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At least 109 records · Page 6Linked to original sources
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↗
PubMed1994

On the syntactic structure and redundancy distribution of the genetic code.

By means of an algorithm for finding rules in data, it is shown that the genetic code may be written as a codon-tree, independent of amino acid assignments. Considering this tree as a structural description, a low-complexity, context-free grammar of the code is built and its grammar complexity and grammar redundancy calculated. The relationship between the codon-tree and the hierarchy of amino acid categorizations previously introduced by the author is investigated. Interpreting the obtained code's structure as a record of its evolution, some inferences about the divergences of the code series are made.

Algorithms↗
PubMed1995

The phylogeny of tRNAs seems to confirm the predictions of the coevolution theory of the origin of the genetic code.

An extensive analysis of the evolutionary relationships existing between transfer RNAs, performed using parsimony algorithms, is presented. After building up an estimate of the tRNA ancestral sequences, these sequences are then compared using certain methods. The results seem to suggest that the coevolution hypothesis (Wong, J.T., 1975, Proc. Natl. Acad. Sci. USA 72, 1909-1912) that sees the genetic code as a map of the biosynthetic relationships between amino acids is further supported by these results, as compared to the hypotheses that see the physicochemical properties of amino acids as the main adaptative theme that led to the structuring of the genetic code.

Amino Acid Sequence↗
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↗
PubMed1980

The genetic code in bovine mitochondria: sequence of genes for the cytochrome oxidase subunit II and two tRNAs.

Bovine-heart mitochondrial DNA from a single animal was isolated and fragments representative of the entire genome cloned into multicopy plasmid vectors to facilitate determination of its complete nucleotide sequence. We present here the sequence of the region covering the gene for cytochrome oxidase subunit II. Comparison of this sequence with the amino acid sequence of the homologous beef-heart protein has enabled the determination of most of the bovine mitochondrial genetic code. The code differs from the "universal" genetic code in that UGA codes for tryptophan and not termination, and AUA codes for methionine and not isoleucine. The only codon family not represented is the AGA/AGG pair normally used for arginine; evidence from other genes suggests that these code for termination in bovine mitochondria. The sequence presented also includes the adjacent tRNAAsp and tRNALys genes. The tRNAAsp gene is separated by one nucleotide from the 5' end of the COII gene and only three bases separate the 3' end of this gene and the adjacent tRNALys gene. This highly compact gene organisation is very similar to that found in the corresponding region of the human mitochondrial genome and the gene arrangement is identical. The structure of the respective bovine and human tRNAs vary primarily the "D-" and "T psi C-loops".

Animals↗
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↗
PubMed1991

A quantitative measure of error minimization in the genetic code.

We have calculated the average effect of changing a codon by a single base for all possible single-base changes in the genetic code and for changes in the first, second, and third codon positions separately. Such values were calculated for an amino acid's polar requirement, hydropathy, molecular volume, and isoelectric point. For each attribute the average effect of single-base changes was also calculated for a large number of randomly generated codes that retained the same level of redundancy as the natural code. Amino acids whose codons differed by a single base in the first and third codon positions were very similar with respect to polar requirement and hydropathy. The major differences between amino acids were specified by the second codon position. Codons with U in the second position are hydrophobic, whereas most codons with A in the second position are hydrophilic. This accounts for the observation of complementary hydropathy. Single-base changes in the natural code had a smaller average effect on polar requirement than all but 0.02% of random codes. This result is most easily explained by selection to minimize deleterious effects of translation errors during the early evolution of the code.

Amino Acids↗