Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “synonymous codon”

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 649 records · Page 36Linked to original sources
PubMed2002

Novel HLA-DRB1 alleles revealed by sequencing based typing, DRB1*04053 and DRB1*1143.

We report the discovery of two HLA-DRB1 alleles by sequencing based typing (SBT). DRB1*04053 differs from previously reported DRB1 alleles by a single synonymous nucleotide substitution, resulting in a unique polymorphism at codon 93. DRB1*1143 differs from previously identified DRB1 alleles by a single non-synonymous nucleotide substitution, resulting in a polymorphism observed in other DRB1 and DRB3 alleles1.

Alleles↗
PubMed1997

Analyses of frameshifting at UUU-pyrimidine sites.

Others have recently shown that the UUU phenylalanine codon is highly frameshift-prone in the 3'(rightward) direction at pyrimidine 3'contexts. Here, several approaches are used to analyze frameshifting at such sites. The four permutations of the UUU/C (phenylalanine) and CGG/U (arginine) codon pairs were examined because they vary greatly in their expected frameshifting tendencies. Furthermore, these synonymous sites allow direct tests of the idea that codon usage can control frameshifting. Frameshifting was measured for these dicodons embedded within each of two broader contexts: the Escherichia coli prfB (RF2 gene) programmed frameshift site and a 'normal' message site. The principal difference between these contexts is that the programmed frameshift contains a purine-rich sequence upstream of the slippery site that can base pair with the 3'end of 16 S rRNA (the anti-Shine-Dalgarno) to enhance frameshifting. In both contexts frameshift frequencies are highest if the slippery tRNAPhe is capable of stable base pairing in the shifted reading frame. This requirement is less stringent in the RF2 context, as if the Shine-Dalgarno interaction can help stabilize a quasi-stable rephased tRNA:message complex. It was previously shown that frameshifting in RF2 occurs more frequently if the codon 3'to the slippery site is read by a rare tRNA. Consistent with that earlier work, in the RF2 context frameshifting occurs substantially more frequently if the arginine codon is CGG, which is read by a rare tRNA. In contrast, in the 'normal' context frameshifting is only slightly greater at CGG than at CGU. It is suggested that the Shine-Dalgarno-like interaction elevates frameshifting specifically during the pause prior to translation of the second codon, which makes frameshifting exquisitely sensitive to the rate of translation of that codon. In both contexts frameshifting increases in a mutant strain that fails to modify tRNA base A37, which is 3'of the anticodon. Thus, those base modifications may limit frameshifting at UUU codons. Finally, statistical analyses show that UUU Ynn dicodons are extremely rare in E.coli genes that have highly biased codon usage.

Arginine↗
PubMed1993

Three new HLA-G alleles and their linkage disequilibria with HLA-A.

Three new allelic forms of the HLA-G DNA sequence (HLA-G*II, HLA-G*III, and HLA-G*IV) have been identified. With the HLA-G*I sequence (previously designated HLA 6.0) as a reference, HLA-G*II shows a silent (G-->A) mutation at the third base of codon 57, HLA-G*III bears a non-synonymous (A-->T), but conservative, (Thr-->Ser) substitution at the first base of codon 31, and HLA-G*IV shows two silent substitutions: (A-->T) at the third base of codon 107 and (G-->A) at the third base of codon 57. A rapid method of singling out each allele on genomic DNA has been developed by using polymerase chain reaction amplification followed by restriction endonuclease treatment. Also, more or less strong linkage disequilibria has been found between most HLA-A alleles and either HLA-G*I or *II, both being the most prevalent alleles in the population, with a genotypic frequency of 0.55 and 0.38, respectively; HLA-G*III is very rare and HLA-G*IV has a genotypic frequency of 0.07. An evolutive classification of HLA-A alleles results according to their association with either HLA-G*I or HLA-G*II, which does not correlate with the classical serological cross-reacting groups classification. The finding of a strong and selective A/G linkage disequilibria with most HLA-A alleles, together with the existence of less frequent random A/G associations, may suggest that there exist in different haplotypes true and varied A/G genetic distances (and not a recombinational hotspot). It may be inferred from preliminary data that in primates HLA-A/G haplotypes bearing G*II may have appeared later than those bearing G*I.

Alleles↗
PubMed2002

Comparative molecular evolution of primary (Buchnera) and secondary symbionts of aphids based on two protein-coding genes.

A+T content, phylogenetic relationships, codon usage, evolutionary rates, and ratio of synonymous versus non-synonymous substitutions have been studied in partial sequences of the atpD and aroQ/pheA genes of primary ( Buchnera) and secondary symbionts of aphids and a set of selected non-symbiotic bacteria, belonging to the five subdivisions of the Proteobacteria. Compared to the homologous genes of the last group, both genes belonging to Buchnera behave in a similar way, showing a higher A+T content, forming a monophyletic group, a loss in codon bias, especially in third base position, an evolutionary acceleration and an increase in the number of non-synonymous substitutions, confirming previous results reported elsewhere for other genes. When available, these properties have been partly observed with the secondary symbionts, but with values that are intermediate between Buchnera and free living Proteobacteria. They show high A+T content, but not as high as Buchnera, a non-solved phylogenetic position between Buchnera, and the other gamma-Proteobacteria, a loss in codon bias, again not as high as in Buchnera and a significant evolutionary acceleration in the case of the three atpD genes, but not when considering aroQ/pheA genes. These results give support to the hypothesis that they are symbionts at different stages of the symbiotic accommodation to the host.

AT Rich Sequence↗
PubMed1990

Expression in Escherichia coli of ferredoxin:NADP+ reductase from spinach. Bacterial synthesis of the holoflavoprotein and of an active enzyme form lacking the first 28 amino acid residues of the sequence.

A cDNA clone for the preprotein of spinach ferredoxin:NADP+ reductase has been modified to allow the expression in Escherichia coli of the mature flavoprotein form the lacks the transit peptide. An expression vector, pFNR1, was constructed by subcloning the fragment into the plasmid pDS12/RBSII, SphI. In the crude extracts of transformed cells after induction, two active holoproteins of 35 kDa and 32 kDa, respectively, were found. The 32-kDa protein, purified by immunoaffinity chromatography, was found to lack the first 28 residues of the spinach protein sequence and to have a methionine as the N-terminal residue instead of Val29. A new expression plasmid, pFNR2, was obtained by in vitro mutagenesis of the codon GTG for Val29 to the synonymous GTT; in this case, only the 35-kDa protein was expressed by transformed cells. Both the 35-kDa and 32-kDa enzymes were purified and characterized. All the properties analyzed of the cloned 35-kDa enzyme were very similar to those of the spinach flavoprotein. The 32-kDa form showed the same catalytic efficiency of the spinach enzyme as a diaphorase but its interaction with oxidized ferredoxin was partially impaired.

Amino Acid Sequence↗
PubMed2004

Nucleotide sequence variation does not relate to differences in kinetic properties of neutral trehalase from the insect pathogenic fungus Metarhizium anisopliae.

Genetic variability in a putative virulence factor, the neutral trehalase ( Ntl) gene, was examined in strains of the insect pathogenic fungi Metarhizium anisopliae and Metarhizium flavoviride by restriction fragment length polymorphism (RFLP). The Ntl gene was sequenced from four of these strains that showed dissimilar RFLP patterns. Enzyme kinetic experiments were also performed on the partially purified neutral trehalase in order to assess whether nucleotide changes in these strains related to differences in enzyme catalytic function (i.e., Km, Vmax, and Kcat). Finally, the Metarhizium strains were assessed in bioassays against waxworm larvae in order to relate nucleotide variation with Ntl enzyme kinetics and insect virulence. The greatest RFLP variation was observed with Rsa1. M. flavoviride was found to be most dissimilar in RFLP patterns when compared with the M. anisopliae strains. RFLP patterns for Ntl were diagnostic markers for previously studied genetic groups of M. anisopliae. Comparisons of Ntl sequences showed that the introns were found to be more variable (6.2%) than the exons (3.1%). Comparisons of the translated nucleotide codons showed high levels (91%) of synonymous sequence variation between strains. Another fraction of the remaining mutations was neutral, resulting in amino acid substitutions with similar functions. The neutral trehalase was partially purified by preparative isoelectric focus, revealing a single band of enzyme activity as assessed by analytical isoelectric focusing (pI ca. 5). Kinetic properties of the neutral trehalases revealed no differences between the M. anisopliae strains, while the M. flavovoride had a lower Kcat/Km. However, there was lower virulence in one strain that showed Ntl enzyme kinetic properties that were similar to the other strains, suggesting that factors other than neutral trehalase may be responsible for delimiting virulence in this insect pathogenic fungi. Although there is nucleotide variation in genes involved in pathogenicity, this variation is mostly neutral in nature, and there is strong stabilizing selection to maintain enzyme function.

Amino Acid Substitution↗
PubMed1999

The effect of tandem substitutions on the correlation between synonymous and nonsynonymous rates in rodents.

Nonsynonymous substitutions in DNA cause amino acid substitutions while synonymous substitutions in DNA leave amino acids unchanged. The cause of the correlation between the substitution rates at nonsynonymous (K(A)) and synonymous (K(S)) sites in mammals is a contentious issue, and one that impacts on many aspects of molecular evolution. Here we use a large set of orthologous mammalian genes to investigate the causes of the K(A)-K(S) correlation in rodents. The strength of the K(A)-K(S) correlation exceeds the neutral theory expectation when substitution rates are estimated using algorithmic methods, but not when substitution rates are estimated by maximum likelihood. Irrespective of this methodological uncertainty the strength of the K(A)-K(S) correlation appears mostly due to tandem substitutions, an excess of which is generated by substitutional nonindependence. Doublet mutations cannot explain the excess of tandem synonymous-nonsynonymous substitutions, and substitution patterns indicate that selection on silent sites is the likely cause. We find no evidence for selection on codon usage. The nature of the relationship between synonymous divergence and base composition is unclear because we find a significant correlation if we use maximum-likelihood methods but not if we use algorithmic methods. Finally, we find that K(S) is reduced at the start of genes, which suggests that selection for RNA structure may affect silent sites in mammalian protein-coding genes.

Algorithms↗
PubMed2002

Patterns of polymorphism in wheat streak mosaic virus: sequence space explored by a clade of closely related viral genotypes rivals that between the most divergent strains.

Nucleotide (nt) sequence polymorphism within a collection of Wheat streak mosaic virus (WSMV) isolates was examined. An approximately 1267-nt region encompassing the coat protein (CP) cistron and flanking sequences was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for each of 49 isolates not previously sequenced. Consensus sequences were compiled for each isolate based on sequences derived from three clones per RT-PCR product. Among 59 consensus sequences examined, only two were identical. Clades A-C contained divergent isolates from Mexico (Clade A); the Czech Republic, Hungary, and Russia (Clade B); and Iran (Clade C). Fifty-four closely related consensus sequences of isolates from the U.S. (51 sequences), Canada (1 sequence), and Turkey (2 sequences) comprised Clade D. Pair-wise nt divergence between two of the most distantly related sequences (Sidney 81 of Clade D and El Batán 3 of Clade A) was 20%, representing over half of the variable sites (34.1%) in the entire WSMV data set. Maximum pairwise nt divergence within Clade D was 3.6%, yet the proportion of all variable sites within Clade D (21.4%) was similar to that of the Sidney 81-El Batán 3 pair. Patterns of polymorphism within Clade D and the Sidney 81-El Batán 3 pair were remarkably similar with respect to synonymous, nonsynonymous, and noncoding substitutions, as were the proportions of substitutions as a function of nt position within codons. The majority of substitutions within Clade D were synonymous and randomly distributed throughout the coding region examined, whereas nonsynonymous substitutions exhibited a clumped distribution and mostly occurred within the 5'-proximal portion of the CP cistron. Because over half of the polymorphic sites within Clade D were of allele size class 1, the isolates appear to be evolving independently and in a nondeterministic manner, within the constraints of selection. These results indicate that Clade D has undergone substantial and, most likely, recent divergence with the majority of consensus sequence substitutions potentially neutral with respect to fitness. An estimate of evolution rate suggests that the present diversity within the U.S. population arose in about a century, a timeframe corresponding to the establishment of wheat monoculture in the Great Plains.

Base Sequence↗
PubMed2006

Conservation patterns in different functional sequence categories of divergent Drosophila species.

We have explored the distributions of fully conserved ungapped blocks in genome-wide pair-wise alignments of recently completed species of Drosophila: D. melanogaster, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis, and D. mojavensis. Based on these distributions we have found that nearly every functional sequence category possesses its own distinctive conservation pattern, sometimes independent of the overall sequence conservation level. In the coding and regulatory regions, the ungapped blocks were longer than in introns, UTRs, and nonfunctional sequences. At the same time, the blocks in the coding regions carried a 3N + 2 signature characteristic of synonymous substitutions in the third-codon position. Larger block sizes in transcription regulatory regions can be explained by the presence of conserved arrays of binding sites for transcription factors. We also have shown that the longest ungapped blocks, or "ultraconserved" sequences, are associated with specific gene groups, including those encoding ion channels and components of the cytoskeleton. We discuss how restraining conservation patterns may help in mapping functional sequence categories and improve genome annotation.

Animals↗
PubMed2004

Heterogeneous evolution of the Myc-like Anthocyanin regulatory gene and its phylogenetic utility in Cornus L. (Cornaceae).

Anthocyanin is a major pigment in vegetative and floral organs of most plants and plays an important role in plant evolution. The anthocyanin regulatory genes are responsible for regulating transcription of genes in the anthocyanin synthetic pathway. To assess evolutionary significance of sequence variation and evaluate the phylogenetic utility of an anthocyanin regulatory gene, we compared nucleotide sequences of the myc-like anthocyanin regulatory gene in the genus of dogwoods (Cornus: Cornaceae). Phylogenetic analyses demonstrate that the myc-like anthocyanin regulatory gene has potential as an informative phylogenetic marker at different taxonomic levels, depending on the data set considered (DNA or protein sequences) and regions applied (exons or introns). Pairwise nonsynonymous and synonymous substitution rate tests and codon-based substitution models were applied to characterize variation and to identify sites under diversifying selection. Mosaic evolution and heterogeneous rates among different domains and sites were detected.

Anthocyanins↗
PubMed2006

Likelihood-ratio tests for positive selection of human and mouse duplicate genes reveal nonconservative and anomalous properties of widely used methods.

Two commonly used methods based on likelihood-ratio tests (LRTs) for detecting positive Darwinian selection at the molecular level were applied to a data set of 604 gene families containing two members in the human genome and two members in the mouse genome. These methods detected positive selection in a very high proportion of families; in over 50% of families, there was significant evidence of positive selection by one or both methods. However, less than a third of families showing evidence for positive selection by at least one of the methods showed evidence of positive selection by both methods. The outcome of these tests was predicted better by sequence length, G+C content at third-codon positions, and the level of synonymous substitution than by the level of nonsynonymous substitution or the ratio of nonsynonymous to synonymous substitution. These results suggested that LRT-based tests for positive selection may be sensitive to certain factors that make it difficult to reconstruct the true pattern of nucleotide substitution.

Animals↗
PubMed2001

HBe seroconversion and HBs mutation among Japanese hepatitis B virus carriers.

It has been reported in Germany that seroconversion to anti-HBe or anti-HBs is frequently associated with genotype changes of hepatitis B virus (HBV) from genotype A to genotype D. We previously reported that the HBeAg-negative state in Japan was significantly more common in patients infected with genotype B HBV than those infected with genotype C HBV. To determine whether the high prevalence of genotype B in the HBeAg-negative state is due to a change from genotype C to genotype B, 72 pairs of serum samples before and after HBe seroconversion were examined for nucleotide sequences in the S gene (amino acids 42-164) among Japanese HBV carriers. No one was identified to have undergone genotype change during HBe seroconversion. A total of 71 codon mutations were observed. Sixty-two of these 71 codon mutations (87.3%) were non-synonymous. Genotype B HBV had no mutational hot spots. In genotype C, there was a mutational hot spot at amino acid 126 of the S protein, and it was suggested that Thr126 before HBe seroconversion was more susceptible to becoming an asymptomatic carrier after HBe seroconversion than Ile126. In conclusion, genotype changes during HBe seroconversion were not found to be common in Japan.

Journal Article↗
PubMed1998

Methods for the detection of non-random base substitution in virus genes: models of synonymous nucleotide substitution in picornavirus genes.

A substantial fraction of phylogenetic divergence between closely related RNA virus genes is generally accounted for by synonymous (non-amino acid changing) point mutation. Viral evolution may be a complicated phenomena, governed by many different processes. However in this study we ask whether there are any properties in the patterns of synonymous nucleotide substitutions in three different Picornavirus genes that permit the process of accumulation of synonymous point mutation in these genes to be distinguished from some of the simplest most basic evolutionary models. We conclude that while the observed patterns in the occurrence of synonymous point substitution are consistent with those predicted by a model in which base mutation is equi-probable along a gene, and the probability of synonymous substitution determined only by local codon usage, some patterns in the actual nucleotides exchanged remain to be explained.

Amino Acid Substitution↗
PubMed2002

Linkage limits the power of natural selection in Drosophila.

Population genetic theory shows that the efficacy of natural selection is limited by linkage-selection at one site interferes with selection at linked sites. Such interference slows adaptation in asexual genomes and may explain the evolutionary advantage of sex. Here, we test for two signatures of constraint caused by linkage in a sexual genome, by using sequence data from 255 Drosophila melanogaster and Drosophila simulans loci. We find that (i) the rate of protein adaptation is reduced in regions of low recombination, and (ii) evolution at strongly selected amino acid sites interferes with optimal codon usage at weakly selected, tightly linked synonymous sites. Together these findings suggest that linkage limits the rate and degree of adaptation even in recombining genomes.

Adaptation, Physiological↗
PubMed1991

Nucleotide polymorphism and evolution in the glyceraldehyde-3-phosphate dehydrogenase gene (gapA) in natural populations of Salmonella and Escherichia coli.

Nucleotide sequences of the gapA gene, encoding the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, were determined for 16 strains of Salmonella and 13 strains of Escherichia coli recovered from natural populations. Pairs of sequences from strains representing the eight serovar groups of Salmonella differed, on average, at 3.8% of nucleotide sites and 1.1% of inferred amino acids, and comparable values for E. coli were an order of magnitude smaller (0.2% and 0.1%, respectively). The rate of substitution at synonymous sites was significantly higher for codons specifying the catalytic domain of the enzyme than for those encoding the NAD(+)-binding domain, but the nonsynonymous substitution rate showed the opposite relationship. For Salmonella, statistical tests for nonrandom clustering of polymorphic sites failed to provide evidence that intragenic recombination or gene conversion has contributed to the generation of allelic diversity. The topology of a tree constructed from the gapA sequences was generally similar to that of phylogenetic trees of the strains based on multilocus enzyme electrophoresis, but the level of divergence of gapA in Salmonella group V from other Salmonella and E. coli strains is much greater than that indicated by DNA hybridization for the genome as a whole.

Amino Acid Sequence↗
PubMed2006

Sebida: a database for the functional and evolutionary analysis of genes with sex-biased expression.

UNLABELLED: We describe Sebida, a database of genes with sex-biased expression. The database integrates results from multiple, independent microarray studies comparing male and female gene expression in Drosophila melanogaster, Drosophila simulans and Anopheles gambiae. Sebida uses standard nomenclature, which allows individual genes to be compared across different microarray platforms and to be queried by gene name, symbol, or annotation number. In addition to ratios of male/female expression for each gene, Sebida also contains information useful for evolutionary studies, such as local recombination rate, degree of codon bias and interspecific divergence at synonymous and non-synonymous sites. AVAILABILITY: Sebida can be accessed at http://www.sebida.de

Animals↗
PubMed2004

Evolution of prokaryotic DNA: intragenic and extragenic divergences observed with orthologs from three related species.

This study compared orthologous gene pairs from Escherichia coli K12, E. coli O157:H7 EDL933, Salmonella typhimurium LT2, and Yersinia pestis CO92 using only homologs of equal length, and differing nucleotides were counted and mapped. The data showed very clearly how the rates of divergence change with intragenic and extragenic position. The rate of synonymous mutation is lowest near start codons and near stop codons, and, a little surprisingly, the opposite seemed to be true for nonsynonymous substitutions. Analysis outside genes reveals that nucleotide divergences occur less frequently upstream of start codons than downstream of stop codons, and a remarkable drop in divergences is seen for two of the data sets around N = 9 nucleotides upstream of start codons; that is, the Shine-Dalgarno region changes at a lower rate. The explanation is likely to be the link between expressivity and sequence complementarity to the 3' end of 16S ribosomal rRNA. The latter is highly conserved across many bacterial and archaebacterial species.

Bacteria↗