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Universality in the Genetic Code
... One of the most celebrated arguments for UCA is based on the fact that the genetic code is identical , or nearly so, in all known life. The argument had been circling informally for some years before Hinegardner and Engelberg first presented it in detail20212223: ...
... If the code is not universal, the number of different codes should represent the number of different primordial ancestors … Hinegardner and Engelberg's reasoning hinges on the assumption that the genetic code is so important for fundamental genetic processes that any mutations in the code would be lethal. Carl Woese criticized this argument , noting its dependence on the assumption that the genetic code is a " historical accident " and must not be " chemically determined " [23]. Woese was a proponent of the " stereochemical hypothesis " , which holds that the association between a certain codon and its respective amino acid is dictated by chemical phenomena — that is, the observed code is required somehow by the laws of physics, perhaps by binding affinity of the nucleic acid codon to its corresponding amino acid23242526. ...
... Carl Woese criticized this argument , noting its dependence on the assumption that the genetic code is a " historical accident " and must not be " chemically determined " [23]. Woese was a proponent of the " stereochemical hypothesis " , which holds that the association between a certain codon and its respective amino acid is dictated by chemical phenomena — that is, the observed code is required somehow by the laws of physics, perhaps by binding affinity of the nucleic acid codon to its corresponding amino acid23242526. Woese was also sceptical that the code was " frozen " , and he postulated plausible mechanisms by which a degenerate code could evolve. If the code were somehow determined by physicochemical principles and evolvable, then multiple origins of life could conceivably converge independently on the same code. ...
The universal common ancestry (UCA) of all known life is a fundamental component of modern evolutionary theory, supported by a wide range of qualitative molecular evidence. Nevertheless, recently both the status and nature of UCA has been questioned. In earlier work I presented a formal, quantitative test of UCA in which model selection criteria overwhelmingly choose common ancestry over independent ancestry, based on a dataset of universally conserved proteins. These model-based tests are founded in likelihoodist and Bayesian probability theory, in opposition to classical frequentist null hypothesis tests such as Karlin-Altschul E-values for sequence similarity. In a recent comment, Koonin and Wolf (K&W) claim that the model preference for UCA is "a trivial consequence of significant sequence similarity". They support this claim with a computational simulation, derived from universally conserved proteins, which produces similar sequences lacking phylogenetic structure. The model selection tests prefer common ancestry for this artificial data set.
For the real universal protein sequences, hierarchical phylogenetic structure (induced by genealogical history) is the overriding reason for why the tests choose UCA; sequence similarity is a relatively minor factor. First, for cases of conflicting phylogenetic structure, the tests choose independent ancestry even with highly similar sequences. Second, certain models, like star trees and K&W's profile model (corresponding to their simulation), readily explain sequence similarity yet lack phylogenetic structure. However, these are extremely poor models for the real proteins, even worse than independent ancestry models, though they explain K&W's artificial data well. Finally, K&W's simulation is an implementation of a well-known phylogenetic model, and it produces sequences that mimic homologous proteins. Therefore the model selection tests work appropriately with the artificial data.
For K&W's artificial protein data, sequence similarity is the predominant factor influencing the preference for common ancestry. In contrast, for the real proteins, model selection tests show that phylogenetic structure is much more important than sequence similarity. Hence, the model selection tests demonstrate that real universally conserved proteins are homologous, a conclusion based primarily on the specific nested patterns of correlations induced in genetically related protein sequences.
This article was reviewed by Rob Knight, Robert Beiko (nominated by Peter Gogarten), and Michael Gilchrist.
... Towards analyzing the middle stage of the evolution of the SGC The evolutionary origin of the standard genetic code (SGC) is widely viewed as a central open problem in the evolution of life [1][2][3][4]. Key questions in the field focus on early steps in the evolution of the SGC, such as: what is the origin of the first tRNA and what is the amino acid that it encoded; how did this first tRNA give rise to a set of 20 encoded amino acids? ...
... As a result, the SGC is quite stable. This concept has become well known as part of the frozen accident theory [8], but actually is older [23] (also see [4]). The principle that a feature that is in general use cannot be lost without severe consequences was elaborated more recently [24]. ...
Based on (i) an analysis of the regularities in the standard genetic code and (ii) comparative genomics of the anticodon modification machinery in the three branches of life, we derive the tRNA set and its anticodon modifications as it was present in LUCA. Previously we proposed that an early ancestor of LUCA contained a set of 23 tRNAs with unmodified anticodons that was capable of translating all 20 amino acids while reading 55 of the 61 sense codons of the standard genetic code (SGC). Here we use biochemical and genomic evidence to derive that LUCA contained a set of 44 or 45 tRNAs containing 2 or 3 modifications while reading 59 or 60 of the 61 sense codons. Subsequent tRNA modifications occurred independently in the Bacteria and Eucarya, while the Archaea have remained quite close to the tRNA set as it was present in LUCA.
... Mechanistic investigations later solidified that ribosomes synthesize protein by directionally transiting mRNA in discrete, three-nucleotide codon steps using specific aminoacylated transfer RNA (aa-tRNA) substrates [5]. This conserved protein synthesis mechanism defines the genetic code linking mRNA and protein sequence in all organisms [6][7][8]. ...
Since the framing of the Central Dogma, it has been speculated that physically distinct ribosomes within cells may influence gene expression and cellular physiology. While heterogeneity in ribosome composition has been reported in bacteria, protozoans, fungi, zebrafish, mice and humans, its functional implications remain actively debated. Here, we review recent evidence demonstrating that expression of conserved variant ribosomal DNA (rDNA) alleles in bacteria, mice and humans renders their actively translating ribosome pool intrinsically heterogeneous at the level of ribosomal RNA (rRNA). In this context, we discuss reports that nutrient limitation-induced stress in Escherichia coli leads to changes in variant rRNA allele expression, programmatically altering transcription and cellular phenotype. We highlight that cells expressing ribosomes from distinct operons exhibit distinct drug sensitivities, which can be recapitulated in vitro and potentially rationalized by subtle perturbations in ribosome structure or in their dynamic properties. Finally, we discuss evidence that differential expression of variant rDNA alleles results in different populations of ribosome subtypes within mammalian tissues. These findings motivate further research into the impacts of rRNA heterogeneities on ribosomal function and predict that strategies targeting distinct ribosome subtypes may hold therapeutic potential.
This article is part of the discussion meeting issue ‘Ribosome diversity and its impact on protein synthesis, development and disease’.
... The standard genetic code, which is a mapping of 64 codons to 20 standard amino acids and the translation stop signal, is shared, with minor modifications only, by all life forms on earth (Woese, Hinegardner et al. 1964;Woese 1967;Ycas 1969;Osawa 1995). The apparent universality of the code implies that the last universal common ancestor (LUCA) of all extant life forms should have already possessed, together with a complex translation machinery, the same genetic code as contemporary organisms. ...
We investigated the error-minimization properties of putative primordial codes that consisted of 16 supercodons, with the third base being completely redundant, using a previously derived cost function and the error minimization percentage as the measure of a code's robustness to mistranslation. It is shown that, when the 16-supercodon table is populated with 10 putative primordial amino acids, inferred from the results of abiotic synthesis experiments and other evidence independent of the code evolution, and with minimal assumptions used to assign the remaining supercodons, the resulting 2-letter codes are nearly optimal in terms of the error minimization level. The results of the computational experiments with putative primordial genetic codes that contained only two meaningful letters in all codons and encoded 10 to 16 amino acids indicate that such codes are likely to have been nearly optimal with respect to the minimization of translation errors. This near-optimality could be the outcome of extensive early selection during the co-evolution of the code with the primordial, error-prone translation system, or a result of a unique, accidental event. Under this hypothesis, the subsequent expansion of the code resulted in a decrease of the error minimization level that became sustainable owing to the evolution of a high-fidelity translation system.
... Shortly after the genetic code of Escherichia coli was deciphered (Nirenberg et al. 1963), it was recognized that this particular mapping of 64 codons to 20 amino acids and two punctuation marks (start and stop signals) is shared, with relatively minor modifications, by all known life forms on earth (Hinegardner and Engelberg 1963;Woese, Hinegardner, and Engelberg 1964). (Woese et al. 1966b), which is a measure of an amino acid's hydrophobicity: the greater hydrophobicity the darker the shading (the stop codons are shaded black). ...
The genetic code is nearly universal, and the arrangement of the codons in the standard codon table is highly non-random. The three main concepts on origin and evolution of the code are the stereochemical theory; the coevolution theory; and the error minimization theory. These theories are not mutually exclusive and are also compatible with the frozen accident hypothesis. Mathematical analysis of the structure and possible evolutionary trajectories of the code shows that it is highly robust to translational error but there is a huge number of more robust codes, so that the standard code potentially could evolve from a random code via a short sequence of codon series reassignments. Thus, much of the evolution that led to the standard code can be interpreted as a combination of frozen accident with selection for translational error minimization although contributions from coevolution of the code with metabolic pathways and/or weak affinities between amino acids and nucleotide triplets cannot be ruled out. However, such scenarios for the code evolution are based on formal schemes whose relevance to the actual primordial evolution is uncertain, so much caution in interpretation is necessary. A real understanding of the code's origin and evolution is likely to be attainable only in conjunction with a credible scenario for the evolution of the coding principle itself and the translation system.
... The genetic code is characterized by four "letters", which represent four different nitrogenous bases or nucleotides, two purine bases: adenine (A), guanine (G), and two pyrimidine bases: cytosine (C) and thymine (T). The order in the sequential arrangement of the nucleotides constitutes the genetic information, which is translated via the genetic code into the corresponding amino acids [3,4]. Using groups of three nucleotides (codon), it is possible to obtain 4 3 = 64 different codons, sufficient to encode the 20 amino acids that characterize the language on which a protein is defined. ...
The genetic code table represents a fundamental scheme to translate a genetic code into a sequence of amino acids and, therefore, the possibility of operating the synthesis of all the proteins necessary for the life of organisms. Unfortunately, the various biological mechanisms are not fully clear. Hence, in this report, we analyzed the genetic code table and the amino acids codified by codons with an original theoretical and statistical approach based on the concept of permutations. We found an interesting reinterpretation of many codons, as reverse codons, which could help clarify some as-yet-unknown aspects in the field of protein folding.
... Such irreversibility is evident in the 'core algorithms' of life on Earth that we observe to stretch back, largely unaltered, in deep time [6]. Examples include the universality of a four-letter genetic code [23,24]; the universality of ATP synthase as a disequilibrium converting engine and ATP as an energy transfer molecule [25,26] and the widespread use of the RuBisCO enzyme in carbon fixation, the gateway for the vast majority of carbon assimilation on present-day Earth [27,28]. Once these innovations emerged, the advantages they confer 'freeze' them into the evolutionary threads of life (e.g. ...
Previous studies show that city metrics having to do with growth, productivity and overall energy consumption scale superlinearly , attributing this to the social nature of cities. Superlinear scaling results in crises called ‘singularities’, where population and energy demand tend to infinity in a finite amount of time, which must be avoided by ever more frequent ‘resets’ or innovations that postpone the system's collapse. Here, we place the emergence of cities and planetary civilizations in the context of major evolutionary transitions. With this perspective, we hypothesize that once a planetary civilization transitions into a state that can be described as one virtually connected global city, it will face an ‘asymptotic burnout’, an ultimate crisis where the singularity-interval time scale becomes smaller than the time scale of innovation. If a civilization develops the capability to understand its own trajectory, it will have a window of time to affect a fundamental change to prioritize long-term homeostasis and well-being over unyielding growth—a consciously induced trajectory change or ‘homeostatic awakening’. We propose a new resolution to the Fermi paradox: civilizations either collapse from burnout or redirect themselves to prioritizing homeostasis, a state where cosmic expansion is no longer a goal, making them difficult to detect remotely.
... The standard genetic code is known to be highly efficient in minimizing the effects of mistranslation errors and point mutations [15][16][17][18] . This optimality is prominent among theories regarding the origin of the genetic code [19][20][21][22] . ...
Ocean microbes are responsible for about 50% of primary production on Earth, but selective forces governing their evolution are not well understood. We studied evolutionary conservation by examining single-nucleotide variants in the marine environment, and discovered strong purifying selection exerted across marine microbial genes. We show evidence demonstrating that this selection is driven by the environment, and especially by nitrogen availability. We further corroborate that nutrient availability drives this 'resource-driven' selection by showing stronger selection on highly expressed and extracellular genes, that are more resource-consuming. Finally, we show that the standard genetic code, along with amino acid abundances, facilitate nutrient conservation through robustness to mutations that increase nitrogen and carbon consumption. Notably, this optimization also applies to multiple taxa across all domains of Life, including the Human genome, and it manifests in code structure. Overall, we uncover overwhelmingly strong purifying selective pressure across marine microbial life that may have contributed to the structure of our genetic code.
... What is most extraordinary, however, is that the rules of the genetic code are virtually identical in all living creatures (Hinegardner and Engelberg 1963;Woese et al. 1964). A few exceptions do exist but they are very minor changes and occur in an infinitesimal number of organisms. ...
There are currently three major theories on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and the error-minimization theory. The first two assume that the genetic code originated respectively from chemical affinities and from metabolic relationships between codons and amino acids. The error-minimization theory maintains that in primitive systems the apparatus of protein synthesis was extremely prone to errors, and postulates that the genetic code evolved in order to minimize the deleterious effects of the translation errors. This article describes a fourth theory which starts from the hypothesis that the ancestral genetic code was ambiguous and proposes that its evolution took place with a mechanism that systematically reduced its ambiguity and eventually removed it altogether. This proposal is distinct from the stereochemical and the coevolution theories because they do not contemplate any ambiguity in the genetic code, and it is distinct from the error-minimization theory because ambiguity-reduction is fundamentally different from error-minimization. The concept of ambiguity-reduction has been repeatedly mentioned in the scientific literature, but so far it has remained only an abstract possibility because no model has been proposed for its mechanism. Such a model is described in the present article and may be the first step in a new approach to the study of the evolution of the genetic code.
... Shortly after the genetic code was deciphered, it was recognized that the meaning of each codon is the same in most known organisms [9] . Furthermore, key components of the protein translation system, including a nearly complete set of 20 aminoacyl-tRNA synthetases, one for each amino acid, are universal [10,11] . ...
Over the past decade, genetic encoding of non-canonical amino acids (ncAAs) into proteins has emerged as a powerful tool in protein engineering. Recent progresses focus mostly on the incorporation of two or more ncAAs by using stop codon suppression methodologies, but little work has been done to recode one or more sense codons. The first part of this thesis describes follow up experiments to test whether an heterologous methionyl-tRNA synthetase (MetRS)/tRNAMet pair from an archeaon behaves orthogonal in Escherichia coli for the simultaneous incorporation of the methionine (Met) analogues azidohomoalanine (Aha) and ethionine (Eth) in response to the starting and internal sense codons, respectively. We determined that this was not the case. Therefore, other established orthogonal pairs were tested, of which the Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS) pair was found as the most promising candidate. Next, a new selection system based on amber stop codon suppression in the pfkA (phosphofructokinase I) gene was developed and optimized to screen an MmPylRS library. Upon screening, a mutant that was able to incorporate Met in response to stop codons was isolated. Further optimization of this system will allow the incorporation of Met analogues into targeted locations. In the second part of this thesis, the site-specific incorporation of ncAAs by amber codon suppression was explored to generate multiple sites for protein bioconjugation and immobilization. The lipase from Thermoanaerobacter thermohydrosulfuricus (TTL) was used as model protein because lipases are one of the most versatile biocatalysts employed in the industry. Two E. coli strains lacking release factor I (RF1) were evaluated for their suppression efficiencies at single and multiple amber codons in comparison with a standard expression strain. High incorporation of N-Propargyl-Lysine (Plk) was achieved at a specific permissive position on the TTL surface using a RF1-deficient strain, whereas suppression at multiple positions was suboptimal and dependent on the orthogonal pair, ncAA and expression vector employed. Incorporation of the ncAA Plk into TTL endowed the enzyme with an alkyne group for bioconjugation without impairing its activity. The alkyne group was then selectively and efficiently conjugated to azide-biotin via copper-catalyzed azide-alkyne cycloaddition (CuAAC), with retention of enzymatic activity. Attempts to achieve direct immobilization of biotinyl-TTL on Strep-Tactin® beads as well as alkynyl-TTL on azide-agarose beads, although unsuccessful, provided some insights that will guide further optimization endeavors. In summary, this work describes the first efforts towards the development of a genetic selection system for the reassignment of the Met sense N-terminal and internal codons to two different ncAAs in E. coli. It also provides insights into the potential use of site-specific incorporation of ncAAs into proteins and biocatalysts for applications such as bioconjugation and immobilization.
... Soon after Escherichia coli genetic code was deciphered [1] and found to be almost universal [2], many hypotheses have been proposed to explain how the standard genetic code (SGC) evolved among the huge number of possible alternatives [3][4][5][6][7][8][9]. Indeed, the limited number of SGC exceptions has been fully characterized [10] as well as species-specific biases in the use of SGC codon repertoire [11][12]. ...
Genetic code redundancy would yield, on the average, the assignment of three codons for each of the natural amino acids. The fact that this number is observed only for incorporating Ile and to stop RNA translation still waits for an overall explanation. Through a Structural Bioinformatics approach, the wealth of information stored in the Protein Data Bank has been used here to look for unambiguous clues to decipher the rationale of standard genetic code (SGC) in assigning from one to six different codons for amino acid translation. Leu and Arg, both protected from translational errors by six codons, offer the clearest clue by appearing as the most abundant amino acids in protein-protein and protein-nucleic acid interfaces. Other SGC hidden messages have been sought by analyzing, in a protein structure framework, the roles of over- and under-protected amino acids.
... Elucidating the structure of DNA (Watson and Crick, 1953) led to identification of the nucleotide triplets that comprise the genetic code (Crick, 1955;Crick et al., 1961), its universality (Woese, 1965(Woese, , 1964, discovery of how codons are transcribed into mRNA (Martin et al., 1962), and the pathways by which mRNA is translated into a protein (Nirenberg, 1965(Nirenberg, , 1963. Codons are nucleotide triplets, comprised of four bases adenine (A), cytosine (C) guanine (G) and thymine (T). ...
... 5,6 In late 1960 he initiated research on the genetic code, and over the next few years made fundamental contributions to our understanding of its origin, universality, and specificity. He was among the first to consider translation in an explicitly evolutionary perspective [7][8][9] and emphasized the role of RNA, for example in refocusing the basis of genetic code specificity away from steric interactions among amino acids: "in an important sense, the codon 'chooses' its amino acid, not the reverse." 10 Through these early years, the structure of RNAs remained unclear; indeed, not until the early 1960s was it established that RNAs were linear polymers, i.e., can be referred to as having a sequence. In the early 1950s, Fred Sanger and collaborators had developed a stepwise experimental strategy to reveal the structure of insulin as a sequence of amino acids. ...
From 1971 to 1985, Carl Woese and colleagues generated oligonucleotide catalogs of 16S/18S rRNAs from more than 400 organisms. Using these incomplete and imperfect data, Carl and his colleagues developed unprecedented insights into the structure, function, and evolution of the large RNA components of the translational apparatus. They recognized a third domain of life, revealed the phylogenetic backbone of bacteria (and its limitations), delineated taxa, and explored the tempo and mode of microbial evolution. For these discoveries to have stood the test of time, oligonucleotide catalogs must carry significant phylogenetic signal; they thus bear re-examination in view of the current interest in alignment-free phylogenetics based on k-mers. Here we consider the aims, successes, and limitations of this early phase of molecular phylogenetics. We computationally generate oligonucleotide sets (e-catalogs) from 16S/18S rRNA sequences, calculate pairwise distances between them based on D 2 statistics, compute distance trees, and compare their performance against alignment-based and k-mer trees. Although the catalogs themselves were superseded by full-length sequences, this stage in the development of computational molecular biology remains instructive for us today.
... The standard genetic code, which is a mapping of 64 codons to 20 standard amino acids and the translation stop signal, is shared, with minor modifications only, by all life forms on earth1234. The apparent universality of the code implies that the last universal common ancestor (LUCA) of all extant life forms should have already possessed , together with a complex translation machinery, the same genetic code as contemporary organisms. ...
Background:
The standard genetic code is redundant and has a highly non-random structure. Codons for the same amino acids typically differ only by the nucleotide in the third position, whereas similar amino acids are encoded, mostly, by codon series that differ by a single base substitution in the third or the first position. As a result, the code is highly albeit not optimally robust to errors of translation, a property that has been interpreted either as a product of selection directed at the minimization of errors or as a non-adaptive by-product of evolution of the code driven by other forces.
Results:
We investigated the error-minimization properties of putative primordial codes that consisted of 16 supercodons, with the third base being completely redundant, using a previously derived cost function and the error minimization percentage as the measure of a code's robustness to mistranslation. It is shown that, when the 16-supercodon table is populated with 10 putative primordial amino acids, inferred from the results of abiotic synthesis experiments and other evidence independent of the code's evolution, and with minimal assumptions used to assign the remaining supercodons, the resulting 2-letter codes are nearly optimal in terms of the error minimization level.
Conclusion:
The results of the computational experiments with putative primordial genetic codes that contained only two meaningful letters in all codons and encoded 10 to 16 amino acids indicate that such codes are likely to have been nearly optimal with respect to the minimization of translation errors. This near-optimality could be the outcome of extensive early selection during the co-evolution of the code with the primordial, error-prone translation system, or a result of a unique, accidental event. Under this hypothesis, the subsequent expansion of the code resulted in a decrease of the error minimization level that became sustainable owing to the evolution of a high-fidelity translation system.
Reviewers:
This article was reviewed by Paul Higgs (nominated by Arcady Mushegian), Rob Knight, and Sandor Pongor. For the complete reports, go to the Reviewers' Reports section.
... Shortly after the genetic code of Escherichia coli was deciphered (Nirenberg et al. 1963), it was recognized that this particular mapping of 64 codons to 20 amino acids and two punctuation marks (start and stop signals) is shared, with relatively minor modifications, by all known life forms on earth (Hinegardner and Engelberg 1963;Woese, Hinegardner, and Engelberg 1964). (Woese et al. 1966b), which is a measure of an amino acid's hydrophobicity: the greater hydrophobicity the darker the shading (the stop codons are shaded black). ...
The expansion of the standard code according to the coevolution theory. Phase 1 amino acids are orange, and phase 2 amino acids are green. The numbers show the order of amino acid appearance in the code according to (99). The arrows define 13 precursor-product pairs of amino acids, their color defines the biosynthetic families of Glu (blue), Asp (dark-green), Phe (magenta), Ser (red), and Val (light-green). See Origin and Evolution of the Genetic Code: The Universal Enigma by Koonin and Novozhilov, pp. 99-111.
In this chapter, the genetic codeGenetic code seems to be a universal codeUniversal code. The universal codeUniversal code has a specific arrangement of the codonsCodon that is definitely not random. There are at least three major concepts of the origin and the evolutionEvolution of the universal genetic codeGenetic code: Firstly, there is the stereochemical theoryStereochemical theory stating that the assignments of codonsCodon are determined by the physicochemical affinity of the amino acidsAmino acids and the cognate codonsCodon (synonymously referred to as anticodons)Anticodons; secondly, the co-evolution theory stating that the structure of the code structure coevolved with the biosynthesis process of amino acids; and thirdly, the error minimization theoryError minimization theory stating that there is a selection pressure minimizing the negative effects of point mutations and errors in translationTranslation were the main factor of code development. These theories are not contradictory and are also in line with the frozen accident hypothesis, such as the idea that the standard code may not have any special properties, but is simply determined by the fact that all existing life forms have a common ancestorCommon ancestor, whereby later alterations to the code are generally excluded by the detrimental effect of codonCodon reallocation. The mathematical examination of the structure and potential evolutionary trajectories of the code reveals that the code is highly resistant to translationTranslation errors, although there are numerous more resistant codes, suggesting that the standard code could emerge from a random code through a short sequence of rearrangements of series of codonsCodon. A large proportion of the evolutionEvolution leading to the standard code seems to be a mixture of a frozen collision with a selection for error minimization, even though it cannot be excluded that the code co-evolves along with metabolic pathways due to weak affinities between amino acidsAmino acids and nucleotide triplets. These scenarios for code evolution, nonetheless, are founded on formal patterns with uncertain relevance to real primordial evolutionEvolution. A true comprehension of code origins and developments is probably only possible in connection with a plausible script for the development of the coding scheme and the translationTranslation tool itself.
DNA contains the genetic code, which provides complete information about the synthesis of proteins in every living cell. Each gene encodes for a corresponding protein but most of the DNA sequence is non-coding. In addition to this non-coding part of the DNA, there is another redundancy, namely a multiplicity of DNA triplets (codons) corresponding to code for a given amino acid. In this paper we investigate possible physical reasons for the coding redundancy, by exploring free energy considerations and abundance probabilities as potential insights.
Hier soll nur auf die Bildung der Polynukleotide aus Mononukleotiden eingegangen werden (zur Biosynthese der Basen, der Ribose und der Nukleotide bzw. der Nukleosidmono-, di- und -triphosphate s. Glock 1955, Reichard 1955, Schlenk 1955, Buchanan 1960, Crosbie 1960, Michelson 1963).
Part I of this paper deals with the amount of degeneracy in the genetic code or, looked at in reverse, the amount of nonsense. Section A considers the experimental evidence and suggests (a) that technical difficulties have prevented assigning meaning to the still unassigned triplets and (b) that the validity of the earlier evidences for nonsense triplets may be questioned in the light of recent discoveries. Complete degeneracy of the code and total absence of nonsense have not yet been excluded. Section B comes to the conclusion, on the basis of general evolutionary considerations, that natural selection would be expected to establish and preserve a completely degenerate code. Section C points out that different nondegenerate codes differ greatly in the builtin frequency of nonsense mutations by single base substitutions.
Nucleotide sequences of 50 RNA codons recognized by amphibian and mammalian liver transfer RNA preparations were determined
and compared with those recognized by Escherichia coli transfer RNA. Almost identical translations were obtained with transfer
RNA from guinea pig liver, Xenopus laevis liver (South African clawed toad), and E. coli. However, guinea pig and Xenopus transfer RNA differ markedly from E. coli
transfer RNA in relative response to certain trinucleotides. Transfer RNA from mammalian liver, amphibian liver, and amphibian
muscle respond similarly to trinucleotide codons. Thus the genetic code is essentially universal, but transfer RNA from one
organism may differ from that of another in relative response to some codons.
The Sequence Hypothesis states that the amino acid sequence of a protein is determined by the sequence of nucleotides in some particular piece of nucleic acid. The evidence in favor of this is now very considerable, and hopes that this relationship may be a simple one and that the sequence of the four bases in the nucleic acid can be thought of as a simple code for the amino acid sequence. The exact sequence of bases that determines each of the twenty amino acids found in proteins is known as the “coding problem.” The amount of degeneracy may be small andthe evidence from the cell-free system, the amino acid replacement data, and the fractionation of sRNA, is compatible with this. The amount of degeneracy may be very much higher and this is suggested by the wide range of DNA composition and by the genetic studies. Also,it is not contradicted by the more direct evidence, though this suggests that if the code is highly degenerate it is unlikely to be degenerate at random. The chapter concludes that there have been dramatic developments in this field and it now seems possible that the code will be found within a comparatively short time. The chapter deals with the recent progress and discusses the general nature of the genetic code.
A cell-free system that incorporates amino acids into polypeptide has been prepared from extracts of the alga Chlamydomonas. The addition of polyuridylic acid to this system stimulates the incorporation both of phenylalanine and of leucine.
THE characteristics by which organisms are recognized are the expressions of the information contained in their nucleic acids. As such, a knowledge of their DNA base composition, or if possible the base sequences of some organisms, should be a valuable asset in their classification. Lee, Wahl and Barbu1were the first to recognize the taxonomic importance of analysing the average DNA base compositions of micro-organisms. While the overall base compositions of some unrelated organisms may be the same, this equivalence would appear to be a minimum requirement for extensive base sequence homologies2and genetic compatibility (except in certain cases of F-duction3). Thus, similar DNA base compositions in two organisms might indicate close relationships whereas dissimilar base compositions would indicate that the organisms are unrelated.
A mutation in the genetic code would place new amino acids in certain loci and entirely eliminate amino acids from other loci of practically all proteins in an organism. It is reasonable to postulate that mutations of this kind cannot supplant the original code. The genetic code, once established, would therefore remain invariant.