Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Codons”

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 307 records · Page 17Linked to original sources
PubMed1989

Codon contexts from weakly expressed genes reduce expression in vivo.

Nucleotides that neighbor codons in Escherichia coli genes are highly non-random. Furthermore, these context biases are stronger and extend farther from the codon in weakly expressed than in highly expressed genes. We therefore suggested that codon contexts are selected to reduce gene expression levels. We now compare the expression levels of lacZ genes containing two specific coding sequences (context inserts). One context insert represents contexts seen in weakly expressed genes (low variant); the other represents contexts seen in highly expressed genes (high variant). The two variants have identical nucleotide and codon compositions, and encode the same protein. A permutation of four nucleotides, which changes eight codon:codon interfaces of 1043, comprises the only difference between the high and low context variant genes. In three different lacZ mRNAs, the low variant was expressed at a level significantly below that of the high variant. This context effect depends entirely on translation of the contexts in the correct frame; its magnitude depends in part on the placement of other features (e.g. transcriptional pauses and terminators, or perhaps other slow codons or contexts) in the mRNAs. Changing the ribosome density on the message by changing the ribosome binding site distinguishes between dropoff, interference and polarity, three fundamentally different types of models for the context effect. The expression difference between context variants is eliminated by both increases and decreases in the ribosome initiation frequency, as uniquely predicted by the polarity model. In fact, data from all constructions are accommodated by a model in which slow translation of the low context insert increases rho-dependent transcriptional termination within the test gene. The data suggest that the rates of translational initiation and elongation are poised with respect to the rate of transcriptional elongation so that all are influential in setting the expression level of wild-type lacZ. We conclude that context-induced polarity will exist in genes wherever low and reproducible gene product levels have been selected.

Amino Acid Sequence↗
PubMed1989

Codon recognition patterns as deduced from sequences of the complete set of transfer RNA species in Mycoplasma capricolum. Resemblance to mitochondria.

The nucleotide sequences of the complete set of tRNA species in Mycoplasma capricolum, a derivative of Gram-positive eubacteria, have been determined. This bacterium represents the first genetic system in which the sequences of all the tRNA species have been determined at the RNA level. There are 29 tRNA species: three for Leu, two each for Arg, Ile, Lys, Met, Ser, Thr and Trp, and one each for the other 12 amino acids as judged from aminoacylation and the anticodon nucleotide sequences. The number of tRNA species is the smallest among all known genetic systems except for mitochondria. The tRNA anticodon sequences have revealed several features characteristic of M. capricolum. (1) There is only one tRNA species each for Ala, Gly, Leu, Pro, Ser and Val family boxes (4-codon boxes), and these tRNAs all have an unmodified U residue at the first position of the anticodon. (2) There are two tRNAThr species having anticodons UGU and AGU; the first positions of these anticodons are unmodified. (3) There is only one tRNA with anticodon ICG in the Arg family box (CGN); this tRNA can translate codons CGU, CGC and CGA. No tRNA capable of translating codon CGG has been detected, suggesting that CGG is an unassigned codon in this bacterium. (4) A tRNATrp with anticodon UCA is present, and reads codon UGA as Trp. On the basis of these and other observations, novel codon recognition patterns in M. capricolum are proposed. A comparatively small total, 13, of modified nucleosides is contained in all M. capricolum tRNAs. The 5' end nucleoside of the T psi C-loop (position 54) of all tRNAs is uridine, not modified to ribothymidine. The anticodon composition, and hence codon recognition patterns, of M. capricolum tRNAs resemble those of mitochondrial tRNAs.

Amino Acids↗
PubMed1991

tRNA anticodons with the modified nucleoside 2-methylthio-N6-(4-hydroxyisopentenyl)adenosine distinguish between bases 3' of the codon.

The modified nucleoside 2-methylthio-N6-(4-hydroxyisopentenyl)adenosine (ms2io6A) is present immediately to the 3' side of the anticodon (position 37) in tRNAs that read codons starting with uridine and hence include amber (UAG) suppressor tRNAs. We have used strains of Salmonella typhimurium that differ only in their ability to synthesize ms2io6A in order to determine specifically how this modified nucleoside influences the efficiency of amber suppression in two codon contexts differing by only which base is 3' of the codon. The results show that the presence of the modified nucleoside ms2io6A not only improves the efficiency of the suppressor tRNAs but also allows them to distinguish between at least two bases 3' of the codon. Thus, the presence of ms2io6A reduces the intrinsic codon context sensitivity of the tRNA and specifically counteracts an unfavourable nucleotide on the 3' side of the codon. The possible codon-anticodon interactions responsible for this effect are discussed.

Anticodon↗
PubMed1992

Both forms of translational initiation factor IF2 (alpha and beta) are required for maximal growth of Escherichia coli. Evidence for two translational initiation codons for IF2 beta.

The gene infB codes for two forms of translational initiation factor IF2; IF2 alpha (97,300 Da) and IF2 beta (79,700 Da). IF2 beta arises from an independent translational event on a GUG codon located 471 bases downstream from IF2 alpha start codon. By site-directed mutagenesis we constructed six different mutations of this GUG codon. In all cases, IF2 beta synthesis was variably affected by the mutations but not abolished. We show that the residual expression of IF2 beta results from translational initiation on an AUG codon located 21 bases downstream from the mutated GUG. Furthermore, two forms of IF2 beta have been separated by fast protein liquid chromatography and the determination of their N-terminal sequences indicated that they resulted from two internal initiation events, one occurring on the previously identified GUG start codon, the other on the AUG codon immediately downstream. We conclude that two forms of IF2 beta exist in the cell, which differ by seven aminoacid residues at their N terminus. Only by mutating both IF2 beta start codons could we construct plasmids that express only IF2 alpha. A plasmid expressing only IF2 beta was obtained by deletion of the proximal region of the infB gene. Using a strain that carries a null mutation in the chromosomal copy of infB and a functional copy of the same gene on a thermosensitive lysogenic lambda phage, we could cure the lambda phage when the plasmids expressing only one form of IF2 were supplied in trans. We found that each one of the two forms of IF2, at near physiological levels, can support growth of Escherichia coli, but that growth is retarded at 37 degrees C. This result shows that both forms of IF2 are required for maximal growth of the cell and suggests that they have acquired some specialized but not essential function.

Amino Acid Sequence↗
PubMed1992

Replication capacities of natural and artificial precore stop codon mutants of hepatitis B virus: relevance of pregenome encapsidation signal.

The emergence of hepatitis B virus variants unable to express HBe protein during late stage of viral infection may represent an important mechanism of viral persistence. The molecular mechanisms responsible for the elimination of HBe expression are nonsense or frameshift mutations or initiation codon mutations in part of its coding sequence, the precore region. So far only 2 of the 29 precore amino acid codons have been found mutated to stop codons in nature, although a total of 10 codons are convertible to stop codons by single nucleotide changes. Since the HBe-coding sequence is largely overlapped by the pregenome encapsidation signal (epsilon signal), a recently found cis-acting element required for the packaging of pregenomic RNA, the absence of other potential nonsense mutants could result from their impairment of the epsilon signal. Seven such potential stop codon mutants were constructed and tested for replication capacities by transfection into a hepatoma cell line. Five mutants were replication competent, but at levels lower than that of a prevalent natural stop codon mutant. The remaining two mutants were completely defective in DNA replication, which clearly explained why these two mutants are not found in nature. Northern blot analysis revealed wild-type levels of RNA transcription by these two mutants but complete lack of packaged pregenomic RNA. Additional studies lent further support to the importance of the epsilon signal in pregenome encapsidation and suggested relaxed sequence requirements for the computer-predicted hexanucleotide bulge region as compared to the hexanucleotide loop of the signal.

Base Sequence↗
PubMed1982

Cell-type specific codon usage and differentiation.

This paper presents evidence derived from the selective use of codons in ca. 40 eukaryotic genes (or messages derived from them) that codon usage is one of the most conserved features of messages for specific cell products. The theory has been developed by several investigations that the kinds of products of many if not most kinds of differentiated cells is determined by the pattern of translation abilities each cell possesses as it differentiates. A correllary of this thesis is that the groups of code words used for products of specific cell types, INDEPENDENTLY OF THE SPECIES INVOLVED, should exclude specific kinds of code words in one cell type and not another. To test this thesis, the specific frequency of codon usage and non-usage has been collated from the recently published literature and subjected to appropriate computer analysis. We find that: (1) certain codons are not used at all in any message for globins; (2) the pattern of codon usage is characteristic of specific products from specific embryonic derivatives, e.g. erythrocytes; (3) that certain code words are discriminated against generally in nearly all vertebrate cell messages evaluated; and (4) that the cell type from which a message is derived can be identified, at least in the case of 9 globin messages derived from species separated by millions of generations, purely on the basis of codon usage. From these studies it can be inferred that some evolutionary factor prevents the use of "forbidden" code words in specific kinds of cells. We propose that this factor derives from the fact that a "silent" mutation to a code word which is untranslatable by a differentiated cell will be lethal in the homozygous condition and that the thesis that so-called "codon restriction" is an important determinative factor in limiting what differentiating cells can synthesize in many kinds of developing cells explains the available evidence more adequately than alternative theories.

Animals↗
PubMed1986

Multiple upstream AUG codons mediate translational control of GCN4.

GCN4 encodes a transcriptional activator of amino acid biosynthetic genes in yeast that is regulated at the translational level. The 5' leader of GCN4 mRNA contains four small open-reading-frames. By constructing point mutations in the initiation codons of these sequences, we show that they are essential for translational repression of GCN4. Each upstream AUG codon can repress translation; however, the two 3' proximal AUG codons are much more inhibitory than the 5' proximal AUG codons. Unexpectedly, the first AUG codon is required for efficient GCN4 expression under starvation conditions. This positive function appears to involve antagonism of the inhibitory effect of the 3' proximal AUG codons since it is dispensable in the absence of these sequences. The interaction between the upstream AUG codons is modulated by the trans-acting factors GCN2 and GCD1 in response to amino acid availability.

Amino Acids↗
PubMed1995

The ability of bovine mitochondrial transfer RNAMet to decode AUG and AUA codons.

The ability of bovine mitochondrial tRNA(Met) with the anticodon f5CAU (where f5C is 5-formylcytidine) to decode AUG and AUA codons was examined in a codon-dependent ribosomal binding assay. The AUG codon stimulated the binding of Met-tRNA(Met) to mitochondrial ribosomes in the presence of EF-Tu/TSmt. In contrast, the AUA codon did not promote the binding to mitochondrial Met-tRNA to the ribosome. To investigate the translation of the AUG and AUA codons more fully, an in vitro translation system from bovine liver mitochondria was developed. The activity of this system was greatly enhanced by the addition of 1 mM spermine and reached about half the activity observed with a comparable translational system from E coli. Two types of mRNA containing either AUG or AUA codons were synthesized using T7 RNA polymerase to transcribe their chemically synthesized genes. In the E coli system, the AUG-containing mRNA was translated as Met and the AUA-containing mRNA was translated as Ile. The AUG-containing mRNA but not the AUA-containing mRNA was translated as Met by the mitochondrial translational system. The process by which the AUA codon is translated as Met in the mitochondrial system remains to be clarified.

Animals↗
PubMed1992

A universal compositional correlation among codon positions.

We have investigated the compositional distributions of third codon positions of genes from the 16 prokaryotes and seven eukaryotes for which the largest numbers of coding sequences are available in data banks. In prokaryotes, both narrow and broad distributions were found. In eukaryotes, distributions were very broad (except for Saccharomyces cerevisiae) and remarkably different for different genomes. In low-GC genomes, third codon positions were lower in GC than first + second codon positions and trailed towards high GC; the opposite situation was found for high-GC genomes. In all genomes, first codon positions were higher in GC than second codon positions. We then investigated the compositional correlations between third and first + second codon positions in prokaryotic genomes (the 16 mentioned above plus 87 additional ones) and in genome compartments of eukaryotes. A general, common relationship was found, which also holds within the same (heterogeneous) genomes. This universal correlation is due to the fact that the relative effects of compositional constraints on different codon positions are the same, on the average, whatever the genome under consideration.

Animals↗
PubMed1993

Codon preference in corynebacteria.

The codon usage (CU) of 34 genes from the closely related species, Brevibacterium lactofermentum and Corynebacterium glutamicum (BLCG), was analysed and compared with that of 23 genes from other Brevibacterium and Corynebacterium species. The G+C content of the BLCG genes ranged from 50 to 62%. A wider range was found in other corynebacterial genes (25-71%). The G+C contents of non-coding regions in glutamic acid bacteria are lower than those of the coding regions and both values are lower than the G+C content of ribosomal RNA (rRNA) sequences, suggesting an unusual biased mutation pressure. The CU and synonymous codon usage (SCU) analysis showed several common characteristics among the sequenced corynebacterial genes, consistent with the close relatedness of B. lactofermentum and C. glutamicum. A subset of 25 preferred codons were deduced from the presumably highly expressed genes and they encode most of the amino acid (aa) residues of the BLCG group. An analysis of the effective number of codons (Nc) was carried out in order to check the GC3s (G+C content at the silent third position of sense codons) dependence of the CU in corynebacteria. Nc values showed differences between the BLCG group and other corynebacterial sequences. A comparison of the most used codons for each aa showed a stronger similarity to Streptomyces than to Escherichia coli. The CU/SCU tables of corynebacteria are useful for identification of protein-coding regions, including start codons when they are uncertain, and for designing oligodeoxyribonucleotide probes from an aa sequence.

Base Sequence↗
PubMed1998

The relationship between synonymous codon usage and protein structure.

The hypothesis that synonymous codon usage is related to protein three-dimensional structure is examined by investigating the correlation between synonymous codon usage and protein secondary structure. All except two codons in E. coli show the same secondary structural preference for alpha-helix, beta-strand or coil as that of amino acids to be encoded by the respective codons, while 17 codons show secondary structural bias in mammalian proteins. The results indicate that there is no significant correlation between synonymous codon usage and protein secondary structure in E. coli, but there is a correlation in mammals. It could be deduced that synonymous codons carry much less structural information in prokaryotes than in eukaryotes due to their divergent evolutionary mechanism.

Animals↗
PubMed1992

Codon usage in Entamoeba histolytica.

The codon usage of 10 E. histolytica genes comprising 4455 codons was analysed. The codon usage revealed an extremely biased use of synonymous codons with a preference for NNU (44%) and NNA (41.4%) codons. Codons CGG (arg), AGG (arg) and CCG (pro) were absent in the E. histolytica genes examined. The codon usage of E. histolytica resembled that of Plasmodium falciparum.

Animals↗
PubMed1998

The codon 55 polymorphism in the paraoxonase 1 gene is not associated with the risk of coronary heart disease in Asian Indians and Chinese.

Recently several but not all studies have implicated the codon 192 polymorphism in the paraoxonase 1 (PON1) gene with the risk of coronary heart disease (CHD). These findings suggest that this polymorphism is not functional but rather may be in linkage disequilibrium with a functional mutation in the PON1 or a nearby gene. In this investigation, we have evaluated the role of another common polymorphism in the PON1 gene at codon 55 with the risk of CHD in a biracial sample of Asian Indians and Chinese. We observed a significant inter-racial variability in the allelic distribution as the frequency of the less common allele, codon 55/L, was significantly higher in Indians than Chinese (0.202 versus 0.036; P < 0.0001). However, despite this inter-racial difference the codon 55 polymorphism was neither associated with CHD risk nor with plasma lipoprotein-lipids variation in both racial groups. We also used two site haplotype data (codons 55 and 192) to assess the combined contribution of the two polymorphisms to the risk of CHD. There was a strong linkage disequilibrium between the two polymorphic sites in both racial groups (P < 0.0001). While the haplotype data revealed no association with CHD in Chinese, the frequency of the BL haplotype was significantly higher (0.430 versus 0.311; P = 0.004) and the frequency of the AL haplotype was significantly lower (0.368 versus 0.483; P = 0.006) in Indian patients than controls. Since the B allele of the codon 192 polymorphism was shown to be an independent risk factor for CHD in Indians in our previous study, the positive association of the BL haplotype with CHD appears to be mediated by the B allele with no independent contribution from the codon 55 polymorphism.

Adult↗
PubMed1988

Genetic code development by stop codon takeover.

A novel theoretical consideration of the origin and evolution of the genetic code is presented. Code development is viewed from the perspective of simultaneously evolving codons, anticodons and amino acids. Early code structure was determined primarily by thermodynamic stability considerations, requiring simplicity in primordial codes. More advanced coding stages could arise as biological systems became more complex and precise in their replication. To be consistent with these ideas, a model is described in which codons become permanently associated with amino acids only when a codon-anticodon pairing is strong enough to permit rapid translation. Hence all codons are essentially chain-termination or "stop" codons until tRNA adaptors evolve having the ability to bind tightly to them. This view, which draws support from several lines of evidence, differs from the prevalent thinking on code evolution which holds that codons specifying newer amino acids were derived from codons encoding older amino acids.

Amino Acids↗
PubMed1997

A newly identified pattern of K-ras mutations at codons 12 and 13 is associated with long-term survival in colorectal cancer.

BACKGROUND: Although K-ras mutations reportedly occur in 40% to 60% of all colorectal carcinomas, the relationship between specific mutations and clinical outcome is unclear. The purpose of this study was to assess the frequency and types of K-ras mutations in 89 colorectal cancer patients, comparing groups with short-term (less than 5 years) and long-term (more than 10 years) survival. METHODS: The group was divided into four cohorts by survival and modified Dukes classification (Dukes B2 and C2). DNA was extracted from formalin-fixed paraffin-embedded archival material. Mutational status was analyzed using a modification of allele-specific-polymerase chain reaction. RESULTS: Mutations in codon 12 were found in 11.2% of tumors, and 83% of tumors had mutations in codon 13. Gly > Asp accounted for 85.2% of the mutations. Tumors with mutations in both codon 12 and codon 13 occurred significantly more frequently in the long-term (21.3%) versus the short-term (2.4%) survival group. Gly > Asp mutations in either codon were related to long-term survival, and 80% of long-term survivors with mutations in both codons had Gly > Asp mutations in both. CONCLUSIONS: Simultaneous mutation in codons 12 and 13 of the K-ras gene appears to be a positive prognostic indicator in colorectal cancer.

Adult↗
PubMed1996

K-ras codon 12 and 61 point mutations in bromodeoxyuridine- and N-nitrosomethylurea-induced rat renal mesenchymal tumors.

The mutagenic thymidine analog bromodeoxyuridine (BrdUrd) may incorrectly incorporate opposite deoxyguanine in DNA, then pair with deoxyadenosine during subsequent replication. It appears to preferentially target the 3'-G of 5'-NGGN-3' sequences in mammalian cells in culture to induce G-->A transitions. Ras genes should therefore be vulnerable to activation by mutation at glycine codons 12 (GGT) and/or 13 (GGC) by misincorporation of BrdUrd. There is limited evidence that BrdUrd may be carcinogenic or co-carcinogenic in rats: three renal mesenchymal tumors, a tumor known to be associated with activating mutations in the c-K-ras-2 oncogene, were reported in 87 rats treated with BrdUrd alone, while N-nitrosomethylurea (NMU) alone or NMU + BrdUrd resulted in incidences of 12/52 and 26/76, respectively, against a zero incidence in untreated rats. We analyzed renal mesenchymal tumors from rats treated with BrdUrd for mutations in K-ras exons 1 and 2 and compared the prevalence and spectrum of mutations with those found in comparable tumors induced with NMU. DNAs from 22 paraffin-embedded renal mesenchymal tumors from rats treated 12-15 months earlier with BrdUrd (three specimens) or NMU (11 specimens) or both agents sequentially (eight specimens) were amplified by PCR. The base sequence of codons 12-13 and 59-63 of K-ras was determined by the dideoxynucleotide method. Sequencing results were confirmed by allele-specific oligonucleotide hybridization. Two of three tumors that appeared in rats given BrdUrd alone contained both a codon 12 GGT-->GAT transition and a codon 61 CAA-->CTA transversion. One tumor induced by NMU alone also showed a codon 12 GGT-->GAT mutation, while only wild type sequence could be demonstrated in the codon 12-13 region in the remaining ten such tumors. Three NMU-induced tumors also showed codon 61 CAA-->CTA mutations, while the remaining tumors had wild type sequence. While the GGT-->GAT transitions identified in tumors from BrdUrd-treated rats are consistent with BrdUrd mutagenesis by misincorporation, the co-occurrence of CAA-->CTA transversions, the overall low prevalence of mutations, and the lack of any difference in mutation spectrum between tumors induced by NMU and those that occurred in BrdUrd-treated rats suggests that in both groups the mutations that did occur did not result from a direct effect of either agent.

Adenine↗
PubMed1998

Codon usage and gene function are related in sequences of Arabidopsis thaliana.

In this paper, the relationship between codon usage and the physiological pattern of expression of a gene is investigated while considering a dataset of 815 nuclear genes of Arabidopsis thaliana. Factorial Correspondence Analysis, a commonly used multivariate statistical approach in codon usage analysis, was used in order to analyse codon usage bias gene by gene. The analysis reveals a single major trend in codon usage among genes in Arabidopsis. At one end of the trend lie genes with a highly G/C biased codon usage. This group contains mainly photosynthetic and housekeeping genes which are known to encode the most abundant proteins of the vegetal cell. At the other extreme lie genes with a weaker A/T-biased codon usage. This group contain genes with various functions which exhibits most of the time a strong tissue-specific pattern of expression in relation, for example, to stress conditions. These observations were confirmed by the detailed analysis of codon usage in the multigene family of tubulins and appear to be general in plant species, even as distant from Arabidopsis thaliana as a monocotyledonous plant such as maize.

Arabidopsis↗
PubMed2000

Nucleotides of 18S rRNA surrounding mRNA codons at the human ribosomal A, P, and E sites: a crosslinking study with mRNA analogs carrying an aryl azide group at either the uracil or the guanine residue.

The 18S rRNA environment of the mRNA at the decoding site of human 80S ribosomes has been studied by cross-linking with derivatives of hexaribonucleotide UUUGUU (comprising Phe and Val codons) that carried a perfluorophenylazide group either at the N7 atom of the guanine or at the C5 atom of the 5'-terminal uracil residue. The location of the codons on the ribosome at A, P, or E sites has been adjusted by the cognate tRNAs. Three types of complexes have been obtained for each type derivative, namely, (1) codon UUU and Phe-tRNAPhe at the P site (codon GUU at the A site), (2) codon UUU and tRNAPhe at the P site and PheVal-tRNAVal at the A site, and (3) codon GUU and Val-tRNAVal at the P site (codon UUU at the E site). This allowed the placement of modified nucleotides of the mRNA analog at positions -3, +1, or +4 on the ribosome. Mild UV irradiation resulted in tRNA-dependent crosslinking of the mRNA analogs to the 18S rRNA. Nucleotide G961 crosslinked to mRNA position -3, nucleotide G1207 to position +1, and A1823 together with A1824 to position +4. All of these nucleotides are located in the most strongly conserved regions of the small subunit RNA structure, and correspond to nucleotides G693, G926, G1491, and A1492 of bacterial 16S rRNA. Three of them (with the exception of G1491) had been found earlier at the 70S ribosomal decoding site. The similarities and differences between the 16S and 18S rRNA decoding sites are discussed.

Anticodon↗