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PubMed1985

Utilization of internal AUG codons for initiation of protein synthesis directed by mRNAs from normal and mutant genes encoding herpes simplex virus-specified thymidine kinase.

Previous studies (H.S. Marsden, L. Haarr, and C.M. Preston, J. Virol. 46:434-445, 1983) have shown that at least three polypeptides, with molecular weights of 43,000, 39,000, and 38,000, are encoded by the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) gene. It has been suggested that the 39,000- and 38,000-molecular-weight polypeptides arise from preinitiation complexes bypassing the first and second AUG codons before commencement of translation since, according to previous work (M. Kozak, Nucleic Acids Res. 9:5233-5252, 1981), these codons are not of the most efficient structure for initiation. This possibility was investigated by using specific herpes simplex virus mutants with alterations in the TK gene. Mutant TK4 has an amber mutation between the first and second AUG codons, whereas mutant delta 1 has a deletion which removes the first AUG codon but leaves other AUG codons, as well as transcriptional promoter sequences, intact. Both mutants synthesized only the 39,000- and 38,000-molecular-weight polypeptides, and the amounts produced were normal in TK4-infected cells but increased in delta 1-infected cells. Furthermore, the levels of TK produced after infection with the mutant viruses correlated with the amounts of the 39,000- and 38,000-molecular-weight polypeptides synthesized. The 43,000-, 39,000-, and 38,000-molecular-weight polypeptides were shown to be related by their positive reaction with anti-TK serum in both immunoprecipitation and immunoblotting experiments. The production of the 39,000- and 38,000-molecular-weight polypeptides through bypassing of the first AUG codon was examined by hybrid arrest experiments with a DNA fragment complementary to only 50 bases at the 5' terminus of TK mRNA. This fragment arrested the synthesis of the 30,000- and 38,000-molecular-weight polypeptides when annealed to mRNA from wild-type HSV-1- or TK4-infected cells, showing that those polypeptides arise from an mRNA initiated upstream from the first AUG codon. mRNA from cells infected with mutant delta 1, which lacks DNA sequences upstream from the first AUG, was not affected by the 50-base-pair fragment. The data therefore confirm that three polypeptides encoded by the HSV-1 TK gene arise by differential use of in-phase AUG codons for the initiation of protein synthesis. This mechanism for the production of related but distinct polypeptides has not previously been demonstrated in a eucaryotic system, and the implications for the regulation of TK enzyme activities are discussed.

Cell Line↗

PubMed1994

Differential response of human cells to deletions and stop codons in the gamma(1)34.5 gene of herpes simplex virus.

Earlier studies have shown that herpes simplex virus mutants lacking the gamma(1)34.5 gene are totally avirulent on intracerebral inoculation of the virus into mice and induce premature shutoff of protein synthesis in human neuroblastoma (SK-N-SH) cells but not in Vero cells. We report the following. (i) Whereas deletion mutant R3616, lacking 1,000 bp of the gamma(1)34.5 gene, caused premature shutoff of protein synthesis in both SK-N-SH and human foreskin fibroblasts (HFF), mutants R4009 and R930 (mutant F), carrying stop codons in all six frames, 27 and 210 codons from the initiation codon of the gamma(1)34.5 genes, respectively, induced shutoff of protein synthesis in SK-N-SH cells but not in HFF. The differences in behavior between the R3616 deletion and R4009 stop codon mutants cannot be attributed to differences in the rate of induction of premature shutoff of protein synthesis and the multiplicity of infection. HFF do not produce detectable truncated gamma(1)34.5 protein or truncated mRNA. (ii) Some clonal lines of SK-N-SH cells carrying a gamma(1)34.5 gene driven by a metallothionein promoter express the gamma(1)34.5 gene constitutively and do not require induction by cadmium to complement the gamma(1)34.5- virus. One clonal cell line complements the gamma(1)34.5- virus only after induction by cadmium. These results are consistent with previous conclusions that the phenotype of premature shutoff of protein synthesis is associated with absence of the gamma(1)34.5 protein and indicate that the amounts of gamma(1)34.5 protein necessary to complement the gamma(1)34.5- viruses are small. We conclude that human cells differ in the manner in which they respond to the presence of stop codons. Shutoff of protein synthesis in HFF infected with the stop codon mutants could have been precluded by small amounts of gamma(1)34.5 protein produced by splicing out of an intron containing the stop codon, downstream initiation of translation, or tRNA suppression of the stop codon.

Animals↗

PubMed1992

The suil suppressor locus in Saccharomyces cerevisiae encodes a translation factor that functions during tRNA(iMet) recognition of the start codon.

We initiated a genetic reversion analysis at the HIS4 locus to identify components of the translation initiation complex that are important for ribosomal recognition of an initiator codon. Three unlinked suppressor loci, suil, sui2, and SUI3, that restore expression of both HIS4 and HIS4-lacZ in the absence of an AUG initiator codon were identified. In previous studies, it was demonstrated that the sui2 and SUI3 genes encode mutated forms of the alpha and beta subunits, respectively, of eukaryotic translation initiation factor 2 (eIF-2). In this report, we describe the molecular and biochemical characterizations of the sui1 suppressor locus. The DNA sequence of the SUI1+ gene shows that it encodes a protein of 108 amino acids with a calculated Mr of 12,300. The sui1 suppressor genes all contain single base pair changes that alter a single amino acid within this 108-amino-acid sequence. sui1 suppressor strains that are temperature sensitive for growth on enriched medium have altered polysome profiles at the restrictive temperature typical of those caused by alteration of a protein that functions during the translation initiation process. Gene disruption experiments showed that the SUI1+ gene encodes an essential protein, and antibodies directed against the SUI1+ coding region identified a protein with the predicted Mr in a ribosomal salt wash fraction. As observed for sui2 and SUI3 suppression events, protein sequence analysis of His4-beta-galactosidase fusion proteins produced by sui1 suppression events indicated that a UUG codon is used as the site of translation initiation in the absence of an AUG start codon in HIS4. Changing the penultimate proline codon 3' to UUG at his4 to a Phe codon (UUC) blocks aminopeptidase cleavage of the amino-terminal amino acid of the His4-beta-galactosidase protein, as noted by the appearance of Met in the first cycle of the Edman degradation reaction. The appearance of Met in the first cycle, as noted, in either a sui1 or a SUI3 suppressor strain showed that the mechanism of suppression is the same for both suppressor genes and allows the initiator tRNA to mismatch base pair with the UUG codon. This suggests that the Sui1 gene product performs a function similar to that of the beta subunit of eIF-2 as encoded by the SUI3 gene. However, the Sui1 gene product does not appear to be a required subunit of eIF-2 on the basis of purification schemes designed to identify the GTP-dependent binding activity of eIF-2 for the initiator tRNA. In addition, suppressor mutations in the sui1 gene, in contrast to suppressor mutations in the sui2 or SUI3 gene, do not alter the GTP-dependent binding activity of the eIF-2. The simplest interpretation of these studies is that the sui1 suppressor gene defines an additional factor that functions in concert with eIF-2 to enable tRNAiMet to establish ribosomal recognition of an AUG initiator codon.

Amino Acid Sequence↗

PubMed1994

Effect of sequence context at stop codons on efficiency of reinitiation in GCN4 translational control.

Translational control of the GCN4 gene involves two short open reading frames in the mRNA leader (uORF1 and uORF4) that differ greatly in the ability to allow reinitiation at GCN4 following their own translation. The low efficiency of reinitiation characteristic of uORF4 can be reconstituted in a hybrid element in which the last codon of uORF1 and 10 nucleotides 3' to its stop codon (the termination region) are substituted with the corresponding nucleotides from uORF4. To define the features of these 13 nucleotides that determine their effects on reinitiation, we separately randomized the sequence of the third codon and termination region of the uORF1-uORF4 hybrid and selected mutant alleles with the high-level reinitiation that is characteristic of uORF1. The results indicate that many different A+U-rich triplets present at the third codon of uORF1 can overcome the inhibitory effect of the termination region derived from uORF4 on the efficiency of reinitiation at GCN4. Efficient reinitiation is not associated with codons specifying a particular amino acid or isoacceptor tRNA. Similarly, we found that a diverse collection of A+U-rich sequences present in the termination region of uORF1 could restore efficient reinitiation at GCN4 in the presence of the third codon derived from uORF4. To explain these results, we propose that reinitiation can be impaired by stable base pairing between nucleotides flanking the uORF1 stop codon and either the tRNA which pairs with the third codon, the rRNA, or sequences located elsewhere in GCN4 mRNA. We suggest that these interactions delay the resumption of scanning following peptide chain termination at the uORF and thereby lead to ribosome dissociation from the mRNA.

Base Sequence↗

PubMed1994

Ubiquitous and tenacious methylation of the CpG site in codon 248 of the p53 gene may explain its frequent appearance as a mutational hot spot in human cancer.

Cytosine methylation at CpG dinucleotides is thought to cause more than one-third of all transition mutations responsible for human genetic diseases and cancer. We investigated the methylation status of the CpG dinucleotide at codon 248 in exon 7 of the p53 gene because this codon is a hot spot for inactivating mutations in the germ line and in most human somatic tissues examined. Codon 248 is contained within an HpaII site (CCGG), and the methylation status of this and flanking CpG sites was analyzed by using the methylation-sensitive enzymes CfoI (GCGC) and HpaII. Codon 248 and the CfoI and HpaII sites in the flanking introns were methylated in every tissue and cell line examined, indicating extensive methylation of this region in the p53 gene. Exhaustive treatment of an osteogenic sarcoma cell line, TE85, with the hypomethylating drug 5-aza-2'-deoxycytidine did not demethylate codon 248 or the CfoI sites in intron 6, although considerable global demethylation of the p53 gene was induced. Constructs containing either exon 7 alone or exon 7 and the flanking introns were transfected into TE85 cells to determine whether de novo methylation would occur. The presence of exon 7 alone caused some de novo methylation to occur at codon 248. More extensive de novo methylation of the CfoI sites in intron 6, which contains an Alu sequence, occurred in cells transfected with a vector containing exon 7 and flanking introns. With longer time in culture, there was increased methylation at the CfoI sites, and de novo methylation of codon 248 and its flanking HpaII sites was observed. These de novo-methylated sites were also resistant to 5-aza-2'-deoxycytidine-induced demethylation. The frequent methylation of codon 248 and adjacent Alu sequence may explain the enhanced mutability of this site as a result of the deamination of the 5-methylcytosine.

Base Sequence↗

PubMed1980

Aberrations of the classic codon reading scheme during protein synthesis in vitro.

Using a protein synthesizing in vitro system programmed with MS2-RNA, the ability of alanine tRNAs with the anticodons U*GC (U* represents 5-oxyacetic acid uridine monophosphate) and IGC to read the alanine codons in the coat protein cistron of MS2 has been determined both under conditions of no competition, where the alanyl-tRNA used was the only aminoacylated tRNAAla present in the system, and in experiments where the two alanyl-tRNAs were competing against each other. Under conditions of no competition, each of the anticodons can read all four alanine codons. However, when the anticodons compete for the codon GCC, the anticodon IGC, which can read all three positions of the codon according to the rules of Watson-Crick base pairing, is considerably more efficient than U*GC, which misreads the codon by reading only the first two positions and presumably disregards the third nucleotide of the codon. The outcome of the competition experiments also reveals two apparent violations of the wobble restrictions: the anticodon U*GC reads the codon GUU almost as effectively as does the anticodon IGC, and IGC is almost as effective as U*GC in reading the codon GCG.

Alanine-tRNA Ligase↗

PubMed1994

The incidence and prognostic significance of mutations in codon 13 of the N-ras gene in acute myeloid leukemia.

To determine the incidence and prognostic significance of mutation in the N-ras gene in de novo acute myeloid leukemia (AML) we performed an analysis of bone marrow smears from 219 patients with de novo AML treated between 1984 and 1986 and followed for at least six years. DNA extracted from bone marrow smears taken at diagnosis was screened for the presence of mutations in codons 12 and 13 of exon 1 by using the polymerase chain reaction to insert an Hph1 restriction enzyme site into DNA. Presumptive mutations were confirmed by direct sequencing. Mutations were detected in a total of 26 patients (12%); in nine patients (4%) in codon 12 only, in ten patients (5%) in codon 13 only, and in seven patients (3%) in both codons. Mutations in codon 12 or codon 13 were not associated with any clinical features. Mutations in codon 12 had no prognostic significance but mutations in codon 13 were associated with an increased remission rate, a more durable remission, and a significantly prolonged survival which appeared to be independent of other prognostic factors.

Base Sequence↗

PubMed1993

Codons 12 and 13 of H-ras protooncogene interrupt the progression of DNA synthesis catalyzed by DNA polymerase alpha.

Mutagenesis of protooncogenes has been postulated to contribute to the initiation and progression of human cancer. Activating mutations in the H-ras gene are predominantly single-base substitutions and are most frequently identified at codons 12, 13, and 61. We have analyzed the effects of DNA sequence context at specific codons that are hot spots for ras mutation with respect to abnormalities in copying by purified DNA polymerase alpha, a major eucaryotic replication enzyme. Exon 1 of H-ras gene was inserted into M13 mp19, single-stranded DNA constructs were isolated, and the progression of synthesis by polymerase alpha was measured. Strong termination sites were found in codons 12 and 13. Pausing at these codons is abolished when the template is mutated at the middle base of codon 12, the same alteration that converts H-ras into an activated oncogene. Resistance of codon 12 in double-stranded constructs to digestion with restriction enzymes and computer investigation of the ras sequence suggest that these termination sites are in a region of secondary structure. The frequency of sequence alterations within DNA chains that have been extended past codons 12 and 13 was found to be < 0.01. We consider a variety of mechanisms by which the potential secondary structure involving codons 12 and 13 may contribute to the pausing of DNA polymerase alpha and to the generation of clustered mutations at this site.

Base Sequence↗

PubMed1996

[Analysis of apolipoprotein gene family in codon space--non-random selection of nucleotide changes in evolution].

The choice of nucleotide changes in DNA evolution can be either selectively neutral or biased. To study how apolipoprotein gene selects the nucleotide substitutions in the course of evolution, a codon space is constructed in which its DNA sequence can be mapped as a matrix of nucleotide frequencies in three codon positions. Accordingly, a number of methods that measure the nonrandomness of nucleotide distribution in codon space are developed based on maximum entropy techniques to define the nature of nucleotide change selection in evolution. By these methods, we demonstrated that the nucleotide composition in 1st and 3rd codon position of apolipoprotein genes is highly nonrandom, which appears to be a result of non-neutral selection of codon positions by adenosine and thymidine. In addition, this paper is also concerned in the divergence of synonymos codon usage and its correlation to taxonomic distances among species. As a result, a codon usage clock was reported in apolipoprotein A-I. Our studies suggest that non-random selection of nucleotide changes in codon space may represent an evolutionary characteristics of apolipoprotein genes.

Animals↗

PubMed2026

Comprehensive analysis of synonymous codon usage bias and evolutionary dynamics in the chloroplast genomes of eight Coptis species.

Coptis is a medically important genus renowned for producing valuable isoquinoline alkaloids. Although its chloroplast genomes encode key components for photosynthesis and plastid gene expression, the evolutionary constraints acting on their coding sequences and synonymous codon usage remain poorly resolved. Here, we combined a transparent taxon-level sampling strategy with comparative analyses of chloroplast CDSs from eight Coptis taxa. We quantified nucleotide composition, relative synonymous codon usage, effective number of codons, neutrality and PR2 patterns, and correspondence analysis, and then integrated these results with a core-CDS distance analysis and gene-wise pairwise dN/dS estimates. The chloroplast genomes showed a conserved AT-rich composition, especially at the third codon position (GC3 approximately 30.3-30.8%), with a consistent GC1 > GC2 > GC3 trend. Thirty preferred codons were detected, 28 ending in A/T, and eleven optimal codons were shared across the genus. The core-CDS distance analysis recovered a close relationship between C. chinensis and C. chinensis var. brevisepala, whereas most coding genes showed dN/dS values below one, consistent with pervasive purifying constraint. Across 48 consistently filtered CDSs, GC3s was negatively associated with mean dN (Spearman rho = -0.404, P = 0.00439) and CAI was positively associated with mean dN (rho = 0.303, P = 0.0361), whereas the remaining associations were not significant (all P > = 0.0972). These results extend codon-usage analysis by linking synonymous-site composition to coding-sequence evolution within Coptis, while providing a hypothesis-generating resource for future plastid engineering studies.

Genome, Chloroplast↗

PubMed1998

UGA codon position affects the efficiency of selenocysteine incorporation into glutathione peroxidase-1.

A UGA codon and a selenocysteine insertion sequence in the 3'-untranslated region are the only established mRNA elements necessary for selenocysteine (Sec or U) incorporation during translation. These two elements, however, do not universally confer efficient Sec incorporation. The objective of this study was to systematically examine the effect of UGA codon position on efficiency of Sec insertion. In a glutathione peroxidase-1 (F-GPX1) expression vector, the UGA at the native position (U47) was mutated to a cysteine codon, and codons for Ser-7, Ser-12, Ser-18, Ser-29, Ser-45, Ser-93, Cys-154, Val-172, Ser-178, and Ser-195 were individually mutated to UGA and transiently expressed in COS-7 cells. 75Se incorporation at the 11 positions was 31, 72, 54, 105, 90, 100, 146, 135, 13, 11, and 43%, respectively, of 75Se incorporation at U47, suggesting that Sec is more efficiently incorporated at UGA codons positioned in the middle of the coding region rather than close to the 5' or 3' ends. Ribonuclease protection showed that these differences were not due to differences in mRNA level. When the green fluorescence protein (GFP) coding region was placed in-frame at the 5' or 3' ends of the coding region in F-GPX1 to produce chimeric 50-51-kDa GFP/GPX1 proteins, Sec incorporation at UGA codons, formerly close to the 5' or 3' ends, was increased to levels comparable to the UGA at U47. Insertion of GFP after the UAA-stop was just as effective in increasing Sec insertion efficiency as GFP inserted before the stop. These studies used a recombinant expression model that incorporated Sec at non-native UGA codons at rates equal to those of endogenous glutathione peroxidase-1 and showed that the efficiency of Sec incorporation can be modulated by UGA position; Sec incorporation at high efficiency appears to require that the UGA be >21 nucleotides from the AUG-start and >204 nucleotides from the selenocysteine insertion sequence element.

3' Untranslated Regions↗

PubMed1990

Glycine to aspartic acid mutations at codon 13 of the c-Ki-ras gene in human gastrointestinal cancers.

Point mutations of c-ras genes were analyzed in human gastrointestinal cancers. DNA obtained from the tissues was amplified by polymerase chain reaction and then analyzed by dot blot hybridization assay with oligonucleotide probes to detect mutations at codons 12, 13, and 61 of c-Ki-ras, c-Ha-ras, and c-N-ras. In two of 25 cases of stomach cancer point mutations at codon 13 of c-Ki-ras were found. In colorectal cancer, eight of 30 cases showed mutations: four cases of codon 12 and one case at codon 13 of c-Ki-ras and two cases at codon 61 and one case at codon 13 of c-N-ras. These results may indicate involvement of a wide variety of c-ras gene point mutations, in addition to those at codon 12 of c-Ki-ras, in oncogenesis of human gastrointestinal cancers. In all three mutations of c-Ki-ras at codon 13 which had been seldom found in human cancers, glycine to aspartic acid mutations due to identical G to A transition at the second nucleotide were observed.

Aspartic Acid↗

PubMed1995

Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases.

BACKGROUND: The frequency and clinicopathologic significance of the K-ras gene point mutation in stomach cancer remain to be defined. METHODS: The authors investigated the frequency of K-ras codon 12 point mutations in stomach cancer using a sensitive polymerase chain reaction (PCR)-based method in 140 samples and correlated the findings with various clinicopathologic characteristics of the patients. RESULTS: The overall frequency of K-ras codon 12 point mutations in stomach cancer was 7.9% (11/140). DNA sequencing of nine cases with K-ras codon 12 point mutations identified seven cases with a single-base substitution of GGT to AGT (glycine to serine) and two with single-base substitution of GGT to AGT (aspartic acid). Tumors located in the upper third of the stomach had a significantly higher frequency of K-ras codon 12 mutations (3/8, 37.5%) compared with tumors located in the middle (4/29, 13.8%) or lower (3/99, 3.0%) thirds of the stomach (P = 0.001). No significant difference was observed in the frequency of K-ras codon 12 mutations in terms of other various clinicopathologic characteristics including tumor DNA ploidy and S-phase fraction. After a median follow-up of 26 months, disease free and overall survival were not significantly different between patients with stomach cancer with or without K-ras codon 12 mutation. Among eight patients with stomach cancer located in the upper part of the stomach, none of the three patients with K-ras gene-mutated tumors died versus four of five with tumors without K-ras gene mutations (P = 0.064). CONCLUSIONS: K-ras codon 12 point mutations are uncommon in stomach cancer (7.9%). There was significant correlation between K-ras mutations and vertical tumor location in the stomach, suggesting that different mechanisms may play a role in the pathogenesis of stomach cancer according to the location of tumors in the stomach.

Adult↗

PubMed1994

A graphic approach to analyzing codon usage in 1562 Escherichia coli protein coding sequences.

The occurrence frequencies of the four bases (adenine, cytosine, guanine and thymine) at each of the three codon positions for 1562 Escherichia coli protein coding sequences have been calculated. The 1562 x 4 x 3 = 18,744 data thus obtained have been analyzed by a graphic method in which the four base occurrence frequencies at each codon position for each coding sequence are represented by a point in a three-dimensional space. Thus, the 18,744 data, which would otherwise occupy several printed pages, can be intuitively displayed by a graphy. The point distribution pattern for each of the three codon positions has been analyzed. The results of our analysis indicate that the patterns for the first two codon positions reflect the origin for producing native folding structures of proteins. We thus come to the conclusion that the distribution patterns for the first two codon positions should be basically species-independent, as confirmed by studies for a number of other species. However, the distribution pattern for the third codon position is species-dependent. Based on the point distribution of the third codon position, six collective parameters have been defined to describe the overall feature of the pattern concerned. These collective parameters can be generally used to classify different species, and hence would be a useful vehicle for studies in taxonomy. In addition to E. coli, the collective parameters for a number of other species have been calculated and analyzed.

Animals↗

PubMed1996

Both codon context and leader length contribute to efficient expression of two overlapping open reading frames of a cucumber necrosis virus bifunctional subgenomic mRNA.

The importance of codon context and leader length in the translational regulation of p20 and p21 from the bifunctional 0.9-kb subgenomic mRNA cucumber necrosis virus was investigated. Nucleotide substitutions introduced into the -3 and +4 positions of the p21 AUG codon (where the A of the AUG is +1) verified that purines in these positions are favored and demonstrated the similar contribution of the -3 and +4 positions to the efficiency of initiation codon selection in plants. The effect of nucleotide substitutions in the +5 position, most clearly demonstrated when pyrimidines occupy the -3 and +4 positions, also provided direct insight into the influence of the +5 position in plants. The codon context of the upstream p21 initiation codon affected expression from the downstream p20 AUG codon. In addition, an increase in the length of the subgenomic mRNA leader decreased expression from the downstream p20 initiation site. These latter observations are in accordance with the "Kozak rules" for accession of internal AUG codons by leaky ribosomal scanning and provide the first example of an effect of leader length on the efficiency of translation initiation in a plant (viral) mRNA.

Base Sequence↗

PubMed1996

The influence of AUG codons in the hepatitis C virus 5' nontranslated region on translation and mapping of the translation initiation window.

The initiation of translation of hepatitis C virus (HCV) is cap-independent and mediated by an internal ribosome entry site (IRES) that is located in the 5' nontranslated region (5' NTR) of the viral genome. This 5' NTR is relatively long and folds into a complex structure involving multiple hairpins and a pseudoknot. Within the sequence encompassing the IRES there are several AUG triplets. Some of these AUG codons are conserved between HCV genotypes and the related pestiviruses. In this study the 5 AUG codons (positions 13, 32, 85, 96, and 215) that are present in the 5' NTR of the HCV H-strain have been mutagenized to determine their influence on HCV cap-independent translation. The effect of these mutations on the expression of a chloramphenicol acetyl transferase (CAT) gene was tested in vaccinia virus. vTF7-3 infected Hep2 cells transfected with plasmids for the expression of a monocistronic HCV 5' NTR-CAT mRNA. Mutating the AUG codons at positions 13, 32, and 215 does not have a significant effect on CAT expression, inactivating the AUG codons at either position 85 or position 96 severely impaired IRES function. To determine whether ribosomes scan the RNA to select the initiation site, AUG codons were inserted up- and downstream of the authentic HCV polyprotein translation initiation codon (position 342). Analysis of these mutants has revealed that the ribosome is unable to use an AUG codon that is placed either 7 nucleotides upstream or 8 nucleotides downstream of the inactivated AUG at position 342. These results indicate that when scanning is involved in the recognition of the translation initiating AUG, it is limited to a narrow region between nucleotides 335 and 350.

Chromosome Mapping↗

PubMed1991

Codon usage is imposed by the gene location in the transcription unit.

A characteristic profile of the fluctuations of codon usage is observed in bacteriophages and mitochondria. By following the DNA in the direction of transcription, one moves slowly from a region where selective pressure favours codons ending with C to a region where the bias is in favour of codons ending with T; then, abruptly, one again enters a region of codons ending in C. The transcription end point takes place in the area of abrupt change in codon usage. By comparing Drosophila yakuba and mouse mitochondrial genomes, it is possible to show that the strategy of codon usage for a given gene depends on its location along the transcription unit and not on the encoded protein. The choice of codons ending in T or C allows large scale variations of DNA stability which could regulate the speed of propagation of the RNA polymerase.

Animals↗

PubMed1995

Comparison of the patterns of codon usage and bias between Brugia, Echinococcus, Onchocerca and Schistosoma species.

Patterns of codon usage and bias were compared among taxa of the genera Brugia, Echinococcus, Onchocerca and Schistosoma by metric multidimensional scaling and three commonly used indices of bias: Nc, GC3S and B. The overall codon usage for each taxon was compared, as was the codon usage for each individual gene within the taxa. Differences in the patterns of codon usage observed between taxa were dependent on the overall base composition of the genes analysed. The codon usage of Echinococcus was distinct from that of the other taxa. Furthermore, the pattern of codon usage detected by the average codon usage summed across all genes for each taxon was not shown by all genes from that taxon.

Animals↗