Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genetic code”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1968

Life's irreducible structure. Live mechanisms and information in DNA are boundary conditions with a sequence of boundaries above them.

Mechanisms, whether man-made or morphological, are boundary conditions harnessing the laws of inanimate nature, being themselves irreducible to those laws. The pattern of organic bases in DNA which functions as a genetic code is a boundary condition irreducible to physics and chemistry. Further controlling principles of life may be represented as a hierarchy of boundary conditions extending, in the case of man, to consciousness and responsibility.

Biological Evolution↗
PubMed2006

Intramolecular interactions in aminoacyl cyclic-3',5'-nucleotides.

Polymerization of amino-acid acyl cyclic-3',5'-nucleotides is postulated to be the origin of RNA and associated protein in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleotide base and the amino-acid side chain determines the stability of the particular complex, resulting in a preferred association (or coding) of a base for a particular amino acid. The compounds studied were glycine acyl cyclic-3',5'-guanylate where the strong hydrogen bond between protonated glycine and guanine N7 gives an enthalpy change of -0.05 h. Similarly, hydrogen bonds in l-lysine acyl cyclic-3',5'-adenylate give an enthalpy change of -0.06 h. Hydrophobic interactions in l-phenylalanine acyl cyclic-3',5'-uridylate give an enthalpy change of -0.02 h and the corresponding value for l-proline acyl cyclic-3',5'-cytidylate is -0.01 h. These interactions were expected to be modified as the genetic code became a duplet and finally a triplet code. The interactions have been shown to be feasible from the overall enthalpy changes in the ZKE approximation at the MP2/6-31G* level.

Amino Acids↗
PubMed1984

The development of biochemistry in the 20th century.

This lecture consists of a short appraisal of some of the main features that have characterized the growth of biochemistry during the course of the 20th century. It dwells on the early impacts of vitalism, the emergence and elucidation of the vitamins, the discovery of coenzymes, the concept of active centres of enzymes, the development of experimental techniques (including the use of isotopes), the genetic code, and on the development of molecular biology and closely allied fields of investigation. It concludes with a consideration of the influence of the study of membranes and of neurochemistry on current biochemical thought.

Animals↗
PubMed1980

In vitro suppression of UGA codons in a mitochondrial mRNA.

Although both prokaryotic and eukaryotic messenger RNAs can be easily translated in heterologous protein-synthesizing systems, attempts to achieve correct synthesis of mitochondrial proteins by translation of mitochondrial mRNAs in such systems have failed. In general, the products of synthesis are of low molecular weight and presumably represent fragments of mitochondrial proteins. These fragments display a strong tendency to aggregate. Explanations have included the use by mitochondria of codons requiring a specialized tRNA population and the fortuitous occurrence within genes of purine-rich sequences resembling bacterial ribosome binding sites. In addition, the long 5'-leader sequences present in many mitochondrial (mt) RNAs may also contribute to difficulties in mRNA recognition by heterologous ribosomes. Recent sequence analysis of human mtDNA suggests that the genetic code used by mammalian mitochondria deviates in a number of respects from the 'universal' code, the most striking of these being the use of the UGA termination codon to specify tryptophan. That this may also apply in yeast mitochondria has been shown by Fox and Macino et al., thus providing an obvious and easily testable explanation for the inability of heterologous systems to synthesize full-length mitochondrial proteins. We confirm this explanation and describe here the in vitro synthesis of a full-length subunit II of yeast cytochrome c oxidase in a wheat-germ extract supplemented with a partially purified mitochondrial mRNA for this protein and a UGA-suppressor tRNA from Schizosaccharomyces pombe.

Codon↗
PubMed1986

Nucleotide sequence of the Paramecium primaurelia G surface protein. A huge protein with a highly periodic structure.

The complete DNA sequence of the G surface protein of Paramecium primaurelia has been determined. It contains an open reading frame of 8145 nucleotides devoid of introns and coding for a protein of 329,000 Mr. Analysis of the deduced amino acid sequence reveals remarkable features such as important internal homologies and a periodic structure, which could be dictated in part by the rigid scaffolding of cysteine residues. The predicted secondary structure shows a quasi absence of alpha-helix and an abundance of beta-pleated sheets and random coils. The monotony of the amino acid sequence is in favour of a structural role for the protein. Interestingly, homologies with other proteins are limited to surface antigens of trypanosomes. Finally, our data are consistent with a genetic code for paramecium which differs from the "universal" code by the assignment of TAA and TAG codons to glutamine.

Amino Acid Sequence↗
PubMed1995

On codon reassignment.

Schultz and Yarus (J. Mol. Biol. 235:1377-1380, 1994) have proposed that reassignment of codons in the genetic code passes through a stage in which the codons are ambiguously translated. In contrast we state that such ambiguity would be deleterious, and that, to be reassigned, a codon, together with the tRNA that translates the codon, must first disappear from coding sequences, after which a tRNA appears with a mutated anticodon, and this enables the codon to reappear with a changed meaning. In the case of a stop codon, the relevant release factor must change so as to recognize it.

Codon↗
PubMed1985

Conformational relationships between amino acids and their anticodons in the primitive decoding system.

Detailed calculations of the conformational characteristics of a primitive decoding system are presented. A penta-nucleotide serves as the primitive tRNA (PIT) with a triplet of primitive anticodon (PAC) in a helical conformation. This molecular moiety has a cleft in the middle. An amino acid can comfortably nestle into the cleft. The conformation of this molecular association is stabilised by a few hydrogen bonds. The stereochemistry of the moiety restricts the conformational possibilities and the sidechain of the amino acid gets oriented at a proper position and in the correct direction to interact intimately with the PAC in the middle of the PIT. The model favours L-amino acids for beta-D-ribonucleotides. The location of the sidechain of the amino acid in the PIT gives a raison d'être for the important features of the organisation of nucleotide triplets for amino acids in the Genetic Code. The interaction of a few key amino acids with the different combinations of bases as PAC sequences has been studied and the stereochemical basis for the selection of the anticodons for amino acids is elucidated.

Amino Acids↗
PubMed1974

Translational reinitiation: reinitiation of lac repressor fragments at three internal sites early in the lac i gene of Escherichia coli.

Three early amber mutations in the lac i gene have been shown to arise from the codons corresponding to residues 7, 12, and 17 of the lac repressor polypeptide chain. All three mutations allow translational reinitiation at the same two sites, resulting in the synthesis of two lac repressor fragments. The amino-terminal sequences of these fragments show that the first site is the triplet coding for valine residue 23, while the second is the first internal in-phase AUG codon corresponding to residue 42. Translational reinitiation appears to be a common event in E. coli, since there are at least three such sites in the first 70 in-phase codons of the i-gene messenger RNA, and all amber mutants found in this region show translational reinitiation. Only one of these sites involves an AUG codon; the other two involve an in vivo ambiguity of the genetic code, in that the same codon can be translated into two different amino acids depending on whether it is recognized during initiation or elongation of protein biosynthesis. The two non-AUG codons are the codons corresponding to leucine residue 62 and valine residue 23 of the lac repressor.

Amino Acid Sequence↗
PubMed2006

Distinct paths to stop codon reassignment by the variant-code organisms Tetrahymena and Euplotes.

The reassignment of stop codons is common among many ciliate species. For example, Tetrahymena species recognize only UGA as a stop codon, while Euplotes species recognize only UAA and UAG as stop codons. Recent studies have shown that domain 1 of the translation termination factor eRF1 mediates stop codon recognition. While it is commonly assumed that changes in domain 1 of ciliate eRF1s are responsible for altered stop codon recognition, this has never been demonstrated in vivo. To carry out such an analysis, we made hybrid proteins that contained eRF1 domain 1 from either Tetrahymena thermophila or Euplotes octocarinatus fused to eRF1 domains 2 and 3 from Saccharomyces cerevisiae. We found that the Tetrahymena hybrid eRF1 efficiently terminated at all three stop codons when expressed in yeast cells, indicating that domain 1 is not the sole determinant of stop codon recognition in Tetrahymena species. In contrast, the Euplotes hybrid facilitated efficient translation termination at UAA and UAG codons but not at the UGA codon. Together, these results indicate that while domain 1 facilitates stop codon recognition, other factors can influence this process. Our findings also indicate that these two ciliate species used distinct approaches to diverge from the universal genetic code.

Animals↗
PubMed1967

The chemical production of mutations. The effect of chemical mutagens on cells and their genetic material is discussed.

Since the discovery of the first potent mutagens over 20 years ago, progress in mutation research has been rapid. Many new mutagens, belonging to a variety of chemical classes, have been discovered, and for some of them the reaction with DNA in vitro has been established. It seems that the findings of these chemical investigations usually also apply to viruses which are treated outside the cell. This has made chemical mutagens into an important tool for the analysis of the genetic code. When DNA is treated inside the cell, its reactions would not be expected to be always identical with those observed in vitro; in one case they have, indeed, been found to be different.

Acridines↗
PubMed1987

Physiological levels of normal tRNA(CAGGln) can effect partial suppression of amber mutations in the yeast Saccharomyces cerevisiae.

A number of ciliated protozoa are known to read the stop codons UAA and UAG as sense codons that specify glutamine during protein synthesis. In considering evolutionary mechanisms for this curious divergence from the standard genetic code, we propose the existence of progenitor tRNAs for glutamine that can weakly suppress UAA and UAG codons. It has been previously shown that multicopy plasmids that overexpress normal tRNA(CAAGln) and tRNA(CAGGln) genes from the yeast Saccharomyces cerevisiae can partially suppress a number of yeast ochre and amber mutations, respectively. In the present study we show that the tRNA(CAGGln) gene can also function as a weak amber suppressor when expressed in cells at physiological levels. This observation is consistent with a role of tRNA(CAGGln) as an evolutionary progenitor of tRNAs that strongly decode UAG codons.

Animals↗
PubMed1992

The mitochondrial genomes of two nematodes, Caenorhabditis elegans and Ascaris suum.

The nucleotide sequences of the mitochondrial DNA (mtDNA) molecules of two nematodes, Caenorhabditis elegans [13,794 nucleotide pairs (ntp)], and Ascaris suum (14,284 ntp) are presented and compared. Each molecule contains the genes for two ribosomal RNAs (s-rRNA and l-rRNA), 22 transfer RNAs (tRNAs) and 12 proteins, all of which are transcribed in the same direction. The protein genes are the same as 12 of the 13 protein genes found in other metazoan mtDNAs: Cyt b, cytochrome b; COI-III, cytochrome c oxidase subunits I-III; ATPase6, Fo ATPase subunit 6; ND1-6 and 4L, NADH dehydrogenase subunits 1-6 and 4L: a gene for ATPase subunit 8, common to other metazoan mtDNAs, has not been identified in nematode mtDNAs. The C. elegans and A. suum mtDNA molecules both include an apparently noncoding sequence that contains runs of AT dinucleotides, and direct and inverted repeats (the AT region: 466 and 886 ntp, respectively). A second, apparently noncoding sequence in the C. elegans and A. suum mtDNA molecules (109 and 117 ntp, respectively) includes a single, hairpin-forming structure. There are only 38 and 89 other intergenic nucleotides in the C. elegans and A. suum mtDNAs, and no introns. Gene arrangements are identical in the C. elegans and A. suum mtDNA molecules except that the AT regions have different relative locations. However, the arrangement of genes in the two nematode mtDNAs differs extensively from gene arrangements in all other sequenced metazoan mtDNAs. Unusual features regarding nematode mitochondrial tRNA genes and mitochondrial protein gene initiation codons, previously described by us, are reviewed. In the C. elegans and A. suum mt-genetic codes, AGA and AGG specify serine, TGA specifies tryptophan and ATA specifies methionine. From considerations of amino acid and nucleotide sequence similarities it appears likely that the C. elegans and A. suum ancestral lines diverged close to the time of divergence of the cow and human ancestral lines, about 80 million years ago.

Amino Acid Sequence↗
PubMed2000

Ribozyme-catalyzed tRNA aminoacylation.

The RNA world hypothesis implies that coded protein synthesis evolved from a set of ribozyme catalyzed acyl-transfer reactions, including those of aminoacyl-tRNA synthetase ribozymes. We report here that a bifunctional ribozyme generated by directed in vitro evolution can specifically recognize an activated glutaminyl ester and aminoacylate a targeted tRNA, via a covalent aminoacyl-ribozyme intermediate. The ribozyme consists of two distinct catalytic domains; one domain recognizes the glutamine substrate and self-aminoacylates its own 5'-hydroxyl group, and the other recognizes the tRNA and transfers the aminoacyl group to the 3'-end. The interaction of these domains results in a unique pseudoknotted structure, and the ribozyme requires a change in conformation to perform the sequential aminoacylation reactions. Our result supports the idea that aminoacyl-tRNA synthetase ribozymes could have played a key role in the evolution of the genetic code and RNA-directed translation.

Acylation↗
PubMed1984

Sequence and arrangement of the genes for cytochrome b, URF1, URF4L, URF4, URF5, URF6 and five tRNAs in Drosophila mitochondrial DNA.

The nucleotide sequence of a segment of the mtDNA molecule of Drosophila yakuba has been determined, within which have been identified the 3' end of the large rRNA gene and the entire genes for tRNAleuCUN , URF1 , tRNAserUCN , cytochrome b, URF6 , tRNApro, tRNAthr , URF4L , URF4 , tRNAhis and URF5 . The genes are arranged in the order given, with the large rRNA gene being closest to the A+T-rich region which contains the origin of replication. Transcription of all of these genes except those for cytochrome b, URF6 , tRNAserUCN and tRNAthr proceeds in the same direction as replication. Differences occur in the relative arrangement and in the direction of transcription of these twelve genes between D. yakuba and mammalian mtDNA molecules. Internal AGA codons occur in all of the polypeptide genes except URF6 . Comparisons of the positions of these AGA codons to codons in corresponding mouse genes is consistent with the view that in the D. yakuba mitochondrial genetic code AGA specifies serine. Genes equivalent to all of the polypeptide, tRNA and rRNA genes found in mammalian mtDNA have now been identified in D. yakuba mtDNA.

Amino Acid Sequence↗
PubMed1977

Structural convergence during protein evolution.

Several recent protein crystallographic structure determinations have demonstrated the existence of considerable tertiary structural similarity among proteins otherwise having little similarity in either amino acid sequence or biological function. In order to assess the possibility that such proteins may have arisen through processes of divergent evolution from a common ancestor, a graphical presentation is given which correlates the pattern of allowed single base substitutions defined by the genetic code with the associated changes in the structural properties of the encoded amino acids. The results show that while a large degree of structural conservation is evident due to codon synonomy, there is, in general, little tendency for the code to be structurally conservative in the majority of the cases where codon single-base changes result in amino acid substitutions. The possible consequences of this pattern of potential amino acid substitutions are discussed in relation to protein evolutionary processes.

Amino Acids↗
PubMed1966

Problems in protein biosynthesis.

Outline of the steps in protein synthesis. Nature of the genetic code. The use of synthetic oligo- and polynucleotides in deciphering the code. Structure of the code: relatedness of synonym codons. The wobble hypothesis. Chain initiation and N-formyl-methionine. Chain termination and nonsense codons. Mistakes in translation: ambiguity in vitro. Suppressor mutations resulting in ambiguity. Limitations in the universality of the code. Attempts to determine the particular codons used by a species. Mechanisms of suppression, caused by (a) abnormal aminoacyl-tRNA, (b) ribosomal malfunction. Effect of streptomycin. The problem of "reading" a nucleic acid template. Different ribosomal mutants and DNA polymerase mutants might cause different mistakes. The possibility of involvement of allosteric proteins in template reading.

Genetic Code↗
PubMed1983

Codon-level analysis of histone primary sequence: evidence of a repeat tetrapeptide origin and later inclusion of transcribed sequence.

This work is directed to the question of protein sequence conservation. By reference to the genetic code the aminoacyl sequence of histones H2A, H4, H3, H2B and H1 (fragment) were rewritten as the codon sequences. The N-terminal regions were set aside on the grounds of different composition and sequence. The remainder of the molecule could be referred to simple repeat-tetrapeptide proteins by codon composition (high Gxy, low xGy content) and by sequence. Random segments of three to six residues occur characterized by composition and sequence as originating from the complimentary DNA strand, i.e. as codon "transcript". Ancestral features are probably best seen in H3, point mutations appear to be more extensive in H2B and H1. Segments in reverse order in H2A and in "transcript" in H4 distinguish these two from the other three histones. There is a tenuous possibility the N-terminals also originated as repeat-tetrapeptide now intensively modified. At codon-level the 50S ribosomal protein (L7/L12) of E. coli has features in common with histones (including a palindrome-containing N-terminal). It has the composition and sequence of a well-conserved tetrapeptide-repeat strand (statistical support). If interpretations made here are substantially correct, the 50S r-protein illustrates a significant stage in evolution of histone codon strands.

Amino Acid Sequence↗
PubMed1975

Beta structures of alternating polypeptides and their possible prebiotic significance.

A survey of the commonest amino acids formed in prebiotic conditions suggests that the earliest form of genetic coding may have specified polypeptides with a strong tendency to form stable Beta-sheet structure. Poly(Val-Lys), like other polypeptides in which hydrophobic and hydrophilic residues alternate, tends to form Beta structures. We show that bilayers with a hydrophobic interior and a hydrophilic exterior may be present in aqueous solution.

Chemical Phenomena↗