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PubMed1992

The evolution of aminoacyl-tRNA synthetases, the biosynthetic pathways of amino acids and the genetic code.

In this paper the partition metric is used to compare binary trees deriving from (i) the study of the evolutionary relationships between aminoacyl-tRNA synthetases, (ii) the physicochemical properties of amino acids and (iii) the biosynthetic relationships between amino acids. If the tree defining the evolutionary relationships between aminoacyl-tRNA synthetases is assumed to be a manifestation of the mechanism that originated the organization of the genetic code, then the results appear to indicate the following: the hypothesis that regards the genetic code as a map of the biosynthetic relationships between amino acids seems to explain the organization of the genetic code, at least as plausibly as the hypotheses that consider the physicochemical properties of amino acids as the main adaptive theme that lead to the structuring of the code.

Amino Acids↗
PubMed1985

An unusual genetic code in nuclear genes of Tetrahymena.

We have cloned and partially sequenced two histone H3 genes of Tetrahymena thermophila. The DNA sequences strongly suggest that both genes are active in the vegetatively growing cell. Comparison of the derived amino acid sequences of these two genes with the actual sequence of Tetrahymena histone H3 results in the surprising conclusion that TAA codes for glutamine. This represents the first demonstration of a coding function for this termination codon of the "universal" code. This observation has important implications for the evolution of ciliates and of the genetic code.

Amino Acid Sequence↗
PubMed2026

The genetic code at the balance point of error and demand.

The origin and organizing principles of the genetic code remain central problems in molecular evolution. The low probability of the natural codon-to-amino acid mapping arising by chance has spurred the hypothesis that its structure is optimized for robustness to mutations and translational errors. For the construction of effective molecular machines, the repertoire of encoded amino acids must also be diverse enough in physicochemical features. Here, we examine whether the standard genetic code can be understood as a near-optimal solution balancing these two objectives: minimizing error load and aligning codon assignments with the naturally occurring amino acid composition. Using simulated annealing, we explore this trade-off across a broad range of parameters. We find that the standard genetic code resides near an optimum in the fitness landscape of possible genetic codes. The degeneracy of the code plays a dual role, minimizing mistranslation errors while matching codon multiplicity to amino acid usage frequencies. As a result, uniform codon usage alone is sufficient to recover the empirical amino acid composition, without any additional bias. It is a highly effective solution that balances fidelity against resource availability constraints. A comparative analysis of natural variants also reveals a functional decoupling: error robustness acts as a rigid global constraint determined by code topology, whereas compositional alignment serves as a more flexible variable that adapts to lineage-specific demands. These results support a multi-objective optimization framework in which the genetic code reflects a balance between translational fidelity and proteomic demand.

Genetic Code↗
PubMed1987

Codon usage in Homo sapiens: evidence for a coding pattern on the non-coding strand and evolutionary implications of dinucleotide discrimination.

This study reports the analysis of codon usage in 35 complete Homo sapiens genes. Both codon frequency and inter-codon interference exhibit patterns of evolutionary interest. There is a significant positive correlation between the frequency with which a given codon is used and the frequency with which its complement is used. Since the frequency of appearance of the complementary codon on the coding strand is equal to the frequency of appearance of the original codon on the non-coding strand, in the same phase, the non-coding strand is found to resemble the coding strand in triplet composition. The same effect has been observed in Escherichia coli. This preference for the use of certain complementary triplets as codons suggests that the evolution of the use of the genetic code depended to some extent upon the double-stranded nature of the coding material. In addition, the effect of discrimination against the use of two dinucleotides, CpG and UpA, is observed in codon usage and also in adjacent codon interference. Codons beginning with G, or A, are unlikely to be preceded by codons ending in C, or U, respectively. Consideration of codon assignment in the genetic code together with the observed CpG infrequency suggests that the evolution of the code may have been influenced by conditions in which the use of CpG dinucleotides was unfavorable. The infrequent use of UpA dinucleotides can be explained as the result of frameshift mutation during gene evolution.

Base Sequence↗
PubMed1987

Information theory and the genetic code.

The genetic code, which directs the protein biosynthesis, is an information system. Although all its details are not known at present, its essential characteristics are elucidated, as well for the replication or transcription as for the translation of the genetic message. A coherent picture now appears, which reveals the existence of an universal structure, the most fundamental features of which seem to obey some logic. A systematic approach has been devised, which aims to their integration in a theorectical scheme: many features of the code table can thus be interpreted as resulting from a unique principle of best resistance against the effects of mutations. Any group of triplets or amino-acids can be considered along this line. It is more difficult however, to analyse the coexistence of two (or more) different groups. In this work, we propose to extend our optimization principle into a more general one, which includes the notion of information as defined by Shannon. We explore some consequences of this new principle in the most simple models that one can build for the origin and evolution of the genetic code.

Genetic Code↗
PubMed1974

A proposed model for interaction of polypeptides with RNA.

Pairs of antiparallel beta polypeptide-chain segments in known protein structures are usually observed to form right-handed double helixes with helix parameters in the same range as those of nucleic acids. We have constructed a model containing only standard bond lengths, bond angles, and dihedral angles in which such a polypeptide double helix fits precisely into the minor groove of an RNA double helix with identical helix parameters. The geometry of the RNA portion is essentially a hybrid between those of the A and A' forms. Hydrogen bonds can be made between the ribose 2'-hydroxyls and polypeptide carbonyl oxygens. Since such precise complementarity between the stable conformations of RNA and polypeptides is unlikely to be merely coincidental, we propose that it played a fundamental role in the initiation of precellular evolution. Specificially, we propose that the two double-helical structures are mutually catalytic for assembly of one another from activated precursors in the prebiotic soup, and moreover that they provide some degree of genetic coding.

Biological Evolution↗
PubMedDate not supplied

[Neutral mutations and interference-stability of the genetic code].

The fundamental suggestions of the neutral theory of evolution are discussed. It is shown that the safety of the genetic code is expressed also in the thermostability of proteins, i.e. in their conformational mobility. There is no contradiction between the mutational changes of the protein thermostability and the neutral theory.

Genetic Code↗
PubMedDate not supplied

Entropy of the genetic information and evolution.

The entropy of the amino acid sequences coded by DNA is considered as a measure of diversity of variety of proteins, and is taken as a measure of evolution. The DNA or m-RNA sequence is considered as a stationary second-order Markov chain composed of four kinds of bases. Because of the biased nature of the genetic code table, increase of entropy of amino acid sequences is possible with biased nucleotide sequence. Thus the biased DNA base composition and the extreme rarity of the base doublet CpG of higher organisms are explained. It is expected that the amino acid composition was highly biased at the days of the origin of the genetic code table, and the more frequent amino acids have tended to get rarer, and the rarer ones more frequent. This tendency is observed in the evolution of hemoglobin, cytochrome C, fibrinopeptide, immunoglobulin and lysozyme, and protein as a whole.

Amino Acid Sequence↗
PubMed1979

Relative efficiency of anticodons in reading the valine codons during protein synthesis in vitro.

Using a protein synthesizing in vitro system programmed with MS 2-RNA, the relative efficiency (in the presence of each other) of valine tRNAs with the anticodons U*AC (U* represents 5-oxyacetic acid uridine monophosphate), GAC, and IAC to read the valine codons was investigated. An anticodon which can read all three positions of the codon according to the rules of Watson-Crick base-pairing and the wobble hypothesis is an order of magnitude more efficient than an anticodon which misreads the codon by reading only the first two positions and presumably disregards the third nucleotide of the codon. There are two seeming exceptions to this behavior: the anticodon U*AC reads the codon GUU quite efficiently and IAC is as effective as U*AC in reading the codon GUG. The significance of these exceptions is evaluated with respect to the organization and evolution of the genetic code.

Anticodon↗