A change from nonsense to sense in the genetic code.
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Codon, Nonsense↗
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Natural variation in the genetic code.
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Animals↗
Experimental studies on the origin of the genetic code and the process of protein synthesis: a review update.
This article is an update of our earlier review (Lacey and Mullins, 1983) in this journal on the origin of the genetic code and the process of protein synthesis. It is our intent to discuss only experimental evidence published since then although there is the necessity to mention the old enough to place the new in context. We do not include theoretical nor hypothetical treatments of the code or protein synthesis. Relevant data regarding the evolution of tRNAs and the recognition of tRNAs by aminoacyl-tRNA-synthetases are discussed. Our present belief is that the code arose based on a core of early assignments which were made on a physico-chemical and anticodonic basis and this was expanded with new assignments later. These late assignments do not necessarily show an amino acid-anticodon relatedness. In spite of the fact that most data suggest a code origin based on amino acid-anticodon relationships, some new data suggesting preferential binding of Arg to its codons are discussed. While information regarding coding is not increasing very rapidly, information regarding the basic chemistry of the process of protein synthesis has increased significantly, principally relating to aminoacylation of mono- and polyribonucleotides. Included in those studies are several which show stereoselective reactions of L-amino acids with nucleotides having D-sugars. Hydrophobic interactions definitely play a role in the preferences which have been observed.
5'-Nucleotidase↗
Evolution of amino acid frequencies in proteins over deep time: inferred order of introduction of amino acids into the genetic code.
To understand more fully how amino acid composition of proteins has changed over the course of evolution, a method has been developed for estimating the composition of proteins in an ancestral genome. Estimates are based upon the composition of conserved residues in descendant sequences and empirical knowledge of the relative probability of conservation of various amino acids. Simulations are used to model and correct for errors in the estimates. The method was used to infer the amino acid composition of a large protein set in the Last Universal Ancestor (LUA) of all extant species. Relative to the modern protein set, LUA proteins were found to be generally richer in those amino acids that are believed to have been most abundant in the prebiotic environment and poorer in those amino acids that are believed to have been unavailable or scarce. It is proposed that the inferred amino acid composition of proteins in the LUA probably reflects historical events in the establishment of the genetic code.
Amino Acid Sequence↗
On the classes of aminoacyl-tRNA synthetases and the error minimization in the genetic code.
As a consequence of the existence of two classes of aminoacyl-tRNA synthetases (aaRSs), we defined two types of mutations: g (mutations that do not change the class of the involved amino acids) and u (those which change the class). We have found that the mean chemical distance resulting from g mutations is smaller than that corresponding to u mutations, indicating that g mutations are responsible for most of the known minimization of the genetic code. This supports models for the origin and evolution of the code, in which new amino acids were added after duplications or modification of existing aaRSs.
Amino Acids↗
Structural basis for orthogonal tRNA specificities of tyrosyl-tRNA synthetases for genetic code expansion.
The archaeal/eukaryotic tyrosyl-tRNA synthetase (TyrRS)-tRNA(Tyr) pairs do not cross-react with their bacterial counterparts. This 'orthogonal' condition is essential for using the archaeal pair to expand the bacterial genetic code. In this study, the structure of the Methanococcus jannaschii TyrRS-tRNA(Tyr)-L-tyrosine complex, solved at a resolution of 1.95 A, reveals that this archaeal TyrRS strictly recognizes the C1-G72 base pair, whereas the bacterial TyrRS recognizes the G1-C72 in a different manner using different residues. These diverse tRNA recognition modes form the basis for the orthogonality. The common tRNA(Tyr) identity determinants (the discriminator, A73 and the anticodon residues) are also recognized in manners different from those of the bacterial TyrRS. Based on this finding, we created a mutant TyrRS that aminoacylates the amber suppressor tRNA with C34 65 times more efficiently than does the wild-type enzyme.
Amino Acid Sequence↗
[The meaning of the genetic code: reconstruction of the stage of prebiologic evolution].
According to a certain order in sets of the two first codon bases, 20 common amino acids can be divided into 5 families each containing 4 amino acids; the corresponding order in the distribution of codon bases can be easily detected, if common amino acids are distributed for the numbers of hydrogen atoms per molecule (Sukhodolets, 1980). In the present paper, the order in the distribution of codon bases is explained on the basis of the hypothesis claiming the prebiological existence of crystalline associates composed of amino acids and bases as free molecules. In these heterogeneous crystalline associates amino acids were analogs to the base douplets and the arrangement of molecules followed a certain rule, namely: 40 protons per molecular complex forming a standard structural compartment. It is proposed that the crystalline associates existed as lyotropic liquid crystals with hydrocarbons as solvent. The genetical code allows to discover two different original crystallization types for bases and amino acids. Therefore, the life possibly originates from combining in the same structure different crystallization patterns, which resulted in formation of a finite crystalline associate.
Amino Acid Sequence↗
A stereochemical relationship could explain the origin of the genetic code.
A stereochemical analysis has been carried out to investigate the possible complementarity between an RNA double helix containing thymine instead of uracil and two growing peptide chains. It is found that the optimal interactions follow the rules of the genetic code. The nature of the interaction could allow a mechanism for aminoacyl-RNA formation which could have given rise to the tRNA ancestors. Some theoretical implications are discussed.
Drug Interactions↗
Possibility of genetic coding of amino acid sequences by coherent electronic states in nucleotide chains.
The concept of coherent electronic states and coherent interactions in supramolecular structures is applied to the process of genetic information coding and its transcription from DNA to mRNA. A new genetic code is proposed based on the assumption of coherent electron states in linear chains of nucleotide bases. A new interpretation of codon equivalency (redundancy) is given. The number of existing amino acids is derived from the optimalization principle applied to the physical system storing the genetic information in the new code. The proposed code uses a variable number of positions or nucleotide bases along the DNA-mRNA structure to code a single amino acid in a protein. The average of this variable number must be equal to the base of natural logarithms (e = 2.7 . . .) in order to minimize the number of nucleotides required to code a sequence of amino acids.
Amino Acid Sequence↗
Expansion of the genetic code in yeast: making life more complex.
Proteins account for the catalytic and structural versatility displayed by all cells, yet they are assembled from a set of only 20 common amino acids. With few exceptions, only 61 nucleotide triplets also direct incorporation of these amino acids. Endeavors to expand the genetic code recently progressed to nucleus-containing cells, after Chin et al.1 transferred Escherichia coli genes for a mutant tyrosine-adaptor molecule and its synthetase into Saccharomyces cerevisiae. Transformed yeast cells were produced that exhibit efficient site-specific incorporation of non-biotic amino acids into proteins. This makes it likely that code complexity can be elevated experimentally in mammals.
Amino Acids↗
Evolutionary implication of genetic code deviations.
We formulate the following hypothesis: Life's origin may have occurred during the lower Archaean at a time when the environmental temperature was higher than it is at present. Preliminary consequences of this hypothesis are studied from the point of view of molecular evolution. We restrict our attention to implications regarding the genetic code. We conclude that alternative assignment of termination codons may be understood in terms of: (a) the elevated temperatures to which the progenote may initially have been exposed; and (b) the subsequent response of its genome to the opportunity provided by the eventual loss of hyperthermal genetic expression during a thermal transition (TT) period, which was triggered off by the evolution of the dynamic Earth.
Biological Evolution↗
[Use of the degeneracy of the genetic code by selective pressure to cut up genes of procaryote genomes].
The DNA sequences of three bacteriophages are analysed in order to localise those parts coding for a protein. A weak stability on the DNA molecule allows us to characterize the beginning and the end of genes. A survey of the codons used shows that the cause for this weak stability is the systematic use of A-T bases in third position, which is made possible by the degeneracy of the genetic code.
Bacteriophage phi X 174↗
Forces maintaining organellar genomes: is any as strong as genetic code disparity or hydrophobicity?
It remains controversial why mitochondria and chloroplasts retain the genes encoding a small subset of their constituent proteins, despite the transfer of so many other genes to the nucleus. Two candidate obstacles to gene transfer, suggested long ago, are that the genetic code of some mitochondrial genomes differs from the standard nuclear code, such that a transferred gene would encode an incorrect amino acid sequence, and that the proteins most frequently encoded in mitochondria are generally very hydrophobic, which may impede their import after synthesis in the cytosol. More recently it has been suggested that both these interpretations suffer from serious "false positives" and "false negatives": genes that they predict should be readily transferred but which have never (or seldom) been, and genes whose transfer has occurred often or early, even though this is predicted to be very difficult. Here I consider the full known range of ostensibly problematic such genes, with particular reference to the sequences of events that could have led to their present location. I show that this detailed analysis of these cases reveals that they are in fact wholly consistent with the hypothesis that code disparity and hydrophobicity are much more powerful barriers to functional gene transfer than any other. The popularity of the contrary view has led to the search for other barriers that might retain genes in organelles even more powerfully than code disparity or hydrophobicity; one proposal, concerning the role of proteins in redox processes, has received widespread support. I conclude that this abandonment of the original explanations for the retention of organellar genomes has been premature. Several other, relatively minor, obstacles to gene transfer certainly exist, contributing to the retention of relatively many organellar genes in most lineages compared to animal mtDNA, but there is no evidence for obstacles as severe as code disparity or hydrophobicity. One corollary of this conclusion is that there is currently no reason to suppose that engineering nuclear versions of the remaining mammalian mitochondrial genes, a feat that may have widespread biomedical relevance, should require anything other than sequence alterations obviating code disparity and causing modest reductions in hydrophobicity without loss of enzymatic function.
Animals↗
RNA editing: trypanosomes rewrite the genetic code.
The understanding of how genetic information is stored and expressed has advanced considerably since the "central dogma" asserted that genetic information flows from the nucleotide sequence of DNA to that of messenger RNA (mRNA) which in turn specifies the amino acid sequence of a protein. It was found that genetic information can be stored as RNA (e.g. in RNA viruses) and can flow from RNA to DNA by reverse transcriptase enzyme activity. In addition, some genes contain introns, nucleotide sequences that are removed from their RNA (by RNA splicing) and thus are not represented in the resultant protein. Furthermore, alternative splicing was found to produce variant proteins from a single gene. More recently, the study of trypanosome parasites revealed an unexpected and indeed counter-intuitive genetic complexity. Genetic information for a single protein can be dispersed among several (DNA) genes in these organisms. One of these genes specifies an encrypted precursor mRNA that is converted to a functional mRNA by a process called RNA editing that inserts and deletes uridylate nucleotides. The sequence of the edited mRNA is specified by multiple small RNAs, named guide RNAs, (gRNAs) each of which is encoded in a separate gene. Thus, edited mRNA sequences are assembled from multiple genes by the transfer of information from one type of RNA to another. The existence of editing was surprising but has stimulated the discovery of other types of RNA editing. The Stuart laboratory has been exploring RNA editing in trypanosomes from the time of its discovery. They found dramatic differences between the mitochondrial gene sequences and those of the corresponding mRNAs, which indicated editing by the insertion and deletion of uridylates. Some editing was modest; simply eliminating shifts in sequence register of minimally extending the protein coding sequence. However, editing of many mRNAs was startingly extensive. The RNA sequence was essentially entirely remodeled with its sequence more the result of editing than the gene sequence. The identities of genes for such extensively edited RNA were not recognizable from the DNA sequence but they were readily identifiable from the edited mRNA sequence. Thus, despite the complex and extensive editing the resultant mRNA sequence is precise. Characterization of partially edited RNAs indicated that editing proceeds in the direction opposite to that used to specify the protein which reflects the use of the gRNAs. The numerous gRNAs that are used for editing are encoded in the DNA molecules whose role was previously a mystery. Using information gained in our earlier studies, the Stuart group developed an in vitro system that reproduces the fundamental process of editing in order to resolve the mechanism by which it occurs. They determined that editing entails a series of enzymatic steps rather than the mechanism used in RNA splicing. They also showed that chimeric gRNA-mRNA molecules are aberrant by-products of editing rather than intermediates in the process as had been proposed. Additional studies are exploring precisely how the number of added and deleted uridylates is specified by the gRNA. The Stuart laboratory showed that editing is performed by an aggregation of enzymes that catalyze the separate steps of editing. It also developed a method to purify this multimolecule complex that contains several, perhaps tens of, proteins. This will allow the study of its composition and the functions of its component parts. Indeed, the gene for one component has been identified and its detailed characterization begun. These studies are developing tools to explore related processes. An early finding in the lab was that the various mRNAs are differentially edited during the life cycle of the parasite. The pattern of this editing indicates that editing serves to regulate the alternation between two modes of energy generation. This regulation is coordinated with other events that are occurring during the life c
Animals↗
A supersymmetric model for the evolution of the genetic code.
A model is presented for the structure and evolution of the eukaryotic and vertebrate mitochondrial genetic codes, based on the representation theory of the Lie superalgebra A(5,0) approximately sl(6/1). A key role is played by pyrimidine and purine exchange symmetries in codon quartets.
Animals↗
The history of deciphering the genetic code: setting the record straight.
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Genetic Code↗
[ON THE GENETIC CODE. CONCLUSIONS ON THE GENERAL NATURE OF THE CODE RESULTING FROM BIOCHEMICAL EXPERIMENTS].
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DNA↗
The genetic code of a squid mitochondrial gene.
Cytochrome oxidase subunit I gene of a squid (Mollusca), Doryteuthis mitochondrial genome was sequenced. Comparison with the nucleotide sequence and the deduced amino acid sequence of other animal mitochondria suggests that the squid mitochondria has a variation in the genetic code; UGA codes for tryptophan, AUA for methionine and AGA/G for serine. This situation is similar to the case of Drosophila or Ascaris mitochondria.
Amino Acid Sequence↗