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1.
A multivariate study of the relationship between the genetic code and the physical-chemical properties of amino acids 总被引:5,自引:0,他引:5
Summary The 20 naturally occurring amino acids are characterized by 20 variables: pKNH
2, pKCOOH, pI, molecular weight, substituent van der Waals volume, seven1H and13C nuclear magnetic resonance shift variables, and eight hydrophobicity-hydrophilicity scales. The 20-dimensional data set is reduced to a few new dimensions by principal components analysis. The three first principal components reveal relationships between the properties of the amino acids and the genetic code. Thus the amino acids coded for by adenosine (A), uracil (U), or cytosine (C) in their second codon position (corresponding to U, A, or G in the second anticodon position) are grouped in these components. No grouping was detected for the amino acids coded for by guanine (G) in the second codon position (corresponding to C in the second anticodon position). The results show that a relationship exists between the physical-chemical properties of the amino acids and which of the A (U), U (A), or C (G) nucleotide is used in the second codon (anticodon) position. The amino acids coded for by G (C) in the second codon (anticodon) position do not participate in this relationship. 相似文献
2.
Extension of the genetic code for the introduction of nonnatural amino acids into proteins was examined by using five-base codon–anticodon pairs. A streptavidin mRNA containing a CGGUA codon at the Tyr54 position and a tRNAUACCG chemically aminoacylated with a nonnatural amino acid were added to an Escherichia coli in vitro translation system. Western blot analysis indicated that the CGGUA codon is decoded by the aminoacyl-tRNA containing the UACCG anticodon. HPLC analysis of the tryptic fragment of the translation product revealed that the nonnatural amino acid was incorporated corresponding to the CGGUA codon without affecting the reading frame adjacent to the CGGUA codon. Another 15 five-base codons CGGN1N2, where N1 and N2 indicate one of four nucleotides, were also successfully decoded by aminoacyl-tRNAs containing the complementary five-base anticodons. These results provide a novel strategy for nonnatural mutagenesis as well as a novel insight into the mechanism of frameshift suppression. 相似文献
3.
Breaking the degeneracy of the genetic code via sense codon reassignment has emerged as a way to incorporate multiple copies of multiple non-canonical amino acids into a protein of interest. Here, we report the modification of a normally orthogonal tRNA by a host enzyme and show that this adventitious modification has a direct impact on the activity of the orthogonal tRNA in translation. We observed nearly equal decoding of both histidine codons, CAU and CAC, by an engineered orthogonal M. jannaschii tRNA with an AUG anticodon: tRNAOpt. We suspected a modification of the tRNAOptAUG anticodon was responsible for the anomalous lack of codon discrimination and demonstrate that adenosine 34 of tRNAOptAUG is converted to inosine. We identified tRNAOptAUG anticodon loop variants that increase reassignment of the histidine CAU codon, decrease incorporation in response to the histidine CAC codon, and improve cell health and growth profiles. Recognizing tRNA modification as both a potential pitfall and avenue of directed alteration will be important as the field of genetic code engineering continues to infiltrate the genetic codes of diverse organisms. 相似文献
4.
By introducing a mutational deterioration functionMD and a principle of approximate minimum of the function, we have deduced the distribution of amino acids in genetic code, which includes the degenracy rule of codons, the global extreme of genetic code from codon interactions and the hydrophobicity domain of the prevalent (standard) code.The project supported by National Science Foundation of China. 相似文献
5.
D Grafstein 《Journal of theoretical biology》1983,105(1):157-174
The origin of the genetic code may be attributed to a postulated prebiological stereochemistry in which amino acid dimers, the trans -R,R'-diketopiperazines, interacted with prototype codon and anticodon nucleotide sequences. An intricately coupled stereochemistry is formulated which displays a binary logic for amino acid-codon recognition. It is shown that the diketopiperazine ring system can be inserted between any terminal pair of base paired nucleotides in a codon-anticodon structure with exact registration of complementary hydrogen bonding functional groups. This yields a codon-dimer-anticodon structure in which each amino acid residue is projected towards and interacts with a particular sequence of vicinal nucleotides on either codon or anticodon. The projection direction and the sequence of nucleotides encountered is a strongly coupled function of the choice of codon terminal nucleotide and the handedness of the amino acid. The reciprocal chemical nature of the complementary base pairs drives the selection of dimers containing quite dissimilar and chirally opposed amino acids. Application of the stereochemical model to the in vivo system leads to a general correlation for amino acid-codon assignments. The genetic code is restated in terms of the dimers selected. The profound symmetry of the code is elucidated and this proves useful for correlative and predictive purposes. 相似文献
6.
7.
Thomas Cavalier-Smith 《Journal of molecular evolution》2001,53(4-5):555-595
I attempt to sketch a unified picture of the origin of living organisms in their genetic, bioenergetic, and structural aspects.
Only selection at a higher level than for individual selfish genes could power the cooperative macromolecular coevolution
required for evolving the genetic code. The protein synthesis machinery is too complex to have evolved before membranes. Therefore
a symbiosis of membranes, replicators, and catalysts probably mediated the origin of the code and the transition from a nucleic
acid world of independent molecular replicators to a nucleic acid/protein/lipid world of reproducing organisms. Membranes
initially functioned as supramolecular structures to which different replicators attached and were selected as a higher-level
reproductive unit: the proto-organism. I discuss the roles of stereochemistry, gene divergence, codon capture, and selection
in the code's origin. I argue that proteins were primarily structural not enzymatic and that the first biological membranes
consisted of amphipathic peptidyl-tRNAs and prebiotic mixed lipids. The peptidyl-tRNAs functioned as genetically-specified
lipid analogues with hydrophobic tails (ancestral signal peptides) and hydrophilic polynucleotide heads. Protoribosomes arose
from two cooperating RNAs: peptidyl transferase (large subunit) and mRNA-binder (small subunit). Early proteins had a second
key role: coupling energy flow to the phosphorylation of gene and peptide precursors, probably by lithophosphorylation by
membrane-anchored kinases scavenging geothermal polyphosphate stocks. These key evolutionary steps probably occurred on the
outer surface of an `inside out-cell' or obcell, which evolved an unambiguous hydrophobic code with four prebiotic amino acids
and proline, and initiation by isoleucine anticodon CAU; early proteins and nucleozymes were all membrane-attached. To improve
replication, translation, and lithophosphorylation, hydrophilic substrate-binding and catalytic domains were later added to
signal peptides, yielding a ten-acid doublet code. A primitive proto-ecology of molecular scavenging, parasitism, and predation
evolved among obcells. I propose a new theory for the origin of the first cell: fusion of two cup-shaped obcells, or hemicells,
to make a protocell with double envelope, internal genome and ribosomes, protocytosol, and periplasm. Only then did water-soluble
enzymes, amino acid biosynthesis, and intermediary metabolism evolve in a concentrated autocatalytic internal cytosolic soup,
causing 12 new amino acid assignments, termination, and rapid freezing of the 22-acid code. Anticodons were recruited sequentially:
GNN, CNN, INN, and *UNN. CO2 fixation, photoreduction, and lipid synthesis probably evolved in the protocell before photophosphorylation. Signal recognition
particles, chaperones, compartmented proteases, and peptidoglycan arose prior to the last common ancestor of life, a complex
autotrophic, anaerobic green bacterium.
Received: 19 February 2001 / Accepted: 9 April 2001 相似文献
8.
The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon–anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of non-Watson–Crick pairs in the codon–anticodon helix and the interactions with bases of rRNA at the A-site decoding site. We derive a more information-rich, alternative representation of the genetic code, that is circular with an unsymmetrical distribution of codons leading to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. All tRNA sequence variations can be visualized, within an internal structural and energy framework, for each organism, and each anticodon of the sense codons. The multiplicity and complexity of nucleotide modifications at positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate well with the necessity to stabilize AU-rich codon–anticodon pairs and to avoid miscoding in split codon boxes. The evolution and expansion of the genetic code is viewed as being originally based on GC content with progressive introduction of A/U together with tRNA modifications. The representation we present should help the engineering of the genetic code to include non-natural amino acids. 相似文献
9.
The genetic code might be a historical accident that was fixed in the last common ancestor of modern organisms. 'Adaptive', 'historical' and 'chemical' arguments, however, challenge such a 'frozen accident' model. These arguments propose that the current code is somehow optimal, reflects the expansion of a more primitive code to include more amino acids, or is a consequence of direct chemical interactions between RNA and amino acids, respectively. Such models are not mutually exclusive, however. They can be reconciled by an evolutionary model whereby stereochemical interactions shaped the initial code, which subsequently expanded through biosynthetic modification of encoded amino acids and, finally, was optimized through codon reassignment. Alternatively, all three forces might have acted in concert to assign the 20 'natural' amino acids to their present positions in the genetic code. 相似文献
10.
Harry Buhrman Peter T. S. van der Gulik Gunnar W. Klau Christian Schaffner Dave Speijer Leen Stougie 《Journal of molecular evolution》2013,77(4):170-184
The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the mean square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By comparing this value with a distribution of values belonging to codes generated by random permutations of amino acid assignments, the level of error robustness of a genetic code can be quantified. We present a calculation in which the standard genetic code is shown to be optimal. We obtain this result by (1) using recently updated values of polar requirement as input; (2) fixing seven assignments (Ile, Trp, His, Phe, Tyr, Arg, and Leu) based on aptamer considerations; and (3) using known biosynthetic relations of the 20 amino acids. This last point is reflected in an approach of subdivision (restricting the random reallocation of assignments to amino acid subgroups, the set of 20 being divided in four such subgroups). The three approaches to explain robustness of the code (specific selection for robustness, amino acid–RNA interactions leading to assignments, or a slow growth process of assignment patterns) are reexamined in light of our findings. We offer a comprehensive hypothesis, stressing the importance of biosynthetic relations, with the code evolving from an early stage with just glycine and alanine, via intermediate stages, towards 64 codons carrying todays meaning. 相似文献
11.
If the genetic code arose in an RNA world, present codon assignments may reflect primordial RNA-amino acid affinities. Whether aptamers selected from random pools to bind free amino acids do so using the cognate codons at their binding sites has been controversial. Here we defend and extend our previous analysis of arginine binding sites, and propose a model for the maintenance of codon-amino acid interactions through the evolution of amino acids from ribozyme cofactors into the building blocks of proteins. 相似文献
12.
人类活动造成大气二氧化碳(CO2)浓度不断升高,使当今世界面临着气候变化的重大危机。微生物CO2固定为实现地球“碳中和”提供了一条有前景的绿色发展路线。与自养微生物相比,异养微生物具有更快的生长速度和更先进的遗传工具,但是其固定CO2的能力还很有限。近年来,基于合成生物学技术强化异养微生物CO2固定受到诸多关注,主要包括优化能量供给、改造羧化途径以及基于异养微生物间接固定CO2。本综述将围绕上述3个方面重点讨论异养微生物CO2固定的研究进展,为将来更好地利用微生物CO2固定技术实现“碳达峰、碳中和”提供参考。 相似文献
13.
The aminoacylation of tRNAs by the aminoacyl-tRNA synthetases recapitulates the genetic code by dictating the association between amino acids and tRNA anticodons. The sequences of tRNAs were analyzed to investigate the nature of primordial recognition systems and to make inferences about the evolution of tRNA gene sequences and the evolution of the genetic code. Evidence is presented that primordial synthetases recognized acceptor stem nucleotides prior to the establishment of the three major phylogenetic lineages. However, acceptor stem sequences probably did not achieve a level of sequence diversity sufficient to faithfully specify the anticodon assignments of all 20 amino acids. This putative bottleneck in the evolution of the genetic code may have been alleviated by the advent of anticodon recognition. A phylogenetic analysis of tRNA gene sequences from the deep Archaea revealed groups that are united by sequence motifs which are located within a region of the tRNA that is involved in determining its tertiary structure. An association between the third anticodon nucleotide (N36) and these sequence motifs suggests that a tRNA-like structure existed close to the time that amino acid-anticodon assignments were being established. The sequence analysis also revealed that tRNA genes may evolve by anticodon mutations that recruit tRNAs from one isoaccepting group to another. Thus tRNA gene evolution may not always be monophyletic with respect to each isoaccepting group.Based on a presentation made at a workshop— Aminoacyl-tRNA Synthetases and the Evolution of the Genetic Code—held at Berkeley, CA, July 17–20, 1994
Correspondence to: M.E. Saks 相似文献
14.
The origin of the genetic code is a central open problem regarding the early evolution of life. Here, we consider two undeveloped but important aspects of possible scenarios for the evolutionary pathway of the translation machinery: the role of unassigned codons in early stages of the code and the incorporation of tRNA anticodon modifications. As the first codons started to encode amino acids, the translation machinery likely was faced with a large number of unassigned codons. Current molecular scenarios for the evolution of the code usually assume the very rapid assignment of all codons before all 20 amino acids became encoded. We show that the phenomenon of nonsense suppression as observed in current organisms allows for a scenario in which many unassigned codons persisted throughout most of the evolutionary development of the code. In addition, we demonstrate that incorporation of anticodon modifications at a late stage is feasible. The wobble rules allow a set of 20 tRNAs fully lacking anticodon modifications to encode all 20 canonical amino acids. These observations have implications for the biochemical plausibility of early stages in the evolution of the genetic code predating tRNA anticodon modifications and allow for effective translation by a relatively small and simple early tRNA set. 相似文献
15.
G. Corduan 《Planta》1970,91(4):291-301
Summary It is possible to obtain autotrophic callus cultures by inhibiting cell respiration. During a first passage of four weeks the cultures synthesized chlorophyll on an agar-medium with a minimum of organic substances such as sugar, amino acids and vitamins. In the second passage these cultures were kept on the same medium but were aerated with a mixture of 99% N2 and 1% CO2. In the third and last passage the medium contained only mineral substances and the same mixture of N2 and CO2 was used for aeration. This pure mineral medium was supplemented with the Hoagland's solution.These autotrophic callus cultures were grown for about two years under these conditions and showed a growth quotient of ten.Three different groups of tissues were taken for the 14CO2-fixation. The first group was grown for four weeks on a heterotrophic medium and aerated with O2. This is the socalled respirating group. The second and third group were both aerated with the mixture of N2/CO2 but they were grown on different mediums. One of these groups was grown on a heterotrophic medium for four weeks: these are heterotrophic photosynthesizing tissues. The third group was grown on a pure mineral medium, and these are the autotrophic photosynthesizing callus tissues.Respirating tissues are different from photosynthesizing cultures in respect to the quantity of light-induced CO2-fixation.The thin-layer chromatograms reveal the difference between heterotrophic and autotrophic tissues. In the light dependent 14CO2-incorporation the difference is in the amounts of the labelled amino acids glycine and serine. In the dark dependent incorporation the difference is found in the amount of the labelled amino acid aspartic acid. The more autotrophic these tissues are, the higher the level of the CO2-fixation in these amino acids is.
Mit Hilfe der Deutschen Forschungsgemeinschaft. 相似文献
Mit Hilfe der Deutschen Forschungsgemeinschaft. 相似文献
16.
To explore how chemical structures of both nucleobases and amino acids may have played a role in shaping the genetic code,
numbers of sp2 hybrid nitrogen atoms in nucleobases were taken as a determinative measure for empirical stereo-electronic property to analyze
the genetic code. Results revealed that amino acid hydropathy correlates strongly with the sp2 nitrogen atom numbers in nucleobases rather than with the overall electronic property such as redox potentials of the bases,
reflecting that stereo-electronic property of bases may play a role. In the rearranged code, five simple but stereo-structurally
distinctive amino acids (Gly, Pro, Val, Thr and Ala) and their codon quartets form a crossed intersection “core”. Secondly,
a re-categorization of the amino acids according to their β-carbon stereochemistry, verified by charge density (at β-carbon)
calculation, results in five groups of stereo-structurally distinctive amino acids, the group leaders of which are Gly, Pro,
Val, Thr and Ala, remarkably overlapping the above “core”. These two lines of independent observations provide empirical arguments
for a contention that a seemingly “frozen” “core” could have formed at a certain evolutionary stage. The possible existence
of this codon “core” is in conformity with a previous evolutionary model whereby stereochemical interactions may have shaped
the code. Moreover, the genetic code listed in UCGA succession together with this codon “core” has recently facilitated an
identification of the unprecedented icosikaioctagon symmetry and bi-pyramidal nature of the genetic code. 相似文献
17.
Akio Kawahara-Kobayashi Akiko Masuda Yuhei Araiso Yoko Sakai Atsushi Kohda Masahiko Uchiyama Shun Asami Takayoshi Matsuda Ryuichiro Ishitani Naoshi Dohmae Shigeyuki Yokoyama Takanori Kigawa Osamu Nureki Daisuke Kiga 《Nucleic acids research》2012,40(20):10576-10584
At earlier stages in the evolution of the universal genetic code, fewer than 20 amino acids were considered to be used. Although this notion is supported by a wide range of data, the actual existence and function of the genetic codes with a limited set of canonical amino acids have not been addressed experimentally, in contrast to the successful development of the expanded codes. Here, we constructed artificial genetic codes involving a reduced alphabet. In one of the codes, a tRNAAla variant with the Trp anticodon reassigns alanine to an unassigned UGG codon in the Escherichia coli S30 cell-free translation system lacking tryptophan. We confirmed that the efficiency and accuracy of protein synthesis by this Trp-lacking code were comparable to those by the universal genetic code, by an amino acid composition analysis, green fluorescent protein fluorescence measurements and the crystal structure determination. We also showed that another code, in which UGU/UGC codons are assigned to Ser, synthesizes an active enzyme. This method will provide not only new insights into primordial genetic codes, but also an essential protein engineering tool for the assessment of the early stages of protein evolution and for the improvement of pharmaceuticals. 相似文献
18.
Wei Wan Jeffery M. TharpWenshe R. Liu 《Biochimica et Biophysica Acta - Proteins and Proteomics》2014,1844(6):1059-1070
The genetic incorporation of the 22nd proteinogenic amino acid, pyrrolysine (Pyl) at amber codon is achieved by the action of pyrrolysyl-tRNA synthetase (PylRS) together with its cognate tRNAPyl. Unlike most aminoacyl-tRNA synthetases, PylRS displays high substrate side chain promiscuity, low selectivity toward its substrate α-amine, and low selectivity toward the anticodon of tRNAPyl. These unique but ordinary features of PylRS as an aminoacyl-tRNA synthetase allow the Pyl incorporation machinery to be easily engineered for the genetic incorporation of more than 100 non-canonical amino acids (NCAAs) or α-hydroxy acids into proteins at amber codon and the reassignment of other codons such as ochre UAA, opal UGA, and four-base AGGA codons to code NCAAs. 相似文献
19.
Gerhard Melcher 《Radiation and environmental biophysics》1970,7(1):25-28
Summary Starting from the assumption that specific steric and energetic interactions between amino acids and their respective anticodons could exist, the evolution of the genetic code is deduced from purely chemical and physical reasons. In this model the amino acids are intercalated between the two first anticodon bases and their carbon bound hydrogen atoms are assumed to penetrate into the electron clouds of the bases. By these means a gain in energy and a fixation of the amino acid is obtained in such a way that the anticodon nucleotides could be determinant for the nature of the amino acids. 相似文献
20.
Since the genetic code first was determined, many have claimed that it is organized adaptively, so as to assign similar codons
to similar amino acids. This claim has proved difficult to establish due to the absence of relevant comparative data on alternative
primordial codes and of objective measures of amino acid exchangeability. Here we use a recently developed measure of exchangeability
to evaluate a null hypothesis and two alternative hypotheses about the adaptiveness of the genetic code. The null hypothesis
that there is no tendency for exchangeable amino acids to be assigned to similar codons can be excluded here as expected from
earlier work. The first alternative hypothesis is that any such correlation between codon distance and amino acid distance
is due to incremental mechanisms of code evolution, and not to adaptation to reduce deleterious effects of future mutations.
More specifically, new codon assignments that occur by ambiguity reduction or by codon capture will tend to give rise to correlations,
whether due to the condition of amino acid ambiguity, or to the condition of similarity between a new tRNA synthetase (or
tRNA) and its parent. The second alternative hypothesis, the adaptive hypothesis, then may be defined as an excess relative
to what may be expected given the incremental nature of evolution, reflecting true adaptation for robustness rather than an
incidental effect. The results reported here indicate that most of the nonrandomness in the amino acids to codon assignments
can be explained by incremental code evolution, with a small residue of orderliness that may reflect code adaptation. 相似文献