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At least 1,693 records · Page 94Linked to original sources
PubMed2002

Codon bias differentiates between the duplicated amylase loci following gene duplication in Drosophila.

We examined the pattern of synonymous substitutions in the duplicated Amylase (Amy) genes (called the Amy1- and Amy3-type genes, respectively) in the Drosophila montium species subgroup. The GC content at the third synonymous codon sites of the Amy1-type genes was higher than that of the Amy3-type genes, while the GC content in the 5'-flanking region was the same in both genes. This suggests that the difference in the GC content at third synonymous sites between the duplicated genes is not due to the temporal or regional changes in mutation bias. We inferred the direction of synonymous substitutions along branches of a phylogeny. In most lineages, there were more synonymous substitutions from G/C (G or C) to A/T (A or T) than from A/T to G/C. However, in one lineage leading to the Amy1-type genes, which is immediately after gene duplication but before speciation of the montium species, synonymous substitutions from A/T to G/C were predominant. According to a simple model of synonymous DNA evolution in which major codons are selectively advantageous within each codon family, we estimated the selection intensity for specific lineages in a phylogeny on the basis of inferred patterns of synonymous substitutions. Our result suggested that the difference in GC content at synonymous sites between the two Amy-type genes was due to the change of selection intensity immediately after gene duplication but before speciation of the montium species.

Amylases↗
PubMed2003

Protein evolution and codon usage bias on the neo-sex chromosomes of Drosophila miranda.

The neo-sex chromosomes of Drosophila miranda constitute an ideal system to study the effects of recombination on patterns of genome evolution. Due to a fusion of an autosome with the Y chromosome, one homolog is transmitted clonally. Here, I compare patterns of molecular evolution of 18 protein-coding genes located on the recombining neo-X and their homologs on the nonrecombining neo-Y chromosome. The rate of protein evolution has significantly increased on the neo-Y lineage since its formation. Amino acid substitutions are accumulating uniformly among neo-Y-linked genes, as expected if all loci on the neo-Y chromosome suffer from a reduced effectiveness of natural selection. In contrast, there is significant heterogeneity in the rate of protein evolution among neo-X-linked genes, with most loci being under strong purifying selection and two genes showing evidence for adaptive evolution. This observation agrees with theory predicting that linkage limits adaptive protein evolution. Both the neo-X and the neo-Y chromosome show an excess of unpreferred codon substitutions over preferred ones and no difference in this pattern was observed between the chromosomes. This suggests that there has been little or no selection maintaining codon bias in the D. miranda lineage. A change in mutational bias toward AT substitutions also contributes to the decline in codon bias. The contrast in patterns of molecular evolution between amino acid mutations and synonymous mutations on the neo-sex-linked genes can be understood in terms of chromosome-specific differences in effective population size and the distribution of selective effects of mutations.

Animals↗
PubMed1996

Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype.

Eight zidovudine-experienced subjects received zidovudine and didanosine for 30 weeks followed by 30 weeks of didanosine monotherapy. At study entry, plasma from 4 subjects had human immunodeficiency virus RNA pol T215Y/F mutant and 4 had codon 215 wild type. All 8 subjects had non-syncytium-inducing virus phenotype. Sustained 10-fold decreases in plasma RNA levels were seen only in subjects who initially had 215 wild type RNA, despite the development of a T215Y/F mutation during combination therapy. Virologic and immunologic benefits were maintained in this group with didanosine monotherapy. No subject developed a pol L74V codon mutation. Significant differences in plasma virus load and CD4 cell responses were seen in this zidovudine-didanosine combination pilot study relative to codon 215 genotype.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Penicillin-binding protein 2 genes of chromosomally-mediated penicillin-resistant Neisseria gonorrhoeae from Greece: screening for codon Asp-345A.

Low affinity of penicillin for altered penicillin-binding protein 2 (PBP 2) of Neisseria gonorrhoeae that are chromosomally resistant to penicillin (CMRNG) has been attributed, at least partly to the insertion of an additional aspartic acid (Asp-35A) codon in the penA gene. Oligonucleotide probes were used to detect the presence or absence of this extra amino-acid residue in 34 non-penicillinase producing N. gonorrhoeae with decreased susceptibility to penicillin (MICs 0.25-2 mg/L) and 11 strains sensitive to penicillin (MIC < or = 0.06 mg/L) isolated in Greece and previously characterized by auxotype and serovar. The Asp-345A codon was found in all CMRNG strains as well as in strains with intermediate resistance to penicillin, but was absent from all strains exhibiting an MIC of penicillin of < or = 0.03 mg/L. No association of the Asp-345A insertion to any particular auxotype or serovar was found. These results expand the previously reported correlation between the presence of the Asp-345A codon and reduced sensitivity to penicillin, and shows that this particular mutation is common among epidemiologically distinct CMRNG strains.

Amino Acid Sequence↗
PubMed2005

Ribosomal proteins cross-linked to the initiator AUG codon of a mRNA in the translation initiation complex by UV-irradiation.

Eukaryotic ribosomal proteins constituting the binding site for the initiator codon AUG on the ribosome at the translation initiation step were investigated by UV-induced cross-linking between protein and mRNA. The 80S-initiation complex was formed in a rabbit reticulocyte cell-free system in the presence of sparsomycin with radiolabeled Omega-fragment as a template, which was a 73-base 5'-leader sequence of tobacco mosaic virus RNA having AUG at the extreme 3'-terminal end and extended with 32pCp. Two radioactive peaks were sedimented by sucrose gradient centrifugation, one being the 80S initiation complex formed at the 3'-terminal AUG codon, and the other presumably a "disome" with an additional 80S ribosome bound at an upstream AUU codon, formed when Omega-fragment was incubated with sparsomycin [Filipowicz and Henni (1979) Proc. Natl. Acad. Sci. USA 76, 3111-3115]. Cross-links between ribosomal proteins and the radiolabeled Omega-fragment were induced in situ by UV-irradiation at 254 nm. After extensive nuclease digestion of the complexes, ribosomal proteins were separated by two-dimensional gel electrophoresis. Autoradiography identified the proteins S7, S10, S25, S29, and L5 of the 80S initiation complex and S7, S25, S29 and L5 of that in the disome as 32P-labeled proteins. Together with the results of cross-linking experiments of other investigators and recently solved crystal structures of prokaryotic ribosomes, the spatial arrangement of eukaryotic ribosomal proteins at the AUG-binding domain is discussed.

Animals↗
PubMed2003

Effect of strong directional selection on weakly selected mutations at linked sites: implication for synonymous codon usage.

The fixation of weakly selected mutations can be greatly influenced by strong directional selection at linked loci. Here, I investigate a two-locus model in which weakly selected, reversible mutations occur at one locus and recurrent strong directional selection occurs at the other locus. This model is analogous to selection on codon usage at synonymous sites linked to nonsynonymous sites under strong directional selection. Two approximations obtained here describe the expected frequency of the weakly selected preferred alleles at equilibrium. These approximations, as well as simulation results, show that the level of codon bias declines with an increasing rate of substitution at the strongly selected locus, as expected from the well-understood theory that selection at one locus reduces the efficacy of selection at linked loci. These solutions are used to examine whether the negative correlation between codon bias and nonsynonymous substitution rates recently observed in Drosophila can be explained by this hitchhiking effect. It is shown that this observation can be reasonably well accounted for if a large fraction of the nonsynonymous substitutions on genes in the data set are driven by strong directional selection.

Alleles↗
PubMed2004

Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage.

In mammals divergence at fourfold degenerate sites in codons (K(4)) and intronic sequence (K(i)) are both used to estimate the mutation rate, under the supposition that both evolve neutrally. Does it matter which of these we use? Using either class of sequence can be defended because (1) K(4) is the same as K(i) (at least in rodents) and (2) there is no selectively driven codon usage (hence no systematic selection on third sites). Here we re-examine these findings using 560 introns (for 136 genes) in the mouse-rat comparison, aligned by eye and using a new maximum likelihood protocol. We find that the rate of evolution at fourfold sites and at intronic sites is similar in magnitude, but only after eliminating putatively constrained sites from introns (first introns and sites flanking intron-exon junctions). Any approximate congruence between the two rates is not, however, owing to an underlying similarity in the mode of sequence evolution. Some dinucleotides are hypermutable and differently abundant in exons and introns (e.g., CpGs). More importantly, after controlling for relative abundance, all dinucleotides starting with A or T are more prevalent in mismatches in exons than in introns, whereas C-starting dinucleotides (except CG) are more common in introns. Although C content at intronic sites is lower than at flanking fourfold sites, G content is similar, demonstrating that there exists a strong strand-specific preference for C nucleotides that is unique to exons. Transcription-coupled mutational processes and biased gene conversion cannot explain this, as they should affect introns and flanking exons equally. Therefore, by elimination, we propose this to be strong evidence for selectively driven codon usage in mammals.

Animals↗
PubMed2005

Levels of H-ras codon 61 CAA to AAA mutation: response to 4-ABP-treatment and Pms2-deficiency.

DNA mismatch repair (MMR) deficiencies result in increased frequencies of spontaneous mutation and tumor formation. In the present study, we tested the hypothesis that a chemically-induced mutational response would be greater in a mouse with an MMR-deficiency than in the MMR-proficient mouse models commonly used to assay for chemical carcinogenicity. To accomplish this, the induction of H-ras codon 61 CAA-->AAA mutation was examined in Pms2 knockout mice (Pms2-/-, C57BL/6 background) and sibling wild-type mice (Pms2+/+). Groups of five or six neonatal male mice were treated with 0.3 micromol 4-aminobiphenyl (4-ABP) or the vehicle control, dimethylsulfoxide. Eight months after treatment, liver DNAs were isolated and analysed for levels of H-ras codon 61 CAA-->AAA mutation using allele-specific competitive blocker-PCR. In Pms2-proficient and Pms2-deficient mice, 4-ABP treatment caused an increase in mutant fraction (MF) from 1.65x10(-5) to 2.91x10(-5) and from 3.40x10(-5) to 4.70x10(-5), respectively. Pooling data from 4-ABP-treated and control mice, the approximately 2-fold increase in MF observed in Pms2-deficient as compared with Pms2-proficient mice was statistically significant (P=0.0207) and consistent with what has been reported previously in terms of induction of G:C-->T:A mutation in a Pms2-deficient background. Pooling data from both genotypes, the increase in H-ras MF in 4-ABP-treated mice, as compared with control mice, did not reach the 95% confidence level of statistical significance (P=0.0606). The 4-ABP treatment caused a 1.76-fold and 1.38-fold increase in average H-ras MF in Pms2-proficient and Pms2-deficient mice, respectively. Furthermore, the levels of induced mutation in Pms2-proficient and Pms2-deficient mice were nearly identical (1.26x10(-5) and 1.30x10(-5), respectively). We conclude that Pms2-deficiency does not result in an amplification of the H-ras codon 61 CAA-->AAA mutational response induced by 4-ABP.

Adenosine Triphosphatases↗
PubMed1984

Codon usage can affect efficiency of translation of genes in Escherichia coli.

By inserting synthetic oligonucleotides into a highly expressed gene in E. coli it has been shown that unfavourable codon usage can reduce the maximum translation rate of a protein. However, in the case of the codon used (AGG), a significant effect on translation was only seen at very high transcription rates from a gene containing multiple copies of the unfavourable codon.

Bacterial Proteins↗
PubMed1984

Nucleotide sequence of a 1.1 kb fragment of the pea chloroplast genome containing three tRNA genes, one of which is located within an open reading frame of 91 codons.

The nucleotide sequence of a 1082 bp fragment from the pea (Pisum sativum) chloroplast genome is presented. This fragment contains genes for tRNAGlu, tRNATyr and tRNAAsp as well as an open reading frame (ORF) of 91 codons on one strand and two ORFs of 52 and 59 codons on the complementary strand. The tRNAAsp gene is located entirely within the ORF of 91 codons. The first 366 bp of the fragment correspond to 376 bp at one end of a recently published (1) sequence from the broad bean (Vicia faba) chloroplast genome. These regions contain the tRNAGlu and tRNATyr genes, which are identical and separated by 60 bp in both species. These two genes are probably cotranscribed. The intergenic regions in the corresponding segments from the two species are, except for a 10 bp deletion in the pea sequence, 94% homologous.

Base Composition↗
PubMed1985

Deletion of C-terminal amino acid codons of PhiX174 gene E: effect on its lysis inducing properties.

The lysis gene E of bacteriophage PhiX174 has been subjected to deletion and fusion analysis. Deletions of 11 to 90% of gene E specific nucleotides coding for to C-terminal region of the gene product were cloned under transcriptional control of lambda pL. For this purpose plasmid pSU1 was constructed which carries an extended polylinker region downstream of pL. Depending on the number of nucleotides after the last gene E specific codon, various C-terminal segments of protein E were replaced by 4, 5, 53 or 314 unrelated amino acids. Functional analysis for lysis inducing properties of the various gene E mutants revealed that the final 9 codons of the gene could be deleted without loss of function. However, replacements of 19 or more C-terminal codons eliminated gene E activity. Although the functional site of the gene E product is located within the N-terminal half of the polypeptide, the C-terminal part of the protein appears to exhibit severe influence on conformation and/or regulation of the functional site.

Amino Acid Sequence↗
PubMed1986

The MURFI linker for multiple reading frame insertion of a sense or nonsense codon into DNA.

Blunt-end palindromic DNA linkers with a central restriction site have been designed for the multiple reading frame insertion (abbreviated MURFI) of a sense or nonsense codon into DNA. We have utilized an amber MURFI linker, 5'CTAG TCTAGA CTAG3' to disrupt the lacZ gene, yielding truncated beta-galactosidase proteins. Conditional disruption of the tetr gene in E. coli has also been demonstrated. Nonsense codon MURFI linkers permit conditional fusion of multiple gene products while sense codon linkers can add structural elements (e.g. beta-turn, cationic segment, hydrophobic segment) or a desired amino acid to a protein (e.g. methionine, cysteine). Shotgun or alternatively site-directed insertion of the symmetric linkers is possible. The over-all length of the linker may be adjusted to retain the original reading frame, matching nucleotide additions or subtractions at recipient DNA sites. If a linker restriction site occurs elsewhere in the target DNA, single linker copies may still be inserted using non-phosphorylated linkers.

Base Sequence↗
PubMed1986

Alpha-thalassemia due to the deletion of nucleotides -2 and -3 preceding the AUG initiation codon affects translation efficiency both in vitro and in vivo.

We previously hypothesized that a 2 nucleotide deletion, causing a A-greater than C change at position -3 preceding the ATG initiation codon of alpha globin gene, reduced translation efficiency of alpha globin mRNA and was responsible for a form of alpha + thalassemia displayed by an Algerian patient. We presently show that this deletion leads to a 30-45% reduction in translation efficiency of synthetic alpha globin mRNA in rabbit reticulocyte lysate. In other experiments, we constructed alpha/G gamma hybrid globin genes in which the 3' end of normal or mutated alpha globin genes downstream to the ATG initiation codon was substituted by the 3' part of a G gamma globin gene. COS cells transfected with either of these 2 hybrid genes were shown to synthesize a similar amount of alpha/G gamma hybrid mRNAs but 50% less G gamma globin when transfected with the alpha/G gamma hybrid gene carrying the deletion. These results definitively establish that the 2 nucleotide deletion reduces translation efficiency by 30-50%. This contrasts with the 93% reduction induced by a similar A-greater than C change at position -3 in the different nucleotide context preceding the ATG codon of the rat preproinsulin gene.

Base Sequence↗
PubMed1987

The human c-Kirsten ras gene is activated by a novel mutation in codon 13 in the breast carcinoma cell line MDA-MB231.

We have detected amplified human Ki-ras sequences in tumorigenic NIH 3T3 cells transfected with genomic DNA from the human breast carcinoma cell line MDA-MB231. Hybridization of synthetic oligonucleotides specific for human Ki-ras sequences showed a mutation at codon 13. The polymerase chain reaction with Ki-ras specific amplimers revealed a guanosine to adenosine transition at the second position of codon 13, resulting in a substitution of glycine by aspartic acid. The codon 13 mutation is also detected in one Ki-ras allele of the MDA-MB231 cell line.

Animals↗
PubMed1987

Adjustment of the tRNA population to the codon usage in chloroplasts.

In chloroplasts there is a correlation between the amounts of tRNAs specific for a given amino acid and the codons specifying this amino acid. Furthermore, for the amino acids coded for by more than one codon, the population of isoaccepting tRNAs is adjusted to the frequency of synonymous codons used in chloroplast protein genes. A comparison by two-dimensional gel electrophoresis of the tRNA populations extracted from chloroplasts and from chloroplast polysomes shows that all chloroplast tRNAs are involved in protein biosynthesis.

Chloroplasts↗
PubMed1989

Infectious TYMV RNA from cloned cDNA: effects in vitro and in vivo of point substitutions in the initiation codons of two extensively overlapping ORFs.

Full-length cDNA of the 6.3 kb turnip yellow mosaic virus (TYMV) genome was placed between a T7 promoter and a unique Hind III site. In vitro transcription of Hind III-linearized DNA of clone pTYMC yielded full-length RNA transcripts. In inoculations of Chinese cabbage protoplasts and plants, capped transcripts and virion RNA had similar specific infectivities and produced similar systemic symptoms. We have used the pTYMC clone in studies of the expression of two overlapping open reading frames (1.9 kb and 5.5 kb ORFs) by making mutants with alterations in the initiation codons. Evidence is presented from in vitro translations of mutant and wild type RNAs that both ORFs are expressed from TYMV RNA. A mutant in the initiation codon of the 5.5 kb ORF did not replicate in protoplasts, while mutants in the initiation codon of the 1.9 kb ORF replicated at low levels. The two groups of mutants were not able to complement each other.

Brassica↗
PubMed1989

Expression of tetanus toxin fragment C in E. coli: high level expression by removing rare codons.

Tetanus toxin fragment C had been previously expressed in Escherichia coli at 3-4% cell protein. The codon bias for tetanus toxin in Clostridium tetani is very different from that of highly expressed homologous genes in E. coli, resulting in the presence of many rare E. coli codons in the sequence encoding fragment C. We have replaced the coding sequence by sequence optimized for codon usage in E. coli, and show that the expression of fragment C is increased. Although the level of mRNA also increased this appeared to be a secondary consequence of more efficient translation. Complete sequence replacement increased expression to approximately 11-14% cell protein but only after the promoter strength had been improved.

Amino Acid Sequence↗
PubMed1991

Ribosomes containing the C1054-deletion mutation in E. coli 16S rRNA act as suppressors at all three nonsense codons.

It was established some time ago that the deletion of base C1054 in E. coli 16S rRNA specifically affects UGA-dependent termination of translation. Based on this observation, a model for the termination event was proposed in which the UGA nonsense codon on the mRNA base-pairs with a complementary motif in 'helix 34' of the 16S rRNA, thus potentially providing a recognition signal for the binding of the release factor. This model has been re-examined here and evidence is presented which demonstrates that ribosomes containing the C1054 delta mutation enhance the activity of suppressors of both UAG and UAA termination codons introduced into the host. The results do not support the nonsense codon-16S rRNA base pairing model, and rather imply a more general involvement of 'helix 34' in the translation termination reactions.

Codon↗