospective reanalysis of nine genome-recoding datasets is consistent with codon-family topology operating as an evolutionary-trajectory constraint distinct from acute engineering fitness. The contribution is the second axis: code evolution is jointly constrained by physicochemical smoothness and codon-family topological integrity, and these two constraints are partly independent.

Codon reassignment↗
PubMed1991

Rook's tour representation of the genetic code.

Disconnected recurrences of the stop signal, serine and arginine appear in the original representation of the genetic code, and of the stop signal, arginine, serine and leucine in the codon ring representation. To achieve connectedness along with structural continuity, a rook's tour representation is presented here. On the basis of structural similarities and disparities in their side groups, each of the 20 amino acids is associated with a domain comprised of from one to six contiguous squares on the chess board. As the rook moves on the chess board, it reaches all 64 squares in the ordering of the codon numbers, which prescribe the codons by a simple formula based on the position and size of the nucleotides in a triplet. Recurrences of the stop signal, arginine and serine occur naturally on the tour as the rook enters each of the latter domains for the second time. A mathematical equivalent of the rook's tour may enter as a programming device in the implementation of the code by the RNAs.

Amino Acids↗
PubMed1988

Transfer RNA genes and the genetic code in Chlamydomonas reinhardtii mitochondria.

Only three tRNA genes are present within a sequenced 12.35 kbp region of the 15.8 kbp mtDNA of Chlamydomonas reinhardtii, a unicellular green alga. The corresponding tRNAs, whose anticodons are specific for TGG (Trp), CAA/G (Gln) and ATG (Met) codons, all display conventional secondary structures. The tRNA(Met) gene encodes an elongator rather than initiator species. The standard genetic code is used in C. reinhardtii mitochondria, but codon distribution is highly biased: in a collection of six identified protein coding genes, nine codons (including TGA) are not used at all, while four other sense codons occur very infrequently. In spite of the absence of certain codons, a minimum of 23 tRNAs (assuming separate initiator and elongator tRNAs(Met) are used) is needed to translate the C. reinhardtii mitochondrial genetic code. It appears unlikely that this minimal tRNA set is encoded by C. reinhardtii mtDNA.

Base Sequence↗
PubMed1990

A generalized information function applied to the genetic code.

The problem of the partitioning of the degeneracy of the codons in the genetic code is considered in the framework of a generalized information function IG = c sigma kpk(ln pk + G(Ek] where k represents the number of codons in a specific degeneracy class and G(Ek) is an arbitrary real valued function. For G(Ek) = 0 the Shannon information function is recovered. For a particular choice of G(Ek) that takes the dominance of even degeneracies into account, it is found by direct numerical calculations that the correct degeneracy partitioning appears as optimal values of the Ig function. This results is also supported by optimization calculations in which the generalized information function is regarded as a continuous function in the degeneracy variables.

Amino Acids↗
PubMed1992

Ribosome-mediated incorporation of a non-standard amino acid into a peptide through expansion of the genetic code.

One serious limitation facing protein engineers is the availability of only 20 'proteinogenic' amino acids encoded by natural messenger RNA. The lack of structural diversity among these amino acids restricts the mechanistic and structural issues that can be addressed by site-directed mutagenesis. Here we describe a new technology for incorporating non-standard amino acids into polypeptides by ribosome-based translation. In this technology, the genetic code is expanded through the creation of a 65th codon-anticodon pair from unnatural nucleoside bases having non-standard hydrogen-bonding patterns. This new codon-anticodon pair efficiently supports translation in vitro to yield peptides containing a non-standard amino acid. The versatility of the ribosome as a synthetic tool offers new possibilities for protein engineering, and compares favourably with another recently described approach in which the genetic code is simply rearranged to recruit stop codons to play a coding role.

Amino Acid Sequence↗
PubMed1976

The evolution of a universal genetic code.

Some of the basic problems presented by the rapid evolution of a universal genetic code can be resolved by a mechanism of co-evolution of the code and the amino acids it serves.

Amino Acids↗
PubMed1988

Genetic code development by stop codon takeover.

A novel theoretical consideration of the origin and evolution of the genetic code is presented. Code development is viewed from the perspective of simultaneously evolving codons, anticodons and amino acids. Early code structure was determined primarily by thermodynamic stability considerations, requiring simplicity in primordial codes. More advanced coding stages could arise as biological systems became more complex and precise in their replication. To be consistent with these ideas, a model is described in which codons become permanently associated with amino acids only when a codon-anticodon pairing is strong enough to permit rapid translation. Hence all codons are essentially chain-termination or "stop" codons until tRNA adaptors evolve having the ability to bind tightly to them. This view, which draws support from several lines of evidence, differs from the prevalent thinking on code evolution which holds that codons specifying newer amino acids were derived from codons encoding older amino acids.

Amino Acids↗
PubMedDate not supplied

Consideration on the genetic code.

In this paper there are presented data and arguments which indicate that the genetic code also contains the information for the assembling of the trinucleotides and amino acids in the DNA-histones system, which works as an intra-cellar computer.

Genetic Code↗