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1

Codon usage in Pseudomonas aeruginosa.  

PubMed Central

We have generated a codon usage table for Pseudomonas aeruginosa. Codon usage in P. aeruginosa is extremely biased. In contrast to E. coli and yeast, P. aeruginosa preferentially uses those codons within a synonymous codon group with the strongest predicted codon-anticodon interaction. We were unable to correlate a particular codon usage pattern with predicted levels of mRNA expressivity. The choice of a third base reflects the high guanine plus cytosine content of the P. aeruginosa genome (67.2%) and cytosine is the preferred nucleotide for the third codon position.

West, S E; Iglewski, B H

1988-01-01

2

Synonymous codon usage in Thermosynechococcus elongatus (cyanobacteria) identifies the factors shaping codon usage variation  

PubMed Central

Analysis of synonymous codon usage pattern in the genome of a thermophilic cyanobacterium, Thermosynechococcus elongatus BP-1 using multivariate statistical analysis revealed a single major explanatory axis accounting for codon usage variation in the organism. This axis is correlated with the GC content at third base of synonymous codons (GC3s) in correspondence analysis taking T. elongatus genes. A negative correlation was observed between effective number of codons i.e. Nc and GC3s. Results suggested a mutational bias as the major factor in shaping codon usage in this cyanobacterium. In comparison to the lowly expressed genes, highly expressed genes of this organism possess significantly higher proportion of pyrimidine-ending codons suggesting that besides, mutational bias, translational selection also influenced codon usage variation in T. elongatus. Correspondence analysis of relative synonymous codon usage (RSCU) with A, T, G, C at third positions (A3s, T3s, G3s, C3s, respectively) also supported this fact and expression levels of genes and gene length also influenced codon usage. A role of translational accuracy was identified in dictating the codon usage variation of this genome. Results indicated that although mutational bias is the major factor in shaping codon usage in T. elongatus, factors like translational selection, translational accuracy and gene expression level also influenced codon usage variation.

Prabha, Ratna; Singh, Dhananjaya P; Gupta, Shailendra K; Farooqi, Samir; Rai, Anil

2012-01-01

3

Codon usage in plant genes.  

PubMed Central

We have examined codon bias in 207 plant gene sequences collected from Genbank and the literature. When this sample was further divided into 53 monocot and 154 dicot genes, the pattern of relative use of synonymous codons was shown to differ between these taxonomic groups, primarily in the use of G + C in the degenerate third base. Maize and soybean codon bias were examined separately and followed the monocot and dicot codon usage patterns respectively. Codon preference in ribulose 1,5 bisphosphate and chlorophyll a/b binding protein, two of the most abundant proteins in leaves was investigated. These highly expressed are more restricted in their codon usage than plant genes in general.

Murray, E E; Lotzer, J; Eberle, M

1989-01-01

4

Codon Usage Domains over Bacterial  

Microsoft Academic Search

The geography of codon bias distributions over prokaryotic genomes and its impact upon chromosomal organization are analyzed. To this aim, we introduce a clustering method based on information theory, specifically designed to cluster genes according to their codon usage and apply it to the coding sequences of Escherichia coli and Bacillus subtilis. One of the clusters identified in each of

Antoine Danchin; Mudassar Iqbal; Matteo Marsili; Massimo Vergassola

5

Analysis of synonymous codon usage patterns in the genus Rhizobium.  

PubMed

The codon usage patterns of rhizobia have received increasing attention. However, little information is available regarding the conserved features of the codon usage patterns in a typical rhizobial genus. The codon usage patterns of six completely sequenced strains belonging to the genus Rhizobium were analysed as model rhizobia in the present study. The relative neutrality plot showed that selection pressure played a role in codon usage in the genus Rhizobium. Spearman's rank correlation analysis combined with correspondence analysis (COA) showed that the codon adaptation index and the effective number of codons (ENC) had strong correlation with the first axis of the COA, which indicated the important role of gene expression level and the ENC in the codon usage patterns in this genus. The relative synonymous codon usage of Cys codons had the strongest correlation with the second axis of the COA. Accordingly, the usage of Cys codons was another important factor that shaped the codon usage patterns in Rhizobium genomes and was a conserved feature of the genus. Moreover, the comparison of codon usage between highly and lowly expressed genes showed that 20 unique preferred codons were shared among Rhizobium genomes, revealing another conserved feature of the genus. This is the first report of the codon usage patterns in the genus Rhizobium. PMID:23653263

Wang, Xinxin; Wu, Liang; Zhou, Ping; Zhu, Shengfeng; An, Wei; Chen, Yu; Zhao, Lin

2013-05-08

6

Codon usage comparison of novel genes in clinical isolates of Haemophilus influenzae  

PubMed Central

A similarity statistic for codon usage was developed and used to compare novel gene sequences found in clinical isolates of Haemophilus influenzae with a reference set of 80 prokaryotic, eukaryotic and viral genomes. These analyses were performed to obtain an indication as to whether individual genes were Haemophilus-like in nature, or if they probably had more recently entered the H.influenzae gene pool via horizontal gene transfer from other species. The average and SD values were calculated for the similarity statistics from a study of the set of all genes in the H.influenzae Rd reference genome that encoded proteins of 100 amino acids or longer. Approximately 80% of Rd genes gave a statistic indicating that they were most like other Rd genes. Genes displaying codon usage statistics >1 SD above this range were either considered part of the highly expressed group of H.influenzae genes, or were considered of foreign origin. An alternative determinant for identifying genes of foreign origin was when the similarity statistics produced a value that was much closer to a non-H.influenzae reference organism than to any of the Haemophilus species contained in the reference set. Approximately 65% of the novel sequences identified in the H.influenzae clinical isolates displayed codon usages most similar to Haemophilus sp. The remaining novel sequences produced similarity statistics closer to one of the other reference genomes thereby suggesting that these sequences may have entered the H.influenzae gene pool more recently via horizontal transfer.

Gladitz, John; Shen, Kai; Antalis, Patricia; Hu, Fen Ze; Post, J. Christopher; Ehrlich, Garth D.

2005-01-01

7

Synonymous codon usage pattern analysis of Hepatitis D virus.  

PubMed

Hepatitis D virus (HDV) is the smallest animal infecting RNA virus with unique features distinguishing it from other Hepatitis viruses. Codon usage variation is considered as an indicator of the forces shaping genome evolution. RSCU (relative synonymous codon usage) values, nucleotide contents, ENC (effective number of codons) values, aromaticity and hydrophobicity of 28 HDV sequences were calculated and compared. RSCU values revealed that most of the codons ended with G or C. A comparative analysis of codon usage between HDV and human cells indicated that the synonymous codon usage pattern of HDV is a mixture of coincidence and antagonism to that of host cell. Finally the characteristics of the synonymous codon usage patterns, ENC plot and the correlation analysis revealed that the most important determinant of the codon usage pattern for HDV is mutational pressure and positive selection force might have some influence in sequence diversity. Comparison of ENC values and GC frequencies at 3rd codon position (GC3s) between HDV and other Hepatitis viruses indicated that HDV comprise a distinct entity. PMID:23352880

Bishal, Arghya Kamal; Mukherjee, Rashmi; Chakraborty, Chandan

2013-01-23

8

Balanced Codon Usage Optimizes Eukaryotic Translational Efficiency  

PubMed Central

Cellular efficiency in protein translation is an important fitness determinant in rapidly growing organisms. It is widely believed that synonymous codons are translated with unequal speeds and that translational efficiency is maximized by the exclusive use of rapidly translated codons. Here we estimate the in vivo translational speeds of all sense codons from the budding yeast Saccharomyces cerevisiae. Surprisingly, preferentially used codons are not translated faster than unpreferred ones. We hypothesize that this phenomenon is a result of codon usage in proportion to cognate tRNA concentrations, the optimal strategy in enhancing translational efficiency under tRNA shortage. Our predicted codon–tRNA balance is indeed observed from all model eukaryotes examined, and its impact on translational efficiency is further validated experimentally. Our study reveals a previously unsuspected mechanism by which unequal codon usage increases translational efficiency, demonstrates widespread natural selection for translational efficiency, and offers new strategies to improve synthetic biology.

Qian, Wenfeng; Yang, Jian-Rong; Pearson, Nathaniel M.; Maclean, Calum; Zhang, Jianzhi

2012-01-01

9

Factors affecting codon usage in Yersinia pestis.  

PubMed

The complete genome of Yersinia pestis which was the causative agent of the systemic invasive infectious disease classically referred as plague, had been recently sequenced. In order to have a further insight into the synonymous codon usage evolution, factors shaping synonymous codon usage pattern of Yersinia pestis were analyzed in this paper. The coding sequences larger than or equal to 300 bp were used in codon usage analysis. Though "G"+"C" content in Y. pestis genome was slightly lower (47.64%), the highly expressed genes tended to use "C" or "G" at synonymous sites compared with lowly expressed genes. Conversely, lowly expressed genes tended to prefer "A" or "T" at synonymous positions. Gene expression level was strongly correlated with the first axis of the correspondence analysis (COA) (R=0.63, P<0.0001). By the analyses of the codon usage pattern of highly and lowly expressed genes, it was confirmed that gene expression level was partially responsible for the codon usage bias. GC-skew analysis showed that codon usage suffered replication-transcriptional selection. Codon adaptation index (CAI), frequency of "C"+"G" at the synonymous third position of codon (GC3s) and the effective number of codons (Nc) values showed some differences among different gene length groups. "G"+"C" content of genes was strongly correlated with the first axis of the COA (R=0.72, P<0.0001). It could be concluded that gene expressivity, replication-transcriptional selection, gene length and gene composition constraints were the main affecting factors of codon usage variation in Y. pestis. PMID:12796821

Hou, Zhuo-Cheng; Yang, Ning

2003-06-01

10

Universal function-specificity of codon usage  

PubMed Central

Synonymous codon usage has long been known as a factor that affects average expression level of proteins in fast-growing microorganisms, but neither its role in dynamic changes of expression in response to environmental changes nor selective factors shaping it in the genomes of higher eukaryotes have been fully understood. Here, we propose that codon usage is ubiquitously selected to synchronize the translation efficiency with the dynamic alteration of protein expression in response to environmental and physiological changes. Our analysis reveals that codon usage is universally correlated with gene function, suggesting its potential contribution to synchronized regulation of genes with similar functions. We directly show that coexpressed genes have similar synonymous codon usages within the genomes of human, yeast, Caenorhabditis elegans and Escherichia coli. We also demonstrate that perturbing the codon usage directly affects the level or even direction of changes in protein expression in response to environmental stimuli. Perturbing tRNA composition also has tangible phenotypic effects on the cell. By showing that codon usage is universally function-specific, our results expand, to almost all organisms, the notion that cells may need to dynamically alter their intracellular tRNA composition in order to adapt to their new environment or physiological role.

Najafabadi, Hamed Shateri; Goodarzi, Hani; Salavati, Reza

2009-01-01

11

Trends in the codon usage patterns of Chromohalobacter salexigens genes  

PubMed Central

Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for growth. In order to reveal the factors influencing architecture of protein coding genes in C. salexigens, pattern of synonymous codon usage bias has been investigated. Overall codon usage analysis of the microorganism revealed that C and G ending codons are predominantly used in all the genes which are indicative of mutational bias. Multivariate statistical analysis showed that the genes are separated along the first major explanatory axis according to their expression levels and their genomic GC content at the synonymous third positions of the codons. Both NC plot and correspondence analysis on Relative Synonymous Codon Usage (RSCU) indicates that the variation in codon usage among the genes may be due to mutational bias at the DNA level and natural selection acting at the level of mRNA translation. Gene length and the hydrophobicity of the encoded protein also influence the codon usage variation of genes to some extent. A comparison of the relative synonymous codon usage between 10% each of highly and lowly expressed genes determines 23 optimal codons, which are statistically over represented in the former group of genes and may provide useful information for salt-stressed gene prediction and gene-transformation. Furthermore, genes for regulatory functions; mobile and extrachromosomal element functions; and cell envelope are observed to be highly expressed. The study could provide insight into the gene expression response of halophilic bacteria and facilitate establishment of effective strategies to develop salt-tolerant crops of agronomic value.

Sanjukta, Rajkumari; Farooqi, Mohammad Samir; Sharma, Naveen; Rai, Anil; Mishra, Dwijesh Chandra; Singh, Dhananjaya P

2012-01-01

12

Codon Usage and Selection on Proteins  

Microsoft Academic Search

Selection pressures on proteins are usually measured by comparing homologous nucleotide sequences (Zuckerkandl and Pauling 1965). Recently we introduced a novel method, termed volatility, to estimate selection pressures on proteins on the basis of their synonymous codon usage (Plotkin and Dushoff 2003; Plotkin et al. 2004). Here we provide a theoretical foundation for this approach. Under the Fisher-Wright model, we

Joshua B. Plotkin; Jonathan Dushoff; Michael M. Desai; Hunter B. Fraser

2006-01-01

13

Low-usage codons and rare codons of Escherichia coli Mini Review  

Microsoft Academic Search

Summary In Escherichia coli (E. coli), a low-usage codon is defined as a codon that is used rarely or infrequently in the genome with usage frequency lower than the smallest value (or frequency cut-off) among the usage frequencies of non-degenerate codons (Met codon AUG and Trp codon UGG) and the optimal codons for amino acids Leu, Ile, Val, Ser, Pro,

Dequan Chen; Donald E. Texada

14

Characterization of Codon usage bias in the newly identified DEV UL18 gene  

NASA Astrophysics Data System (ADS)

In this study, Codon usage bias (CUB) of DEV UL18 gene was analyzed, the results showed that codon usage bias in the DEV UL18 gene was strong bias towards the synonymous codons with A and T at the third codon position. Phylogenetic tree based on the amino acid sequences of the DEV UL18 gene and the 27 other herpesviruses revealed that UL18 gene of the DEV CHv strain and some fowl herpesviruses such as MeHV-1, GaHV-2 and GaHV-3 were clustered within a monophyletic clade and grouped within alphaherpesvirinae. The ENC-GC3S plot indicated that codon usage bias has strong species-specificity between DEV and 27 reference herpesviruses, and suggests that factors other than gene composition, such as translational selection leading to the codon usage variation among genes in different organisms, contribute to the codon usage among the different herpesviruses. Comparison of codon preferences of DEV UL18 gene with those of E. coli , yeast and humans showed that there were 20 codons showing distinct usage differences between DEV UL18 and yeast, 22 between DEV UL18 and humans, 23 between DEV UL18 and E.coli, which indicated the codon usage bias pattern in the DEV UL18 gene was similar to that of yeast. It is infered that the yeast expression system may be more suitable for the DEV UL18 expression.

Chen, Xiwen; Cheng, Anchun; Wang, Mingshu; Xiang, Jun

2011-10-01

15

P-value based visualization of codon usage data  

Microsoft Academic Search

Two important and not yet solved problems in bacterial genome research are the identification of horizontally transferred genes and the prediction of gene expression levels. Both problems can be addressed by multivariate analysis of codon usage data. In particular dimensionality reduction methods for visualization of multivariate data have shown to be effective tools for codon usage analysis. We here propose

Peter Meinicke; Thomas Brodag; Wolfgang Florian Fricke; Stephan Waack

2006-01-01

16

Measure of synonymous codon usage diversity among genes in bacteria  

Microsoft Academic Search

BACKGROUND: In many bacteria, intragenomic diversity in synonymous codon usage among genes has been reported. However, no quantitative attempt has been made to compare the diversity levels among different genomes. Here, we introduce a mean dissimilarity-based index (Dmean) for quantifying the level of diversity in synonymous codon usage among all genes within a genome. RESULTS: The application of Dmean to

Haruo Suzuki; Rintaro Saito; Masaru Tomita

2009-01-01

17

Analysis of Synonymous Codon Usage Bias in Chlamydia  

Microsoft Academic Search

Abstract , Chlamydiae,are obligate intracellular bacterial pathogens that cause ocular and sexually transmitted diseases, and are associated with cardiovascular diseases. The analysis of codon usage may improve our understanding of the evolution and pathogenesis of Chlamydiaand allow reengineering of target genes to improve their expression for gene therapy. Here, we analyzed the codon usage of C. muridarum, C. trachomatis(here indicating

H. Lu; Wei-ming Zhao; Yan Zheng; Hong Wang; Mei Qi; Xiu-ping Yu

2005-01-01

18

Codon usage in Entamoeba histolytica, E. dispar and E. invadens  

Microsoft Academic Search

We analyzed the frequencies of genetic codon usage of 68 non-redundant protein coding genes from the human-pathogenic E. histolytica (28 117 codons), 6 from the non-pathogenic E. dispar (1744 codons), and 4 from the reptilian E. invadens (933 codons). The A + U contents of the protein coding sequences from E. histolytica, E. dispar, and E. invadens were 67%, 66%,

Tomoyoshi Nozaki; Takashi Asai; Tsutomu Takeuchi

1997-01-01

19

Selective pressure dominates the synonymous codon usage in parvoviridae.  

PubMed

Parvoviridae is a family of small non-enveloped viruses and divided into two subfamilies. The family members infect a wide range of organisms from insects to humans and some of the members (e.g., nonpathogenic adeno-associated viruses) are effective gene therapy delivery vectors. We detailed the synonymous codon usage pattern of Parvoviridae family from the available 58 sequenced genomes through multivariate statistical methods. Our results revealed that nine viruses showed some degree of strong codon bias, and the others possessed a general weak trend of codon bias. ENc-plot and neutrality plot results showed that selective pressure dominated over mutation in shapes coding sequence's composition. The overall GC content and GC content at the third synonymous codon position were the principal determinants behind the variations within the codon usage patterns, as they both significantly correlated with the first axis of correspondence analysis. In addition, gene length had no direct influence on the codon usage pattern. Densovirinae subfamily and Parvovirinae subfamily possessed nine identical preferred codons, though most of the two subfamilies codon usage frequencies were significantly different. The result of cluster analysis based on synonymous codon usage was discordant with that of taxonomic classification. Adeno-associated viruses formed a separated clade far from other Parvoviridae members in the dendrogram. Thus, we concluded that natural selection rather than mutation pressure accounts for the main factor that affects the codon bias in Parvoviridae family. PMID:22996735

Shi, Sheng-Lin; Jiang, Yi-Ren; Liu, Yan-Qun; Xia, Run-Xi; Qin, Li

2012-09-21

20

Trends in Codon and Amino Acid Usage in Thermotoga maritima  

Microsoft Academic Search

.   The usage of synonymous codons and the frequencies of amino acids were investigated in the complete genome of the bacterium\\u000a Thermotoga maritima using a multivariate statistical approach. The GC3 content of each gene was the most prominent source of variation of codon\\u000a usage. Surprisingly the usage of UGU and UGC (synonymous triplets coding for Cys, the least frequent amino

Alejandro Zavala; Hugo Naya; Héctor Romero; Héctor Musto

2002-01-01

21

Impact of translational selection on codon usage bias in the archaeon Methanococcus maripaludis  

PubMed Central

Patterns of codon usage have been extensively studied among Bacteria and Eukaryotes, but there has been little investigation of species from the third domain of life, the Archaea. Here, we examine the nature of codon usage bias in a methanogenic archaeon, Methanococcus maripaludis. Genome-wide patterns of codon usage are dominated by a strong A + T bias, presumably largely reflecting mutation patterns. Nevertheless, there is variation among genes in the use of a subset of putatively translationally optimal codons, which is strongly correlated with gene expression level. In comparison with Bacteria such as Escherichia coli, the strength of selected codon usage bias in highly expressed genes in M. maripaludis seems surprisingly high given its moderate growth rate. However, the pattern of selected codon usage differs between M. maripaludis and E. coli: in the archaeon, strongly selected codon usage bias is largely restricted to twofold degenerate amino acids (AAs). Weaker bias among the codons for fourfold degenerate AAs is consistent with the small number of tRNA genes in the M. maripaludis genome.

Emery, Laura R.; Sharp, Paul M.

2011-01-01

22

Gender-specific selection on codon usage in plant genomes  

PubMed Central

Background Currently, there is little data available regarding the role of gender-specific gene expression on synonymous codon usage (translational selection) in most organisms, and particularly plants. Using gender-specific EST libraries (with > 4000 ESTs) from Zea mays and Triticum aestivum, we assessed whether gender-specific gene expression per se and gender-specific gene expression level are associated with selection on codon usage. Results We found clear evidence of a greater bias in codon usage for genes expressed in female than in male organs and gametes, based on the variation in GC content at third codon positions and the frequency of species-preferred codons. This finding holds true for both highly and for lowly expressed genes. In addition, we found that highly expressed genes have greater codon bias than lowly expressed genes for both female- and male-specific genes. Moreover, in both species, genes with female-specific expression show a greater usage of species-specific preferred codons for each of the 18 amino acids having synonymous codons. A supplemental analysis of Brassica napus suggests that bias in codon usage could also be higher in genes expressed in male gametophytic tissues than in heterogeneous (flower) tissues. Conclusion This study reports gender-specific bias in codon usage in plants. The findings reported here, based on the analysis of 1 497 876 codons, are not caused either by differences in the biological functions of the genes or by differences in protein lengths, nor are they likely attributable to mutational bias. The data are best explained by gender-specific translational selection. Plausible explanations for these findings and the relevance to these and other organisms are discussed.

2007-01-01

23

Selected codon usage bias in members of the class Mollicutes.  

PubMed

Mollicutes are parasitic microorganisms mainly characterized by small cell sizes, reduced genomes and great A and T mutational bias. We analyzed the codon usage patterns of the completely sequenced genomes of bacteria that belong to this class. We found that for many organisms not only mutational bias but also selection has a major effect on codon usage. Through a comparative perspective and based on three widely used criteria we were able to classify Mollicutes according to the effect of selection on codon usage. We found conserved optimal codons in many species and study the tRNA gene pool in each genome. Previous results are reinforced by the fact that, when selection is operative, the putative optimal codons found match the respective cognate tRNA. Finally, we trace selection effect backwards to the common ancestor of the class and estimate the phylogenetic inertia associated with this character. We discuss the possible scenarios that explain the observed evolutionary patterns. PMID:21147204

Iriarte, Andrés; Baraibar, Juan Diego; Romero, Héctor; Musto, Héctor

2010-12-13

24

Selection, Mutations and Codon Usage in Bacterial Model  

Microsoft Academic Search

We present a statistical model of bacterial evolution based on the coupling between codon usage and tRNA abundance. Such a model interprets this aspect of the evolutionary process as a balance between the codon homogenization effect due to mutation process and the improvement of the translation phase due to natural selection. We develop a thermodynamical description of the asymptotic state

Franco Bagnoli; Pietro Lio

1998-01-01

25

Selection, mutations and codon usage in a bacterial model  

Microsoft Academic Search

We present a statistical model of bacterial evolution based on the coupling between codon usage and tRNA abundance. Such a model interprets this aspect of the evolutionary process as a balance between the codon homogenization effect due to mutation process and the improvement of the translation phase due to natural selection. We develop a thermodynamical description of the asymptotic state

Franco Bagnoli

1995-01-01

26

Synonymous codon usage in chloroplast genome of Coffea arabica  

PubMed Central

Synonymous codon usage of 53 protein coding genes in chloroplast genome of Coffea arabica was analyzed for the first time to find out the possible factors contributing codon bias. All preferred synonymous codons were found to use A/T ending codons as chloroplast genomes are rich in AT. No difference in preference for preferred codons was observed in any of the two strands, viz., leading and lagging strands. Complex correlations between total base compositions (A, T, G, C, GC) and silent base contents (A3, T3, G3, C3, GC3) revealed that compositional constraints played crucial role in shaping the codon usage pattern of C. arabica chloroplast genome. ENC Vs GC3 plot grouped majority of the analyzed genes on or just below the left side of the expected GC3 curve indicating the influence of base compositional constraints in regulating codon usage. But some of the genes lie distantly below the continuous curve confirmed the influence of some other factors on the codon usage across those genes. Influence of compositional constraints was further confirmed by correspondence analysis as axis 1 and 3 had significant correlations with silent base contents. Correlation of ENC with axis 1, 4 and CAI with 1, 2 prognosticated the minor influence of selection in nature but exact separation of highly and lowly expressed genes could not be seen. From the present study, we concluded that mutational pressure combined with weak selection influenced the pattern of synonymous codon usage across the genes in the chloroplast genomes of C. arabica.

Nair, Rahul R; Nandhini, Manivasagam B; Monalisha, Elango; Murugan, Kavitha; Sethuraman, Thilaga; Nagarajan, Sangeetha; Rao, Nayani Surya Prakash; Ganesh, Doss

2012-01-01

27

Synonymous codon usage in chloroplast genome of Coffea arabica.  

PubMed

Synonymous codon usage of 53 protein coding genes in chloroplast genome of Coffea arabica was analyzed for the first time to find out the possible factors contributing codon bias. All preferred synonymous codons were found to use A/T ending codons as chloroplast genomes are rich in AT. No difference in preference for preferred codons was observed in any of the two strands, viz., leading and lagging strands. Complex correlations between total base compositions (A, T, G, C, GC) and silent base contents (A(3), T(3), G(3), C(3), GC(3)) revealed that compositional constraints played crucial role in shaping the codon usage pattern of C. arabica chloroplast genome. ENC Vs GC(3) plot grouped majority of the analyzed genes on or just below the left side of the expected GC(3) curve indicating the influence of base compositional constraints in regulating codon usage. But some of the genes lie distantly below the continuous curve confirmed the influence of some other factors on the codon usage across those genes. Influence of compositional constraints was further confirmed by correspondence analysis as axis 1 and 3 had significant correlations with silent base contents. Correlation of ENC with axis 1, 4 and CAI with 1, 2 prognosticated the minor influence of selection in nature but exact separation of highly and lowly expressed genes could not be seen. From the present study, we concluded that mutational pressure combined with weak selection influenced the pattern of synonymous codon usage across the genes in the chloroplast genomes of C. arabica. PMID:23251044

Nair, Rahul R; Nandhini, Manivasagam B; Monalisha, Elango; Murugan, Kavitha; Sethuraman, Thilaga; Nagarajan, Sangeetha; Rao, Nayani Surya Prakash; Ganesh, Doss

2012-11-13

28

INCA: synonymous codon usage analysis and clustering by means of self-organizing map  

Microsoft Academic Search

Summary: INteractive Codon usage Analysis (INCA) provides an array of features useful in analysis of synonymous codon usage in whole genomes. In addition to computing codon fre- quencies and several usage indices, such as 'codon bias', effective Nc and CAI, the primary strength of INCA has numer- ous options for the interactive graphical display of calculated values, thus allowing visual

Fran Supek; Kristian Vlahovicek

2004-01-01

29

Relationships Among Stop Codon Usage Bias, Its Context, Isochores, and Gene Expression Level in Various Eukaryotes  

Microsoft Academic Search

It is well known that stop codons play a critical role in the process of protein synthesis. However, little effort has been made to investigate whether stop codon usage exhibits biases, such as widely seen for synonymous codon usage. Here we systematically investigate stop codon usage bias in various eukaryotes as well as its relationships with its context, GC3 content,

Jingchun Sun; Ming Chen; Jinlin Xu; Jianhua Luo

2005-01-01

30

The usage of codons which are similar to stop codons in the genomes of Xylella fastidiosa and Xanthomonas citri.  

PubMed

During the evolution of living organisms, a natural selection event occurs toward the optimization of their genomes regarding the usage of codons. During this process which is known as codon bias, a set of preferred codons is naturally defined in the genome of a given organism, since there are 61 possible codons (plus 3 stop codons) to 20 amino acids. Such event leads to optimization of metabolic cellular processes such as translational efficiency, RNA stability and energy saving. Although we know why, we do not know how exactly a set of preferred codons for each amino acid is defined for a given genome considering that the usage frequency of each synonymous codons is peculiar to each organism. In order to help answering this question, we analyzed the usage frequency of codons which are similar to stop codons, since a minor mutation on these codons may lead to a stop codon into the open reading frame compromising the protein expression as a result. We found a reduced use of those codons in Xanthomomas axonopodis pv. citri which presents an optimized genome regarding codon usage. On the other hand, such codons are more often used in Xylella fastidiosa, which does not seem to have established codon preferences as previously shown. Our results support that a set of preferred codons is not randomly selected and propose new ideas to the field warranting further experiments in this regard. PMID:21046398

Galves-dos-Santos, Dilermando P; Martins-de-Souza, Daniel

2010-11-04

31

Synonymous codon usage in Zea mays L. nuclear genes is varied by levels of C and G-ending codons.  

PubMed Central

A multivariate statistical method called correspondence analysis was used to examine the codon usage of one-hundred-and-one nuclear genes of maize (Zea mays L.). Forty percent of the variation in codon usage was due to bias toward G or C-ending versus A or U-ending codons. Differences in levels of G-ending codons showed the weakest correlation with the major codon usage bias. The bias toward C or U versus A or G in the silent third nucleotide position of synonymous codons accounted for approximately 10% of the variation in codon usage. The G+C content of the silent third nucleotide position of coding regions was not strongly correlated with G+C content of introns. Codon usage was strongly biased toward codons ending in G or C for a number of highly expressed genes including most light-regulated chloroplast proteins, ABA-induced proteins, histones, and anthocyanin biosynthetic enzymes. Codon usage of genes encoding storage proteins and regulatory proteins, such as transposases, kinases, phosphatases and transcription factors, was more random than that of genes encoding cytosolic enzymes with similar bias toward G or C-ending codons. Codon usage in maize may reflect both regional bias on nucleotide composition and selection on the silent third nucleotide position.

Fennoy, S L; Bailey-Serres, J

1993-01-01

32

Translational selection on codon usage in the genus Aspergillus.  

PubMed

Aspergillus is a genus of mold fungi that includes more than 200 described species. Many members of the group are relevant pathogens and other species are economically important. Only one species has been analyzed for codon usage, and this was performed with a small number of genes. In this paper, we report the codon usage patterns of eight completely sequenced genomes which belong to this genus. The results suggest that selection for translational efficiency and accuracy are the major factors shaping codon usage in all of the species studied so far, and therefore they were active in the last common ancestor of the group. Composition and molecular distances analyses show that highly expressed genes evolve slower at synonymous sites. We identified a conserved core of translationally optimal codons and study the tRNA gene pool in each genome. We found that the great majority of preferred triplets match the respective cognate tRNA with more copies in the respective genome. We discuss the possible scenarios that can explain the observed differences among the species analyzed. Finally we highlight the biotechnological application of this research regarding heterologous protein expression. PMID:22742978

Iriarte, Andrés; Sanguinetti, Manuel; Fernández-Calero, Tamara; Naya, Hugo; Ramón, Ana; Musto, Héctor

2012-06-26

33

Estimating selection on synonymous codon usage from noisy experimental data.  

PubMed

A key goal in molecular evolution is to extract mechanistic insights from signatures of selection. A case study is codon usage, where despite many recent advances and hypotheses, two longstanding problems remain: the relative contribution of selection and mutation in determining codon frequencies and the relative contribution of translational speed and accuracy to selection. The relevant targets of selection--the rate of translation and of mistranslation of a codon per unit time in the cell--can only be related to mechanistic properties of the translational apparatus if the number of transcripts per cell is known, requiring use of gene expression measurements. Perhaps surprisingly, different gene-expression data sets yield markedly different estimates of selection. We show that this is largely due to measurement noise, notably due to differences between studies rather than instrument error or biological variability. We develop an analytical framework that explicitly models noise in expression in the context of the population-genetic model. Estimates of mutation and selection strength in budding yeast produced by this method are robust to the expression data set used and are substantially higher than estimates using a noise-blind approach. We introduce per-gene selection estimates that correlate well with previous scoring systems, such as the codon adaptation index, while now carrying an evolutionary interpretation. On average, selection for codon usage in budding yeast is weak, yet our estimates show that genes range from virtually unselected to average per-codon selection coefficients above the inverse population size. Our analytical framework may be generally useful for distinguishing biological signals from measurement noise in other applications that depend upon measurements of gene expression. PMID:23493257

Wallace, Edward W J; Airoldi, Edoardo M; Drummond, D Allan

2013-03-14

34

The extent of codon usage bias in human RNA viruses and its evolutionary origin  

Microsoft Academic Search

Revealing the determinants of codon usage bias is central to the understanding of factors governing viral evolution. Herein, we report the results of a survey of codon usage bias in a wide range of genetically and ecologically diverse human RNA viruses. This analysis showed that the overall extent of codon usage bias in RNA viruses is low and that there

Gareth M Jenkins; Edward C Holmes

2003-01-01

35

Can simple codon pair usage predict protein-protein interaction?  

PubMed

Deciphering functional interactions between proteins is one of the great challenges in biology. Sequence-based homology-free encoding schemes have been increasingly applied to develop promising protein-protein interaction (PPI) predictors by means of statistical or machine learning methods. Here we analyze the relationship between codon pair usage and PPIs in yeast. We show that codon pair usage of interacting protein pairs differs significantly from randomly expected. This motivates the development of a novel approach for predicting PPIs, with codon pair frequency difference as input to a Support Vector Machine predictor, termed as CCPPI. 10-fold cross-validation tests based on yeast PPI datasets with balanced positive-to-negative ratios indicate that CCPPI performs better than other sequence-based encoding schemes. Moreover, it ranks the best when tested on an unbalanced large-scale dataset. Although CCPPI is subjected to high false positive rates like many PPI predictors, statistical analyses of the predicted true positives confirm that the success of CCPPI is partly ascribed to its capability to capture proteomic co-expression and functional similarities between interacting protein pairs. Our findings suggest that codon pairs of interacting protein pairs evolve in a coordinated manner and consequently they provide additional information beyond amino acids-based encoding schemes. CCPPI has been made freely available at: http://protein.cau.edu.cn/ccppi. PMID:22392100

Zhou, Yuan; Zhou, Ying-Si; He, Fei; Song, Jiangning; Zhang, Ziding

2012-03-05

36

Codon usage patterns among genes for lepidopteran hemolymph proteins  

Microsoft Academic Search

Patterns in codon usage were examined for the coding regions of the 23 known lepidopteran hemolymph proteins. Coding triplets\\u000a are GC rich at the third position and a significant linear relationship between GC content of silent and nonsilent (replacement)\\u000a sites was demonstrated. Intron GC content was significantly lower than in coding regions and no relationship between intron\\u000a GC content and

Donald R. Frohlich; Michael A. Wells

1994-01-01

37

Developmental Stage and Level of Codon Usage Bias in Drosophila  

PubMed Central

Codon usage bias (CUB) is a ubiquitous observation in molecular evolution. As a model, Drosophila has been particularly well-studied and indications show that selection at least partially controls codon usage, probably through selection for translational efficiency. Although many aspects of Drosophila CUB have been studied, this is the first study relating codon usage to development in this holometabolous insect with very different life stages. Here we ask the question: What developmental stage of Drosophila melanogaster has the greatest CUB? Genes with maximum expression in the larval stage have the greatest overall CUB when compared with embryos, pupae, and adults. (The same pattern was observed in Drosophila pseudoobscura, see Supplementary Material online.) We hypothesize this is related to the very rapid growth of larvae, placing increased selective pressure to produce large amounts of protein: a 300-fold increase requiring an approximate doubling of protein content every 10 h. Genes with highest expression in adult males and early embryos, stages with the least de novo protein synthesis, display the least CUB. These results are consistent with the hypothesis that CUB is caused (at least in part) by selection for efficient protein production. This seems to hold on the individual gene level (highly expressed genes are more biased than lowly expressed genes) as well as on a more global scale where genes with maximum expression during times of very rapid growth and protein synthesis are more biased than genes with maximum expression during times of low growth.

Mason, Christopher E.; White, Kevin P.; Powell, Jeffrey R.

2008-01-01

38

Codon usage bias in prokaryotic pyrimidine-ending codons is associated with the degeneracy of the encoded amino acids  

PubMed Central

Synonymous codons are unevenly distributed among genes, a phenomenon termed codon usage bias. Understanding the patterns of codon bias and the forces shaping them is a major step towards elucidating the adaptive advantage codon choice can confer at the level of individual genes and organisms. Here, we perform a large-scale analysis to assess codon usage bias pattern of pyrimidine-ending codons in highly expressed genes in prokaryotes. We find a bias pattern linked to the degeneracy of the encoded amino acid. Specifically, we show that codon-pairs that encode two- and three-fold degenerate amino acids are biased towards the C-ending codon while codons encoding four-fold degenerate amino acids are biased towards the U-ending codon. This codon usage pattern is widespread in prokaryotes, and its strength is correlated with translational selection both within and between organisms. We show that this bias is associated with an improved correspondence with the tRNA pool, avoidance of mis-incorporation errors during translation and moderate stability of codon–anticodon interaction, all consistent with more efficient translation.

Wald, Naama; Alroy, Maya; Botzman, Maya; Margalit, Hanah

2012-01-01

39

Gene expression level influences amino acid usage, but not codon usage, in the tsetse fly endosymbiont Wigglesworthia  

Microsoft Academic Search

Wigglesworthia glossinidia brevipalpis, the obligate bacterial endosymbiont of the tsetse fly Glossinabrevipalpis,ischaracterizedbyextremegenomereductionandATnucleotidecomposition bias. Here, multivariate statistical analyses are used to test the hypothesis that mutational bias and genetic drift shape synonymous codon usage and amino acid usage of Wigglesworthia. The results show that synonymous codon usage patterns vary little across the genome and do not distinguish genes of putative high

J. T. Herbeck

2003-01-01

40

Codon Usage and tRNA Genes in Eukaryotes: Correlation of Codon Usage Diversity with Translation Efficiency and with CG-Dinucleotide Usage as Assessed by Multivariate Analysis  

Microsoft Academic Search

.   The species-specific diversity of codon usage in five eukaryotes (Schizosaccharomyces pombe, Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis, and Homo sapiens) was investigated with principal component analysis. Optimal codons for translation were predicted on the basis of tRNA-gene\\u000a copy numbers. Highly expressed genes, such as those encoding ribosomal proteins and histones in S. pombe, C. elegans, and D. melanogaster, have

Shigehiko Kanaya; Yuko Yamada; Makoto Kinouchi; Yoshihiro Kudo; Toshimichi Ikemura

2001-01-01

41

Variation in global codon usage bias among prokaryotic organisms is associated with their lifestyles  

PubMed Central

Background It is widely acknowledged that synonymous codons are used unevenly among genes in a genome. In organisms under translational selection, genes encoding highly expressed proteins are enriched with specific codons. This phenomenon, termed codon usage bias, is common to many organisms and has been recognized as influencing cellular fitness. This suggests that the global extent of codon usage bias of an organism might be associated with its phenotypic traits. Results To test this hypothesis we used a simple measure for assessing the extent of codon bias of an organism, and applied it to hundreds of sequenced prokaryotes. Our analysis revealed a large variability in this measure: there are organisms showing very high degrees of codon usage bias and organisms exhibiting almost no differential use of synonymous codons among different genes. Remarkably, we found that the extent of codon usage bias corresponds to the lifestyle of the organism. Especially, organisms able to live in a wide range of habitats exhibit high extents of codon usage bias, consistent with their need to adapt efficiently to different environments. Pathogenic prokaryotes also demonstrate higher extents of codon usage bias than non-pathogenic prokaryotes, in accord with the multiple environments that many pathogens occupy. Our results show that the previously observed correlation between growth rate and metabolic variability is attributed to their individual associations with codon usage bias. Conclusions Our results suggest that the extent of codon usage bias of an organism plays a role in the adaptation of prokaryotes to their environments.

2011-01-01

42

Comparative studies on codon usage pattern of chloroplasts and their host nuclear genes in four plant species  

Microsoft Academic Search

A detailed comparison was made of codon usage of chloroplast genes with their host (nuclear) genes in the four angiosperm\\u000a speciesOryza sativa, Zea mays, Triticum aestivum andArabidopsis thaliana. The average GC content of the entire genes, and at the three codon positions individually, was higher in nuclear than in\\u000a chloroplast genes, suggesting different genomic organization and mutation pressures in nuclear

Qingpo Liu; Qingzhong Xue

2005-01-01

43

Impact of bias discrepancy and amino acid usage on estimates of the effective number of codons used in a gene, and a test for selection on codon usage  

Microsoft Academic Search

The effective number of codons (Nc) used in a gene is one of the most commonly used measures of synonymous codon usage bias, owing much of its popularity to the fact that it is species independent and that simulation studies have shown that it is less dependent of gene length than other measures. In this paper I provide a clear

Anders Fuglsang

2008-01-01

44

Evolutionary Patterns of Codon Usage in the Chloroplast Gene rbc L  

Microsoft Academic Search

In this study we reconstruct the evolution of codon usage bias in the chloroplast gene rbcL using a phylogeny of 92 green-plant taxa. We employ a measure of codon usage bias that accounts for chloroplast genomic nucleotide content, as an attempt to limit plausible explanations for patterns of codon bias evolution to selection- or drift-based processes. This measure uses maximum

Dennis P. Wall; Joshua T. Herbeck

2003-01-01

45

Evolutionary Patterns of Codon Usage in the Chloroplast Gene rbc L  

Microsoft Academic Search

In this study we reconstruct the evolution of codon usage bias in the chloroplast gene rbcL us- ing a phylogeny of 92 green-plant taxa. We employ a measure of codon usage bias that accounts for chlo- roplast genomic nucleotide content, as an attempt to limit plausible explanations for patterns of codon bias evolution to selection- or drift-based processes. This measure

Dennis P. Wall; Joshua T. Herbeck

2003-01-01

46

Analysis of Synonymous Codon Usage Patterns in Seven Different Citrus Species  

PubMed Central

We used large samples of expressed sequence tags to characterize the patterns of codon usage bias (CUB) in seven different Citrus species and to analyze their evolutionary effect on selection and base composition. We found that A- and T-ending codons are predominant in Citrus species. Next, we identified 21 codons for 18 different amino acids that were considered preferred codons in all seven species. We then performed correspondence analysis and constructed plots for the effective number of codons (ENCs) to analyze synonymous codon usage. Multiple regression analysis showed that gene expression in each species had a constant influence on the frequency of optional codons (FOP). Base composition differences between the proportions were large. Finally, positive selection was detected during the evolutionary process of the different Citrus species. Overall, our results suggest that codon usages were the result of positive selection. Codon usage variation among Citrus genes is influenced by translational selection, mutational bias, and gene length. CUB is strongly affected by selection pressure at the translational level, and gene length plays only a minor role. One possible explanation for this is that the selection-mediated codon bias is consistently strong in Citrus, which is one of the most widely cultivated fruit trees.

Xu, Chen; Dong, Jing; Tong, Chunfa; Gong, Xindong; Wen, Qiang; Zhuge, Qiang

2013-01-01

47

Characterizing the native codon usages of a genome: an axis projection approach.  

PubMed

Codon usage can provide insights into the nature of the genes in a genome. Genes that are "native" to a genome (have not been recently acquired by horizontal transfer) range in codon usage from a low-bias "typical" usage to a more biased "high-expression" usage characteristic of genes encoding abundant proteins. Genes that differ from these native codon usages are candidates for foreign genes that have been recently acquired by horizontal gene transfer. In this study, we present a method for characterizing the codon usages of native genes--both typical and highly expressed--within a genome. Each gene is evaluated relative to a half line (or axis) in a 59D space of codon usage. The axis begins at the modal codon usage, the usage that matches the largest number of genes in the genome, and it passes through a point representing the codon usage of a set of genes with expression-related bias. A gene whose codon usage matches (does not significantly differ from) a point on this axis is a candidate native gene, and the location of its projection onto the axis provides a general estimate of its expression level. A gene that differs significantly from all points on the axis is a candidate foreign gene. This automated approach offers significant improvements over existing methods. We illustrate this by analyzing the genomes of Pseudomonas aeruginosa PAO1 and Bacillus anthracis A0248, which can be difficult to analyze with commonly used methods due to their biased base compositions. Finally, we use this approach to measure the proportion of candidate foreign genes in 923 bacterial and archaeal genomes. The organisms with the most homogeneous genomes (containing the fewest candidate foreign genes) are mostly endosymbionts and parasites, though with exceptions that include Pelagibacter ubique and Beutenbergia cavernae. The organisms with the most heterogeneous genomes (containing the most candidate foreign genes) include members of the genera Bacteroides, Corynebacterium, Desulfotalea, Neisseria, Xylella, and Thermobaculum. PMID:20679093

Davis, James J; Olsen, Gary J

2010-08-02

48

The factors shaping synonymous codon usage in the genome of Burkholderia mallei.  

PubMed

Burkholderia mallei is regarded as a potential biological weapon by the Centers for Disease Control and Prevention. In this study, the main factors shaping codon usage in the genome of B. mallei ATCC 23344 were firstly reported. The results showed that the primary trend in codon usage variation in the B. mallei is due to translational selection; while compositional mutation bias is relatively the weaker influence and the hydrophobicity of each protein and gene length are only the minor influences. At the same time, 21 codons defined firstly as 'optimal codons' might provide more useful information for the expression of target genes and development of a vaccine to prevent glanders. PMID:17498635

Zhao, Sheng; Zhang, Qin; Chen, Zhihua; Zhao, Yixin; Zhong, Jincheng

2007-04-01

49

A comparative analysis on the synonymous codon usage pattern in viral functional genes and their translational initiation region of ASFV.  

PubMed

The synonymous codon usage pattern of African swine fever virus (ASFV), the similarity degree of the synonymous codon usage between this virus and some organisms and the synonymous codon usage bias for the translation initiation region of viral functional genes in the whole genome of ASFV have been investigated by some simply statistical analyses. Although both GC12% (the GC content at the first and second codon positions) and GC3% (the GC content at the third codon position) of viral functional genes have a large fluctuation, the significant correlations between GC12 and GC3% and between GC3% and the first principal axis of principle component analysis on the relative synonymous codon usage of the viral functional genes imply that mutation pressure of ASFV plays an important role in the synonymous codon usage pattern. Turning to the synonymous codon usage of this virus, the codons with U/A end predominate in the synonymous codon family for the same amino acid and a weak codon usage bias in both leading and lagging strands suggests that strand compositional asymmetry does not take part in the formation of codon usage in ASFV. The interaction between the absolute codon usage bias and GC3% suggests that other selections take part in the formation of codon usage, except for the mutation pressure. It is noted that the similarity degree of codon usage between ASFV and soft tick is higher than that between the virus and the pig, suggesting that the soft tick plays a more important role than the pig in the codon usage pattern of ASFV. The translational initiation region of the viral functional genes generally have a strong tendency to select some synonymous codons with low GC content, suggesting that the synonymous codon usage bias caused by translation selection from the host takes part in modulating the translation initiation efficiency of ASFV functional genes. PMID:23161403

Zhou, Jian-Hua; Gao, Zong-Liang; Sun, Dong-Jie; Ding, Yao-Zhong; Zhang, Jie; Stipkovits, Laszlo; Szathmary, Susan; Pejsak, Zygmunt; Liu, Yong-Sheng

2012-11-16

50

Synonymous codon usage in forty staphylococcal phages identifies the factors controlling codon usage variation and the phages suitable for phage therapy.  

PubMed

The immergence and dissemination of multidrug-resistant strains of Staphylococcus aureus in recent years have expedited the research on the discovery of novel anti-staphylococcal agents promptly. Bacteriophages have long been showing tremendous potentialities in curing the infections caused by various pathogenic bacteria including S. aureus. Thus far, only a few virulent bacteriophages, which do not carry any toxin-encoding gene but are capable of eradicating staphylococcal infections, were reported. Based on the codon usage analysis of sixteen S. aureus phages, previously three phages were suggested to be useful as the anti-staphylococcal agents. To search for additional S. aureus phages suitable for phage therapy, relative synonymous codon usage bias has been investigated in the protein-coding genes of forty new staphylococcal phages. All phages appeared to carry A and T ending codons. Several factors such as mutational pressure, translational selection and gene length seemed to be responsible for the codon usage variation in the phages. Codon usage indeed varied phage to phage. Of the phages, phages G1, Twort, 66 and Sap-2 may be extremely lytic in nature as majority of their genes possess high translational efficiency, indicating that these phages may be employed in curing staphylococcal infections. PMID:23275718

Bishal, Arghya Kamal; Saha, Soumya; Sau, Keya

2012-12-08

51

Variation in the strength of selected codon usage bias among bacteria  

Microsoft Academic Search

Among bacteria, many species have synonymous codon usage patterns that have been influenced by natural selection for those codons that are translated more accurately and\\/or efficiently. However, in other species selection appears to have been ineffective. Here, we introduce a population genetics-based model for quantifying the extent to which selection has been effective. The approach is applied to 80 phylogenetically

Paul M. Sharp; Elizabeth Bailes; Russell J. Grocock; John F. Peden; R. Elizabeth Sockett

2005-01-01

52

Effect of Correlated tRNA Abundances on Translation Errors and Evolution of Codon Usage Bias  

Microsoft Academic Search

Despite the fact that tRNA abundances are thought to play a major role in determining translation error rates, their distribution across the genetic code and the resulting implications have received little attention. In general, studies of codon usage bias (CUB) assume that codons with higher tRNA abundance have lower missense error rates. Using a model of protein translation based on

Premal Shah; Michael A. Gilchrist

2010-01-01

53

Codon usage and G+C content in Bradyrhizobium japonicum genes are not uniform  

Microsoft Academic Search

To date, the sequences of 45 Bradyrhizobium japonicum genes are known. This provides sufficient information to determine their codon usage and G+C content. Surprisingly, B. japonicum nodulation and NifA-regulated genes were found to have a less biased codon usage and a lower G+C content than genes not belonging to these two groups. Thus, the coding regions of nodulation genes and

Tom M. Ramseier; Michael Giittfert

1991-01-01

54

Translational selection is operative for synonymous codon usage in Clostridium perfringens and Clostridium acetobutylicum  

Microsoft Academic Search

Here, the codon usage patterns of two Clostridium species (Clostridium perfringens and Clostridium acetobutylicum) are reported. These prokaryotes are characterized by a strong mutational bias towards A+T, a striking excess of coding sequences and purine-rich leading strands of replication, strong GC-skews and a high frequency of genomic rearrangements. As expected, it was found that the mutational bias dominates codon usage

Hector Musto; Hector Romero; Alejandro Zavala

2003-01-01

55

Statistical analysis of pentose phosphate pathway genes from eubacteria and eukarya reveals translational selection as a major force in shaping codon usage pattern  

PubMed Central

Comparative analysis of metabolic pathways among widely diverse species provides an excellent opportunity to extract information about the functional relation of organisms and pentose phosphate pathway exemplifies one such pathway. A comparative codon usage analysis of the pentose phosphate pathway genes of a diverse group of organisms representing different niches and the related factors affecting codon usage with special reference to the major forces influencing codon usage patterns was carried out. It was observed that organism specific codon usage bias percolates into vital metabolic pathway genes irrespective of their near universality. A clear distinction in the codon usage pattern of gram positive and gram negative bacteria, which is a major classification criterion for bacteria, in terms of pentose phosphate pathway was an important observation of this study. The codon utilization scheme in all the organisms indicates the presence of translation selection as a major force in shaping codon usage. Another key observation was the segregation of the H. sapiens genes as a separate cluster by correspondence analysis, which is primarily attributed to the different codon usage pattern in this genus along with its longer gene lengths. We have also analyzed the amino acid distribution comparison of transketolase protein primary structures among all the organisms and found that there is a certain degree of predictability in the composition profile except in A. fumigatus and H. sapiens, where few exceptions are prominent. In A. fumigatus, a human pathogen responsible for invasive aspergillosis, a significantly different codon usage pattern, which finally translated into its amino acid composition model portraying a unique profile in a key pentose phosphate pathway enzyme transketolase was observed.

Pal, Ayon; Mukhopadhyay, Subhasis; Bothra, Asim Kumar

2013-01-01

56

Mutational and Selective Pressures on Codon and Amino Acid Usage in Buchnera, Endosymbiotic Bacteria of Aphids  

Microsoft Academic Search

We have explored compositional variation at synonymous (codon usage) and nonsynonymous (amino acid usage) positions in three complete genomes of Buchnera, endosymbiotic bacteria of aphids, and also in their orthologs in Escherichia coli, a close free-living relative. We sought to discriminate genes of variable expression levels in order to weigh the relative contributions of mutational bias and selection in the

Claude Rispe; Francois Delmotte; Roeland C. H. J. van Ham; Andres Moya

2003-01-01

57

Functional role of bacteriophage transfer RNAs: codon usage analysis of genomic sequences stored in the GENBANK\\/EMBL\\/DDBJ databases  

Microsoft Academic Search

Complete genomic sequence data are stored in the public GenBank\\/EMBL\\/DDBJ databases so that any investigator can make use of the data. This report describes a comparative analysis of codon usage that is impossible without such a public and open data system. A limited number of bacteriophages harbor their own transfer RNAs. Based on a comparison between T4 phage-encoded tRNA species

T. Kunisawa

2002-01-01

58

Codon usage bias from tRNA's point of view: Redundancy, specialization, and efficient decoding for translation optimization  

Microsoft Academic Search

The selection-mutation-drift theory of codon usage plays a major role in the theory of molecular evolution by explaining the co-evolution of codon usage bias and tRNA content in the framework of translation optimization. Because most studies have focused only on codon usage, we analyzed the tRNA gene pool of 102 bacterial species. We show that as minimal generation times get

Eduardo P. C. Rocha

2004-01-01

59

Translational selection frequently overcomes genetic drift in shaping synonymous codon usage patterns in vertebrates.  

PubMed

Synonymous codon usage patterns are shaped by a balance between mutation, drift, and natural selection. To date, detection of translational selection in vertebrates has proven to be a challenging task, obscured by small long-term effective population sizes in larger animals and the existence of isochores in some species. The consensus is that, in such species, natural selection is either completely ineffective at overcoming mutational pressures and genetic drift or perhaps is effective but so weak that it is not detectable. The aim of this research is to understand the interplay between mutation, selection, and genetic drift in vertebrates. We observe that although variation in mutational bias is undoubtedly the dominant force influencing codon usage, translational selection acts as a weak additional factor influencing synonymous codon usage. These observations indicate that translational selection is a widespread phenomenon in vertebrates and is not limited to a few species. PMID:23883522

Doherty, Aoife; McInerney, James O

2013-07-24

60

Analysis of Codon Usage Patterns in Toxic Dinoflagellate Alexandrium tamarense through Expressed Sequence Tag Data  

PubMed Central

We have analyzed synonymous codon usage in the genome of A. tamarense CCMP 1598 for protein-coding sequences from 10865 expressed sequence tags (ESTs). We reconstructed a total of 4284 unigenes, including 74 ribosomal protein and 40 plastid-related genes, from ESTs using FrameDP, an open reading frame (ORF) prediction program. Correspondence analysis of A. tamarense genes based on codon usage showed that the GC content at the third base of synonymous codons (GC3s) was strongly correlated with the first axis (r = 0.93 with P < .001). On the other hand, the second axis discriminated between presumed highly and low expressed genes, with expression levels being confirmed by the analysis of EST frequencies (r = ?0.89 with P < .001). Our results suggest that mutational bias is the major factor in shaping codon usage in A. tamarense genome, but other factors, namely, translational selection, hydropathy, and aromaticity, also appear to influence the selection of codon usage in this species.

Hsiao, Yi-Yuong; Lin, Chorng-Horng; Liu, Jong-Kang; Wong, Tit-Yee; Kuo, Jimmy

2010-01-01

61

Non-optimal codon usage is a mechanism to achieve circadian clock conditionality  

PubMed Central

Circadian rhythms are oscillations in biological processes that function as a key adaptation to the daily rhythms of most environments. In the model cyanobacterial circadian clock system, the core oscillator proteins are encoded by the gene cluster kaiABC1. Genes with high expression and functional importance like the kai genes are usually encoded by optimal codons, yet the codon usage bias of the kaiBC genes is not optimized for translational efficiency. We discovered a relationship between codon usage and a general property of circadian rhythms called conditionality; namely, that endogenous rhythmicity is robustly expressed under some environmental conditions but not under others2. Despite the generality of circadian conditionality, however, its molecular basis is unknown for any system. Here we show that non-optimal codon usage was selected as a post-transcriptional mechanism to switch between circadian and non-circadian regulation of gene expression as an adaptive response to environmental conditions. When the kaiBC sequence was experimentally optimized to enhance expression of the KaiB and KaiC proteins, intrinsic rhythmicity was enhanced at cool temperatures that are experienced by this organism in its natural habitat. However, fitness at those temperatures was highest in cells whose endogenous rhythms were suppressed at cool temperatures as compared with cells exhibiting high-amplitude rhythmicity. These results indicate natural selection against circadian systems in cyanobacteria that are intrinsically robust at cool temperatures. Modulation of circadian amplitude is therefore critical to its adaptive significance3. Moreover, these results show the direct effects of codon usage on a complex phenotype and organismal fitness. Our work also challenges the long-standing view of directional selection towards optimal codons4–7, and provides a key example of natural selection against optimal codon to achieve adaptive responses to environmental changes.

Xu, Yao; Ma, Peijun; Shah, Premal; Rokas, Antonis; Liu, Yi; Johnson, Carl Hirschie

2013-01-01

62

Single Nucleotide polymorphisms and their relationship to codon usage bias in the Pacific oyster Crassostrea gigas  

Microsoft Academic Search

DNA sequence polymorphism and codon usage bias were investigated in a set of 41 nuclear loci in the Pacific oyster Crassostrea gigas. Our results revealed a very high level of DNA polymorphism in oysters, in the order of magnitude of the highest levels reported in animals to date. A total of 290 single nucleotide polymorphisms (SNPs) were detected, 76 of

C. Sauvage; N. Bierne; S. Lapègue; P. Boudry

2007-01-01

63

Incorporating PCA and fuzzy-ART techniques into achieve organism classification based on codon usage consideration  

Microsoft Academic Search

To recognize the DNA sequence and mine the hidden information to achieve the classification of organisms are viewed as a difficult work to biologists. As we know, the amino acids are the basic elements to construct DNA. Hence, if the codon usage of amino acids can be analyzed well, the useful information about classification of organisms may be obtained. However,

Kun-Lin Hsieh; I-Ching Yang

2008-01-01

64

Is DNA Code Periodicity Only Due to CUF - Codons Usage Frequency?  

Microsoft Academic Search

The triplet code for proteins and functional RNA has been either from the universal pattern of ancient RNA (- HI) [1], with a key role of an uneven codon usage frequency (CUF) in the periodic patterns origination, or a reading frame monitoring device (RFMD -H2) [2- 4]. HI has lately been upheld [1] but in a single sequence sensitive way

Mariusz Zoltowski; Nicolaus Copernicus

2007-01-01

65

Determination of the Relative Importance of Gene Function or Taxonomic Grouping to Codon Usage Bias Using Cluster Analysis and SVMs  

Microsoft Academic Search

The codon usage patterns of 2,552 major histocompatibility complex (MHC) sequences from 33 primate species, and the consequent subsets of sequences obtained by removing species with most abundant sequences was observed. The correlation between function and species with regards to MHC codon usage patterns was analyzed using cluster analysis and support vector machines (SVMs). The results show that gene function

Jianmin Ma; Minh Ngoc Nguyen; Gary B. Fogel; Jagath C. Rajapakse

2006-01-01

66

Comparative study on factors influencing the codon and amino acid usage in Lactobacillus sakei 23K and 13 other lactobacilli  

Microsoft Academic Search

In this study, major factors shaping codon and amino acid usage variation Lactobacillus sakei 23K were investigated. It included 13 other Lactobacillus species for a comparative analysis. The correspondence analysis (COA) showed that in 13 species the major trend of synonymous\\u000a codon usage was highly correlated with gene expression level as assessed by the “Codon Adaptation Index” (CAI) values. In

Kinshuk Chandra Nayak

67

Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights.  

PubMed

The purpose of this study was to investigate the balance between transfer ribonucleic acid (tRNA) supply and demand in retrovirus-infected cells, seeking the best targets for antiretroviral therapy based on the hypothetical tRNA Inhibition Therapy (TRIT). Codon usage and tRNA gene data were retrieved from public databases. Based on logistic principles, a therapeutic score (T-score) was calculated for all sense codons, in each retrovirus-host system. Codons that are critical for viral protein translation, but not as critical for the host, have the highest T-score values. Theoretically, inactivating the cognate tRNA species should imply a severe reduction of the elongation rate during viral mRNA translation. We developed a method to predict tRNA species critical for retroviral protein synthesis. Four of the best TRIT targets in HIV-1 and HIV-2 encode Large Hydrophobic Residues (LHR), which have a central role in protein folding. One of them, codon CUA, is also a TRIT target in both HTLV-1 and HTLV-2. Therefore, a drug designed for inactivating or reducing the cytoplasmatic concentration of tRNA species with anticodon TAG could attenuate significantly both HIV and HTLV protein synthesis rates. Inversely, replacing codons ending in UA by synonymous codons should increase the expression, which is relevant for DNA vaccine design. PMID:24151425

Frias, Diego; Monteiro-Cunha, Joana P; Mota-Miranda, Aline C; Fonseca, Vagner S; de Oliveira, Tulio; Galvao-Castro, Bernardo; Alcantara, Luiz C J

2013-10-10

68

Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights  

PubMed Central

The purpose of this study was to investigate the balance between transfer ribonucleic acid (tRNA) supply and demand in retrovirus-infected cells, seeking the best targets for antiretroviral therapy based on the hypothetical tRNA Inhibition Therapy (TRIT). Codon usage and tRNA gene data were retrieved from public databases. Based on logistic principles, a therapeutic score (T-score) was calculated for all sense codons, in each retrovirus-host system. Codons that are critical for viral protein translation, but not as critical for the host, have the highest T-score values. Theoretically, inactivating the cognate tRNA species should imply a severe reduction of the elongation rate during viral mRNA translation. We developed a method to predict tRNA species critical for retroviral protein synthesis. Four of the best TRIT targets in HIV-1 and HIV-2 encode Large Hydrophobic Residues (LHR), which have a central role in protein folding. One of them, codon CUA, is also a TRIT target in both HTLV-1 and HTLV-2. Therefore, a drug designed for inactivating or reducing the cytoplasmatic concentration of tRNA species with anticodon TAG could attenuate significantly both HIV and HTLV protein synthesis rates. Inversely, replacing codons ending in UA by synonymous codons should increase the expression, which is relevant for DNA vaccine design.

Frias, Diego; Monteiro-Cunha, Joana P.; Mota-Miranda, Aline C.; Fonseca, Vagner S.; de Oliveira, Tulio; Galvao-Castro, Bernardo; Alcantara, Luiz C. J.

2013-01-01

69

Mutation pressure shapes codon usage in the GC-Rich genome of foot-and-mouth disease virus.  

PubMed

Foot-and-mouth disease (FMD) is economically the most important viral-induced livestock disease worldwide. In this study, we report the results of a survey of codon usage bias of FMD virus (FMDV) representing all seven serotypes (A, O, C, Asia 1, SAT 1, SAT 2, and SAT 3). Correspondence analysis, a commonly used multivariate statistical approach, was carried out to analyze synonymous codon usage bias. The analysis showed that the overall extent of codon usage bias in FMDV is low. Furthermore, the good correlation between the frequency of G + C at the synonymous third position of sense codons (GC3S) content at silent sites of each sequence and codon usage bias suggested that mutation pressure rather than natural (translational) selection is the most important determinant of the codon bias observed. In addition, other factors, such as the lengths of open reading frame (ORF) and the hydrophobicity of genes also influence the codon usage variation among the genomes of FMDV in a minor way. The result of phylogenetic analyses based on the relative synonymous codon usage (RSCU) values indicated a few obvious phylogenetic incongruities, which suggest that more FMDV genome diversity may exist in nature than is currently indicated. Our work might give some clues to the features of FMDV genome and some evolutionary information of this virus. PMID:17768673

Zhong, Jincheng; Li, Yanmin; Zhao, Sheng; Liu, Shenggang; Zhang, Zhidong

2007-09-01

70

Selection at the amino acid level can influence synonymous codon usage: implications for the study of codon adaptation in plastid genes.  

PubMed Central

A previously employed method that uses the composition of noncoding DNA as the basis of a test for selection between synonymous codons in plastid genes is reevaluated. The test requires the assumption that in the absence of selective differences between synonymous codons the composition of silent sites in coding sequences will match the composition of noncoding sites. It is demonstrated here that this assumption is not necessarily true and, more generally, that using compositional properties to draw inferences about selection on silent changes in coding sequences is much more problematic than commonly assumed. This is so because selection on nonsynonymous changes can influence the composition of synonymous sites (i.e., codon usage) in a complex manner, meaning that the composition biases of different silent sites, including neutral noncoding DNA, are not comparable. These findings also draw into question the commonly utilized method of investigating how selection to increase translation accuracy influences codon usage. The work then focuses on implications for studies that assess codon adaptation, which is selection on codon usage to enhance translation rate, in plastid genes. A new test that does not require the use of noncoding DNA is proposed and applied. The results of this test suggest that far fewer plastid genes display codon adaptation than previously thought.

Morton, B R

2001-01-01

71

Evolutionary Basis of Codon Usage and Nucleotide Composition Bias in Vertebrate DNA Viruses  

Microsoft Academic Search

Understanding the extent and causes of biases in codon usage and nucleotide composition is essential to the study of viral\\u000a evolution, particularly the interplay between viruses and host cells or immune responses. To understand the common features\\u000a and differences among viruses we analyzed the genomic characteristics of a representative collection of all sequenced vertebrate-infecting\\u000a DNA viruses. This revealed that patterns

Laura A. Shackelton; Colin R. Parrish; Edward C. Holmes

2006-01-01

72

Translational selection shapes codon usage in the GC-rich genome of Chlamydomonas reinhardtii  

Microsoft Academic Search

In unicellular species codon usage is determined by mutational biases and natural selection. Among prokaryotes, the influence of these factors is different if the genome is skewed towards AT or GC, since in AT-rich organisms translational selection is absent. On the other hand, in AT-rich unicellular eukaryotes the two factors are present. In order to understand if GC-rich genomes display

Hugo Naya; Héctor Romero; Nicola Carels; Alejandro Zavala; Héctor Musto

2001-01-01

73

Mutational Bias and Translational Selection Shaping the Codon Usage Pattern of Tissue-Specific Genes in Rice  

PubMed Central

The regulatory mechanisms of determining which genes specifically expressed in which tissues are still not fully elucidated, especially in plants. Using internal correspondence analysis, I first establish that tissue-specific genes exhibit significantly different synonymous codon usage in rice, although this effect is weak. The variability of synonymous codon usage between tissues accounts for 5.62% of the total codon usage variability, which has mainly arisen from the neutral evolutionary forces, such as GC content variation among tissues. Moreover, tissue-specific genes are under differential selective constraints, inferring that natural selection also contributes to the codon usage divergence between tissues. These findings may add further evidence in understanding the differentiation and regulation of tissue-specific gene products in plants.

Liu, Qingpo

2012-01-01

74

Enhanced expression in tobacco of the gene encoding green fluorescent protein by modification of its codon usage  

Microsoft Academic Search

The gene encoding green fluorescent protein (GFP) from Aequorea victoria was resynthesized to adapt its codon usage for expression in plants by increasing the frequency of codons with a C or a G in the third position from 32 to 60%. The strategy for constructing the synthetic gfp gene was based on the overlap extension PCR method using 12 long

Odette Mendes; Emil J. H. Wolbert; A. Douwe de Boer

1997-01-01

75

Increased Immune Response Elicited by DNA Vaccination with a Synthetic gp120 Sequence with Optimized Codon Usage  

Microsoft Academic Search

DNA vaccination elicits humoral and cellular immune responses and has been shown to confer protection against several viral, bacterial, and parasitic pathogens. Here we report that optimized codon usage of an injected DNA sequence considerably increases both humoral and cellular immune responses. We recently generated a synthetic human immunodeficiency virus type 1 gp120 sequence in which most wild-type codons were

STEFANIE ANDRE; BRIAN SEED; JOSEF EBERLE; WINFRIED SCHRAUT; ANDREAS BULTMANN; JURGEN HAAS

1998-01-01

76

Evolutionary Constraints on Codon and Amino Acid Usage in Two Strains of Human Pathogenic Actinobacteria Tropheryma whipplei  

Microsoft Academic Search

The factors governing codon and amino acid usages in the predicted protein-coding sequences of Tropheryma whipplei TW08\\/27 and Twist genomes have been analyzed. Multivariate analysis identifies the replicational-transcriptional selection\\u000a coupled with DNA strand-specific asymmetric mutational bias as a major driving force behind the significant interstrand variations\\u000a in synonymous codon usage patterns in T. whipplei genes, while a residual intrastrand synonymous

Sabyasachi Das; Sandip Paul; Chitra Dutta

2006-01-01

77

Environmental shaping of codon usage and functional adaptation across microbial communities.  

PubMed

Microbial communities represent the largest portion of the Earth's biomass. Metagenomics projects use high-throughput sequencing to survey these communities and shed light on genetic capabilities that enable microbes to inhabit every corner of the biosphere. Metagenome studies are generally based on (i) classifying and ranking functions of identified genes; and (ii) estimating the phyletic distribution of constituent microbial species. To understand microbial communities at the systems level, it is necessary to extend these studies beyond the species' boundaries and capture higher levels of metabolic complexity. We evaluated 11 metagenome samples and demonstrated that microbes inhabiting the same ecological niche share common preferences for synonymous codons, regardless of their phylogeny. By exploring concepts of translational optimization through codon usage adaptation, we demonstrated that community-wide bias in codon usage can be used as a prediction tool for lifestyle-specific genes across the entire microbial community, effectively considering microbial communities as meta-genomes. These findings set up a 'functional metagenomics' platform for the identification of genes relevant for adaptations of entire microbial communities to environments. Our results provide valuable arguments in defining the concept of microbial species through the context of their interactions within the community. PMID:23921637

Roller, Masa; Lucic, Vedran; Nagy, István; Perica, Tina; Vlahovicek, Kristian

2013-08-05

78

Environmental shaping of codon usage and functional adaptation across microbial communities  

PubMed Central

Microbial communities represent the largest portion of the Earth’s biomass. Metagenomics projects use high-throughput sequencing to survey these communities and shed light on genetic capabilities that enable microbes to inhabit every corner of the biosphere. Metagenome studies are generally based on (i) classifying and ranking functions of identified genes; and (ii) estimating the phyletic distribution of constituent microbial species. To understand microbial communities at the systems level, it is necessary to extend these studies beyond the species’ boundaries and capture higher levels of metabolic complexity. We evaluated 11 metagenome samples and demonstrated that microbes inhabiting the same ecological niche share common preferences for synonymous codons, regardless of their phylogeny. By exploring concepts of translational optimization through codon usage adaptation, we demonstrated that community-wide bias in codon usage can be used as a prediction tool for lifestyle-specific genes across the entire microbial community, effectively considering microbial communities as meta-genomes. These findings set up a ‘functional metagenomics’ platform for the identification of genes relevant for adaptations of entire microbial communities to environments. Our results provide valuable arguments in defining the concept of microbial species through the context of their interactions within the community.

Roller, Masa; Lucic, Vedran; Nagy, Istvan; Perica, Tina; Vlahovicek, Kristian

2013-01-01

79

Differential Trends in the Codon Usage Patterns in HIV-1 Genes  

PubMed Central

Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host–pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation, selection, and genetic drift is known to maintain codon bias in both organisms. Studies revealing determinants of the bias and its dynamics are central to the understanding of host-pathogen evolution. We considered the Human Immunodeficiency Virus (HIV) type 1 and its human host to search for evolutionary signatures in the viral genome. Positive selection is known to dominate intra-host evolution of HIV-1, whereas high genetic variability underlies the belief that neutral processes drive inter-host differences. In this study, we analyze the codon usage patterns of HIV-1 genomes across all subtypes and clades sequenced over a period of 23 years. We show presence of unique temporal correlations in the codon bias of three HIV-1 genes illustrating differential adaptation of the HIV-1 genes towards the host preferred codons. Our results point towards gene-specific translational selection to be an important force driving the evolution of HIV-1 at the population level.

Pandit, Aridaman; Sinha, Somdatta

2011-01-01

80

On Relevance of Codon Usage to Expression of Synthetic and Natural Genes in Escherichia coli  

PubMed Central

A recent investigation concluded that codon bias did not affect expression of green fluorescent protein (GFP) variants in Escherichia coli, while stability of an mRNA secondary structure near the 5? end played a dominant role. We demonstrate that combining the two variables using regression trees or support vector regression yields a biologically plausible model with better support in the GFP data set and in other experimental data: codon usage is relevant for protein levels if the 5? mRNA structures are not strong. Natural E. coli genes had weaker 5? mRNA structures than the examined set of GFP variants and did not exhibit a correlation between the folding free energy of 5? mRNA structures and protein expression.

Supek, Fran; Smuc, Tomislav

2010-01-01

81

The effect of altered codon usage on luciferase activity in tobacco, maize and wheat  

Microsoft Academic Search

A comparison of the wild-type firefly luciferase reporter gene to a codon-modified gene, available from Promega, demonstrates\\u000a that in tobacco cell cultures, an increase in G+C content of 1.8%, as a consequence of 36 A\\/T?G\\/C synonymous codon alterations\\u000a and removal of the lysosomal targeting sequence, has no significant effect on expression. In maize Black Mexican Sweet cells\\u000a and wheat scutellum,

D. M. Lonsdale; L. J. Moisan; A. J. Harvey

1998-01-01

82

Phylogenetic Artifacts Can be Caused by Leucine, Serine, and Arginine Codon Usage Heterogeneity: Dinoflagellate Plastid Origins as a Case Study  

Microsoft Academic Search

Phylogenetic analyses of first and second codon positions (DNA 1+2 analysis) and amino acid sequences (protein analysis) are often thought to provide similar estimates of deep-level phylogeny. However, here we report a novel artifact influencing DNA level phylogenetic inference of protein-coding genes introduced by codon usage heterogeneity that causes significant incongruities between DNA 1+2 and protein analyses. DNA 1+2 analyses

YUJI INAGAKI; ALASTAIR G. B. SIMPSON; JOEL B. DACKS; ANDREW J. ROGER

2004-01-01

83

Chloroplast genes transferred to the nuclear plant genome have adjusted to nuclear base composition and codon usage.  

PubMed Central

During plant evolution, some plastid genes have been moved to the nuclear genome. These transferred genes are now correctly expressed in the nucleus, their products being transported into the chloroplast. We compared the base compositions, the distributions of some dinucleotides and codon usages of transferred, nuclear and chloroplast genes in two dicots and two monocots plant species. Our results indicate that transferred genes have adjusted to nuclear base composition and codon usage, being now more similar to the nuclear genes than to the chloroplast ones in every species analyzed.

Oliver, J L; Marin, A; Martinez-Zapater, J M

1990-01-01

84

Synonymous codon usage bias is correlative to intron number and shows disequilibrium among exons in plants  

PubMed Central

Background Evidence has been assembled to suggest synonymous codon usage bias (SCUB) has close relationship with intron. However, the relationship (if any) between SCUB and intron number as well as exon position is at present rather unclear. Results To explore this relationship, the sequences of a set of genes containing between zero and nine introns was extracted from the published genome sequences of three algal species, one moss, one fern and six angiosperms (three monocotyledonous species and three dicotyledonous species). In the algal genomes, the frequency of synonymous codons of the form NNG/NNC (codons with G and C at the third position) was positively related to intron number, but that of NNA/NNT was inversely correlated; the opposite was the case in the land plant genomes. The frequency of NNC/NNG was higher and that of NNA/NNT lower in two terminal exons than in the interstitial exons in the land plant genes, but the rule showed to be opposite in the algal genes. SCUB patterns in the interstitial and two terminal exons mirror the different evolutionary relationships between these plant species, while the first exon shows the highest level of conservation is therefore concluded to be the one which experiences the heaviest selection pressure. The phenomenon of SCUB may also be related to DNA methylation induced conversion of CG to AT. Conclusions These data provide some evidence of linkage between SCUB, the evolution of introns and DNA methylation, which brings about a new perspective for understanding how genomic variation is created during plant evolution.

2013-01-01

85

Production of ?-cyclodextrin glycosyltransferase in Bacillus megaterium MS941 by systematic codon usage optimization.  

PubMed

?-Cyclodextrin glycosyltransferase is a key enzyme in the cyclodextrin industry. The Gram-positive bacterium Bacillus megaterium was chosen for production of recombinant ?-CGTase for safety concerns. Successful production of heterologous ?-CGTase was achieved by adapting the original ?-cgt gene to the codon usage of B. megaterium by systematic codon optimization. This balanced the tRNA pool and reduced ribosomal traffic jams. Protein expression and secretion was ensured by using the strong inducible promoter P(xyl) and the signal peptide SP(LipA). The impact of culture medium composition and induction strategies on ?-CGTase production was systematically analyzed. Production and secretion at 32 °C for 24 h using modified culture medium was optimal for ?-CGTase yield. Batch- and simple fed-batch fermentation was applied to achieve a high yield of 48.9 U·mL(-1), which was the highest activity reported for a Bacillus species, making this production system a reasonable alternative to Escherichia coli. PMID:23013320

Zhou, Jingwen; Liu, Hua; Du, Guocheng; Li, Jianghua; Chen, Jian

2012-10-08

86

Studies on synonymous codon and amino acid usages in Aeromonas hydrophila phage Aeh1: architecture of protein-coding genes and therapeutic implications  

Microsoft Academic Search

Background and Purpose: Codon and amino acid usage biases determined in numerous organisms have deciphered the architectures of their protein-coding genes to some extent. To understand the architecture of protein-coding genes of Aeromonas phages, codon and amino acid usage biases have been investigated in the protein-coding genes of the Aeromonas hydrophila phage Aeh1. Methods: In order to study synonymous codon

Keya Sau

2007-01-01

87

Selection on Codon Usage for Error Minimization at the Protein Level  

Microsoft Academic Search

Given the structure of the genetic code, synonymous codons differ in their capacity to minimize the effects of errors due to mutation or mistranslation. I suggest that this may lead, in protein-coding genes, to a preference for codons that minimize the impact of errors at the protein level. I develop a theoretical measure of error minimization for each codon, based

Marco Archetti

2004-01-01

88

Co-Evolution of Mitochondrial tRNA Import and Codon Usage Determines Translational Efficiency in the Green Alga Chlamydomonas  

PubMed Central

Mitochondria from diverse phyla, including protozoa, fungi, higher plants, and humans, import tRNAs from the cytosol in order to ensure proper mitochondrial translation. Despite the broad occurrence of this process, our understanding of tRNA import mechanisms is fragmentary, and crucial questions about their regulation remain unanswered. In the unicellular green alga Chlamydomonas, a precise correlation was found between the mitochondrial codon usage and the nature and amount of imported tRNAs. This led to the hypothesis that tRNA import might be a dynamic process able to adapt to the mitochondrial genome content. By manipulating the Chlamydomonas mitochondrial genome, we introduced point mutations in order to modify its codon usage. We find that the codon usage modification results in reduced levels of mitochondrial translation as well as in subsequent decreased levels and activities of respiratory complexes. These effects are linked to the consequential limitations of the pool of tRNAs in mitochondria. This indicates that tRNA mitochondrial import cannot be rapidly regulated in response to a novel genetic context and thus does not appear to be a dynamic process. It rather suggests that the steady-state levels of imported tRNAs in mitochondria result from a co-evolutive adaptation between the tRNA import mechanism and the requirements of the mitochondrial translation machinery.

Salinas, Thalia; Duby, Franceline; Larosa, Veronique; Coosemans, Nadine; Bonnefoy, Nathalie; Motte, Patrick; Marechal-Drouard, Laurence; Remacle, Claire

2012-01-01

89

Codon usage tabulated from international DNA sequence databases: status for the year 2000  

Microsoft Academic Search

The frequencies of each of the 257 468 complete protein coding sequences (CDSs) have been compiled from the taxonomical divisions of the GenBank DNA sequence database. The sum of the codons used by 8792 organisms has also been calculated. The data files can be obtained from the anonymous ftp sites of DDBJ, Kazusa and EBI. A list of the codon

Yasukazu Nakamura; Takashi Gojobori; Toshimichi Ikemura

2000-01-01

90

Codon usage bias and tRNA over-expression in Buchnera aphidicola after aromatic amino acid nutritional stress on its host Acyrthosiphon pisum  

Microsoft Academic Search

Codon usage bias and relative abundances of tRNA isoacceptors were analysed in the obligate intracellular symbiotic bacterium, Buchnera aphidi- cola from the aphid Acyrthosiphon pisum, using a dedicated 35mer oligonucleotide microarray. Buchnera is archetypal of organisms living with minimal metabolic requirements and presents a reduced genome with high-evolutionary rate. Codon usage in Buchnera has been overcome by the high mutational

Hubert Charles; Federica Calevro; J. Vinuelas; J.-M. Fayard; Y. Rahbe

2006-01-01

91

Increased tRNA modification and gene-specific codon usage regulate cell cycle progression during the DNA damage response  

PubMed Central

S-phase and DNA damage promote increased ribonucleotide reductase (RNR) activity. Translation of RNR1 has been linked to the wobble uridine modifying enzyme tRNA methyltransferase 9 (Trm9). We predicted that changes in tRNA modification would translationally regulate RNR1 after DNA damage to promote cell cycle progression. In support, we demonstrate that the Trm9-dependent tRNA modification 5-methoxycarbonylmethyluridine (mcm?U) is increased in hydroxyurea (HU)-induced S-phase cells, relative to G? and G?, and that mcm?U is one of 16 tRNA modifications whose levels oscillate during the cell cycle. Codon-reporter data matches the mcm?U increase to Trm9 and the efficient translation of AGA codons and RNR1. Further, we show that in trm9? cells reduced Rnr1 protein levels cause delayed transition into S-phase after damage. Codon re-engineering of RNR1 increased the number of trm9? cells that have transitioned into S-phase 1 h after DNA damage and that have increased Rnr1 protein levels, similar to that of wild-type cells expressing native RNR1. Our data supports a model in which codon usage and tRNA modification are regulatory components of the DNA damage response, with both playing vital roles in cell cycle progression.

Patil, Ashish; Dyavaiah, Madhu; Joseph, Fraulin; Rooney, John P.; Chan, Clement T.Y.; Dedon, Peter C.; Begley, Thomas J.

2012-01-01

92

Influence of certain forces on evolution of synonymous codon usage bias in certain species of three basal orders of aquatic insects.  

PubMed

Forces that influence the evolution of synonymous codon usage bias are analyzed in six species of three basal orders of aquatic insects. The rationale behind choosing six species of aquatic insects (three from Ephemeroptera, one from Plecoptera, and two from Odonata) for the present analysis is based on phylogenetic position at the basal clades of the Order Insecta facilitating the understanding of the evolution of codon bias and of factors shaping codon usage patterns in primitive clades of insect lineages and their subtle differences in some of their ecological and environmental requirements in terms of habitat-microhabitat requirements, altitudinal preferences, temperature tolerance ranges, and consequent responses to climate change impacts. The present analysis focuses on open reading frames of the 13 protein-coding genes in the mitochondrial genome of six carefully chosen insect species to get a comprehensive picture of the evolutionary intricacies of codon bias. In all the six species, A and T contents are observed to be significantly higher than G and C, and are used roughly equally. Since transcription hypothesis on codon usage demands A richness and T poorness, it is quite likely that mutation pressure may be the key factor associated with synonymous codon usage (SCU) variations in these species because the mutation hypothesis predicts AT richness and GC poorness in the mitochondrial DNA. Thus, AT-biased mutation pressure seems to be an important factor in framing the SCU variation in all the selected species of aquatic insects, which in turn explains the predominance of A and T ending codons in these species. This study does not find any association between microhabitats and codon usage variations in the mitochondria of selected aquatic insects. However, this study has identified major forces, such as compositional constraints and mutation pressure, which shape patterns of codon usage in mitochondrial genes in the primitive clades of insect lineages. PMID:22943112

Selva Kumar, C; Nair, Rahul R; Sivaramakrishnan, K G; Ganesh, D; Janarthanan, S; Arunachalam, M; Sivaruban, T

2012-09-03

93

Codon usage bias and tRNA over-expression in Buchnera aphidicola after aromatic amino acid nutritional stress on its host Acyrthosiphon pisum.  

PubMed

Codon usage bias and relative abundances of tRNA isoacceptors were analysed in the obligate intracellular symbiotic bacterium, Buchnera aphidicola from the aphid Acyrthosiphon pisum, using a dedicated 35mer oligonucleotide microarray. Buchnera is archetypal of organisms living with minimal metabolic requirements and presents a reduced genome with high-evolutionary rate. Codonusage in Buchnera has been overcome by the high mutational bias towards AT bases. However, several lines of evidence for codon usage selection are given here. A significant correlation was found between tRNA relative abundances and codon composition of Buchnera genes. A significant codon usage bias was found for the choice of rare codons in Buchnera: C-ending codons are preferred in highly expressed genes, whereas G-ending codons are avoided. This bias is not explained by GC skew in the bacteria and might correspond to a selection for perfect matching between codon-anticodon pairs for some essential amino acids in Buchnera proteins. Nutritional stress applied to the aphid host induced a significant overexpression of most of the tRNA isoacceptors in bacteria. Although, molecular regulation of the tRNA operons in Buchnera was not investigated, a correlation between relative expression levels and organization in transcription unit was found in the genome of Buchnera. PMID:16963497

Charles, Hubert; Calevro, Federica; Vinuelas, José; Fayard, Jean-Michel; Rahbe, Yvan

2006-09-08

94

The 3-Base Periodicity and Codon Usage of Coding Sequences Are Correlated with Gene Expression at the Level of Transcription Elongation  

PubMed Central

Background Gene transcription is regulated by DNA transcriptional regulatory elements, promoters and enhancers that are located outside the coding regions. Here, we examine the characteristic 3-base periodicity of the coding sequences and analyse its correlation with the genome-wide transcriptional profile of yeast. Principal Findings The analysis of coding sequences by a new class of indices proposed here identified two different sources of 3-base periodicity: the codon frequency and the codon sequence. In exponentially growing yeast cells, the codon-frequency component of periodicity accounts for 71.9% of the variability of the cellular mRNA by a strong association with the density of elongating mRNA polymerase II complexes. The mRNA abundance explains most of the correlation between the codon-frequency component of periodicity and protein levels. Furthermore, pyrimidine-ending codons of the four-fold degenerate small amino acids alanine, glycine and valine are associated with genes with double the transcription rate of those associated with purine-ending codons. Conclusions We demonstrate that the 3-base periodicity of coding sequences is higher than expected by the codon usage frequency (CUF) and that its components, associated with codon bias and amino acid composition, are correlated with gene expression, principally at the level of transcription elongation. This indicates a role of codon sequences in maximising the transcription efficiency in exponentially growing yeast cells. Moreover, the results contrast with the common Darwinian explanation that attributes the codon bias to translational selection by an adjustment of synonymous codon frequencies to the most abundant isoaccepting tRNA. Here, we show that selection on codon bias likely acts at both the transcriptional and translational level and that codon usage and the relative abundance of tRNA could drive each other in order to synergistically optimize the efficiency of gene expression.

Trotta, Edoardo

2011-01-01

95

Comparison of two codon optimization strategies to enhance recombinant protein production in Escherichia coli  

PubMed Central

Background Variations in codon usage between species are one of the major causes affecting recombinant protein expression levels, with a significant impact on the economy of industrial enzyme production processes. The use of codon-optimized genes may overcome this problem. However, designing a gene for optimal expression requires choosing from a vast number of possible DNA sequences and different codon optimization methods have been used in the past decade. Here, a comparative study of the two most common methods is presented using calf prochymosin as a model. Results Seven sequences encoding calf prochymosin have been designed, two using the "one amino acid-one codon" method and five using a "codon randomization" strategy. When expressed in Escherichia coli, the variants optimized by the codon randomization approach produced significantly more proteins than the native sequence including one gene that produced an increase of 70% in the amount of prochymosin accumulated. On the other hand, no significant improvement in protein expression was observed for the variants designed with the one amino acid-one codon method. The use of codon-optimized sequences did not affect the quality of the recovered inclusion bodies. Conclusions The results obtained in this study indicate that the codon randomization method is a superior strategy for codon optimization. A significant improvement in protein expression was obtained for the largely established process of chymosin production, showing the power of this strategy to reduce production costs of industrial enzymes in microbial hosts.

2011-01-01

96

Transfer RNA gene arrangement and codon usage in vertebrate mitochondrial genomes: a new insight into gene order conservation  

PubMed Central

Background Mitochondrial (mt) gene arrangement has been highly conserved among vertebrates from jawless fishes to mammals for more than 500 million years. It remains unclear, however, whether such long-term persistence is a consequence of some constraints on the gene order. Results Based on the analysis of codon usage and tRNA gene positions, we suggest that tRNA gene order of the typical vertebrate mt-genomes may be important for their translational efficiency. The vertebrate mt-genome encodes 2 rRNA, 22 tRNA, and 13 transmembrane proteins consisting mainly of hydrophobic domains. We found that the tRNA genes specifying the hydrophobic residues were positioned close to the control region (CR), where the transcription efficiency is estimated to be relatively high. Using 47 vertebrate mt-genome sequences representing jawless fishes to mammals, we further found a correlation between codon usage and tRNA gene positions, implying that highly-used tRNA genes are located close to the CR. In addition, an analysis considering the asymmetric nature of mtDNA replication suggested that the tRNA loci that remain in single-strand for a longer time tend to have more guanine and thymine not suffering deamination mutations in their anticodon sites. Conclusions Our analyses imply the existence of translational constraint acting on the vertebrate mt-gene arrangement. Such translational constraint, together with the deamination-related constraint, may have contributed to long-term maintenance of gene order.

2010-01-01

97

Codon usage variability determines the correlation between proteome and transcriptome fold changes  

PubMed Central

Background The availability of high throughput experimental methods has made possible to observe the relationships between proteome and transcirptome. The protein abundances show a positive but weak correlation with the concentrations of their cognate mRNAs. This weak correlation implies that there are other crucial effects involved in the regulation of protein translation, different from the sole availability of mRNA. It is well known that ribosome and tRNA concentrations are sources of variation in protein levels. Thus, by using integrated analysis of omics data, genomic information, transcriptome and proteome, we aim to unravel important variables affecting translation. Results We identified how much of the variability in the correlation between protein and mRNA concentrations can be attributed to the gene codon frequencies. We propose the hypothesis that the influence of codon frequency is due to the competition of cognate and near-cognate tRNA binding; which in turn is a function of the tRNA concentrations. Transcriptome and proteome data were combined in two analytical steps; first, we used Self-Organizing Maps (SOM) to identify similarities among genes, based on their codon frequencies, grouping them into different clusters; and second, we calculated the variance in the protein mRNA correlation in the sampled genes from each cluster. This procedure is justified within a mathematical framework. Conclusions With the proposed method we observed that in all the six studied cases most of the variability in the relation protein-transcript could be explained by the variation in codon composition.

2011-01-01

98

Secretory expression and purification of a soluble NADH cytochrome b5 reductase enzyme from Mucor racemosus in Pichia pastoris based on codon usage adaptation  

Microsoft Academic Search

The genome of Mucor racemosus was analyzed to determine the relative levels of codon usage. The codon bias differred from that of Escherichia coli. The active, soluble isoform of NADH cytochrome b5 reductase containing 228 amino acids was successfully overexpressed and\\u000a secreted using alpha factor in Pichia pastoris under the control of the alcohol oxidase promoter and finally purified. The

S. A. Mirzaei; M. Tabatabaei Yazdi; Z. Sepehrizadeh

2010-01-01

99

Newly sequenced eRF1s from ciliates: the diversity of stop codon usage and the molecular surfaces that are important for stop codon interactions.  

PubMed

The genetic code of nuclear genes in some ciliates was found to differ from that of other organisms in the assignment of UGA, UAG, and UAA codons, which are normally assigned as stop codons. In some ciliate species, the universal stop codons UAA and UAG instead encode glutamine. In some other ciliates, the universal stop codon UGA appears to be translated as cysteine or tryptophan. Eukaryotic release factor 1 (eRF1) is a key protein in stop codon recognition, thus, the protein is believed to play an important role in the stop codon reassignment in ciliates. We have cloned, sequenced, and analyzed the cDNA of eRF1 from four ciliate species of three different classes: Karyorelictea (Loxodes striatus), Heterotrichea (Blepharisma musculus), and Litostomatea (Didinium nasutum, Dileptus margaritifer). Phylogenetic analysis of these eRF1s supports the hypothesis that the genetic code in ciliates has deviated independently several times from the universal genetic code, and that different ciliate eRF1s may have undergone different processes to change the codon specificity. Using computational methods, we have also suggested areas on the surface of eRF1s that are important for stop codon recognition in ciliate eRF1s. PMID:15716103

Kim, Oanh Thi Phuong; Yura, Kei; Go, Nobuhiro; Harumoto, Terue

2005-01-04

100

Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region  

Microsoft Academic Search

We replaced degenerate codons for nine amino acids within the capsid region of the Sabin type 2 oral poliovirus vaccine strain with corresponding nonpreferred synonymous codons. Codon replacements were introduced into four contiguous intervals spanning 97% of the capsid region. In the capsid region of the most highly modified virus construct, the effective number of codons used (NC) fell from

Cara Carthel Burns; Jing Shaw; Ray Campagnoli; Jaume Jorba; Annelet Vincent; Jacqueline Quay; Olen Kew

2006-01-01

101

Codon usage in histone gene families of higher eukaryotes reflects functional rather than phylogenetic relationships  

Microsoft Academic Search

Summary The nucleic acid sequences coding for 23 H3 histone genes from a variety of species have been analyzed using a computer assisted alignment and analysis program. Although these histones are highly conserved within and between highly divergent species, they represent various classes of histones whose patterns of expression are distinctively regulated. Surprisingly, in dendrograms derived from these comparisons, H3

Dan Wells; William Bains; Larry Kedes

1986-01-01

102

The effects of the synonymous codon usage and tRNA abundance on protein folding of the 3C protease of foot-and-mouth disease virus.  

PubMed

The 3C protease of foot-and-mouth disease virus (FMDV) has a conserved amino acid sequence and is responsible for most cleavage in the viral polyprotein. The effects of the synonymous codon usage of FMDV 3C gene and tRNA abundance of the hosts on shaping different folding units (?-helix, ?-strand and the coil) in the 3C protease were analyzed based on the structural information of the FMDV 3C protease from Protein Data Bank (PDB: 2BHG) and 210 genes of 3C for all serotypes of FMDV. The strong correlation between some codons usage and the specific folding unit in the FMDV 3C protease is found. As for the effect of translation speed caused by tRNA abundance on the formation of folding units, the codon positions with lowly abundant tRNA scatter in the 3C gene and there is the obvious fluctuation of tRNA abundance locating in the transition boundaries from the ?-strand to the ?-helix and the coil, respectively. However, codon positions with lowly abundant tRNA clustering into these boundaries are not found, suggesting that the adjustment of translation speed is likely also achieved by the single codon position with low tRNA abundance rather than a cluster. The observations can provide the information for insight into the role of the synonymous codon usage in the formation of 3C protease of FMDV and effect of the tRNA abundance of the hosts on this formation of protease. PMID:23499709

Zhou, Jian-hua; You, Ya-nan; Chen, Hao-tai; Zhang, Jie; Ma, Li-na; Ding, Yao-zhong; Pejsak, Zygmunt; Liu, Yong-sheng

2013-03-14

103

Significance of codon usage and irregularities of rare codon distribution in genes for expression of BspLU11III methyltransferases.  

PubMed

Genes of adenine-specific DNA-methyltransferase M.BspLU11IIIa and cytosine-specific DNA-methyltransferase M.BspLU11IIIb of the type IIG BspLU11III restriction-modification system from the thermophilic strain Bacillus sp. LU11 were expressed in E. coli. They contain a large number of codons that are rare in E. coli and are characterized by equal values of codon adaptation index (CAI) and expression level measure (E(g)). Rare codons are either diffused (M.BspLU11IIIa) or located in clusters (M.BspLU11IIIb). The expression level of the cytosine-specific DNA-methyltransferase was increased by a factor of 7.3 and that of adenine-specific DNA only by a factor of 1.25 after introduction of the plasmid pRARE supplying tRNA genes for six rare codons in E. coli. It can be assumed that the plasmid supplying minor tRNAs can strongly increase the expression level of only genes with cluster distribution of rare codons. Using heparin-Sepharose and phosphocellulose chromatography and gel filtration on Sephadex G-75 both DNA-methyltransferases were isolated as electrophoretically homogeneous proteins (according to the results of SDS-PAGE). PMID:15193127

Kirienko, N V; Lepikhov, K A; Zheleznaya, L A; Matvienko, N I

2004-05-01

104

Secretory expression and purification of a soluble NADH cytochrome b5 reductase enzyme from Mucor racemosus in Pichia pastoris based on codon usage adaptation.  

PubMed

The genome of Mucor racemosus was analyzed to determine the relative levels of codon usage. The codon bias differed from that of Escherichia coli. The active, soluble isoform of NADH cytochrome b5 reductase containing 228 amino acids was successfully overexpressed and secreted using alpha factor in Pichia pastoris under the control of the alcohol oxidase promoter and finally purified. The culture medium and incubation time were optimized, and the maximum expression level observed was about 23 U/ml using X-33 recombinant yeast grown for 120 h with 0.5% (v/v) methanol in complex media. PMID:20623315

Mirzaei, S A; Yazdi, M Tabatabaei; Sepehrizadeh, Z

2010-07-11

105

Structural features of multiple nifH-like sequences and very biased codon usage in nitrogenase genes of Clostridium pasteurianum.  

PubMed

The structural gene (nifH1) encoding the nitrogenase iron protein of Clostridium pasteurianum has been cloned and sequenced. It is located on a 4-kilobase EcoRI fragment (cloned into pBR325) that also contains a portion of nifD and another nifH-like sequence (nifH2). C. pasteurianum nifH1 encodes a polypeptide (273 amino acids) identical to that of the isolated iron protein, indicating that the smaller size of the C. pasteurianum iron protein does not result from posttranslational processing. The 5' flanking region of nifH1 or nifH2 does not contain the nif promoter sequences found in several gram-negative bacteria. Instead, a sequence resembling the Escherichia coli consensus promoter (TTGACA-N17-TATAAT) is present before C. pasteurianum nifH2, and a TATAAT sequence is present before C pasteurianum nifH1. Codon usage in nifH1, nifH2, and nifD (partial) is very biased. A preference for A or U in the third position of the codons is seen. nifH2 could encode a protein of 272 amino acid residues, which differs from the iron protein (nifH1 product) in 23 amino acid residues (8%). Another nifH-like sequence (nifH3) is located on a nonadjacent EcoRI fragment and has been partially sequenced. C. pasteurianum nifH2 and nifH3 may encode proteins having several amino acids that are conserved in other proteins but not in C. pasteurianum iron protein, suggesting a possible role for the multiple nifH-like sequences of C. pasteurianum in the evolution of nifH. Among the nine sequenced iron proteins, only the C. pasteurianum protein lacks a conserved lysine residue which is near the extended C terminus of the other iron proteins. The absence of this positive charge in the C. pasteurianum iron protein might affect the cross-reactivity of the protein in heterologous systems. PMID:3457003

Chen, K C; Chen, J S; Johnson, J L

1986-04-01

106

Multiple Effects of Codon Usage Optimization on Expression and Immunogenicity of DNA Candidate Vaccines Encoding the Human Immunodeficiency Virus Type 1 Gag Protein  

Microsoft Academic Search

We have analyzed the influence of codon usage modifications on the expression levels and immunogenicity of DNA vaccines, encoding the human immunodeficiency virus type 1 (HIV-1) group-specific antigen (Gag). In the presence of Rev, an expression vector containing the wild-type (wt) gag gene flanked by essential cis-acting sites such as the 5-untranslated region and 3-Rev response element supported substantial Gag

LUDWIG DEML; ALEXANDRA BOJAK; STEPHANIE STECK; MARCUS GRAF; JENS WILD; REINHOLD SCHIRMBECK; HANS WOLF; RALF WAGNER

2001-01-01

107

Molecular evolution of bacteriophages: Discrete patterns of codon usage in T4 genes are related to the time of gene expression  

Microsoft Academic Search

Summary Patterns of codon usage in certain coliphages are adapted to expression inEscherichia coli. Bacteriophage T4 may be an exception to test the rule, as it produces eight tRNAs with specificities that are otherwise rare inE. coli. A database of all known T4 DNA sequences has been compiled, comprising 174 genes and a total of 115 kb (approximately 70% of

Elizabeth Cowe; Paul M. Sharp

1991-01-01

108

[Comparison of codon optimizations of cry1Ah1 gene in rice].  

PubMed

cry1Ah1, one of holo-type cry genes, cloned in this laboratory from Bacillus thuringiensis strain has been patented in China, and it encoded a protein with strong insecticidal activity against certain lepidopteran insect pests, such as Chilo suppressalis. cry1Ah1 gene is exhibiting good application prospects. In order to improve the expression level of cry1Ah1 gene in rice, and investigate the effect of codon usage preference of gene expression, we designed five different optimized schemes for cry1Ah1 insecticidal critical fragment in accordance with bias of rice codon, to improve G+C content, removed the shear signal and unstable factors. Optimized cry1Ah1 genes were transformed into Escherichia coli Rosetta (DE3) respectively, and 65 kDa polypeptides was expressed normally in inclusion body separately. All of these expressed polypeptides showed insecticidal activity against 2nd-instar larvae of Plutella xylostella and neonate of Chilo suppressalis. After transformation with modified cry1Ah1 genes into Var nippobare, the transgenic rice seedlings were detected by PCR, the positive rate containing target gene was more than 87%. Afterwards, the results of real-time RT-PCR and ELISA assay indicated that the highest expression level of five modified cry1Ah1 genes was that using the highest frequent codons. Average expression amount of Cry1Ah1 polypeptides was 0.104% of total soluble proteins from the positive transgenic rice. PMID:23311133

Zhou, Zongliang; Lin, Zhimin; Geng, Lili; Su, Jun; Shu, Changlong; Wang, Feng; Zhu, Yanming; Zhang, Jie

2012-10-01

109

Multiple Effects of Codon Usage Optimization on Expression and Immunogenicity of DNA Candidate Vaccines Encoding the Human Immunodeficiency Virus Type 1 Gag Protein  

PubMed Central

We have analyzed the influence of codon usage modifications on the expression levels and immunogenicity of DNA vaccines, encoding the human immunodeficiency virus type 1 (HIV-1) group-specific antigen (Gag). In the presence of Rev, an expression vector containing the wild-type (wt) gag gene flanked by essential cis-acting sites such as the 5?-untranslated region and 3?-Rev response element supported substantial Gag protein expression and secretion in human H1299 and monkey COS-7 cells. However, only weak Gag production was observed from the murine muscle cell line C2C12. In contrast, optimization of the Gag coding sequence to that of highly expressed mammalian genes (syngag) resulted in an obvious increase in the G+C content and a Rev-independent expression and secretion of Gag in all tested mammalian cell lines, including murine C2C12 muscle cells. Mice immunized intramuscularly with the syngag plasmid showed Th1-driven humoral and cellular responses that were substantially higher than those obtained after injection of the Rev-dependent wild-type (wt) gag vector system. In contrast, intradermal immunization of both wt gag and syngag vector systems with the particle gun induced a Th2-biased antibody response and no cytotoxic T lymphocytes. Deletion analysis demonstrated that the CpG motifs generated within syngag by codon optimization do not contribute significantly to the high immunogenicity of the syngag plasmid. Moreover, low doses of coadministered stimulatory phosphorothioate oligodeoxynucleotides (ODNs) had only a weak effect on antibody production, whereas at higher doses immunostimulatory and nonstimulatory ODNs showed a dose-dependent suppression of humoral responses. These results suggest that increased Gag expression, rather than modulation of CpG-driven vector immunity, is responsible for the enhanced immunogenicity of the syngag DNA vaccine.

Deml, Ludwig; Bojak, Alexandra; Steck, Stephanie; Graf, Marcus; Wild, Jens; Schirmbeck, Reinhold; Wolf, Hans; Wagner, Ralf

2001-01-01

110

High-Level Expression in Mammalian Cells of Recombinant House Dust Mite Allergen ProDer p 1 with Optimized Codon Usage  

Microsoft Academic Search

Background: The major house dust mite allergen Der p 1 is associated with allergic diseases such as asthma. Production of recombinant Der p 1 was previously attempted, but with limited success. The present study describes the expression of recombinant (rec) ProDer p 1, a recombinant precursor form of Der p 1, in CHO cells. Methods: As optimization of the codon

Marc Massaer; Pasqualina Mazzu; Michèle Haumont; Mauro Magi; Véronique Daminet; Alex Bollen; Alain Jacquet

2001-01-01

111

The Comparison of Usage and Availability Measurements for Evaluating Resource Preference  

Microsoft Academic Search

Abstract. Modern ecological research often involves the comparison of the usage of habitat types or food items to the availability of those resources to the animal. Widely used methods of determining preference from measurements of usage and availability depend critically on the array of components

Douglas H. Johnson

1980-01-01

112

RAR-beta4, a Retinoic Acid Receptor Isoform is Generated from RAR-beta2 by Alternative Splicing and Usage of a CUG Initiator Codon  

Microsoft Academic Search

An isoform of retinoic acid receptor beta, RAR-beta4, has been identified. RAR-beta 4 is expressed under the control of the same retinoic acid-responsive promoter as RAR-beta2. RAR-beta4, which is generated by alternative splicing from the same primary transcripts as RAR-beta2, is initiated by a non-AUG codon, CUG. The amino acid sequence of RAR-beta4 in regions B-F is identical to that

Sunil Nagpal; Arthur Zelent; Pierre Chambon

1992-01-01

113

Negative Consequences of Undergraduate Alcohol Usage: A Multivariate Gender Comparison.  

ERIC Educational Resources Information Center

This study examined whether female undergraduate students who share with male undergraduates similar demographics, perceptions, and alcohol use locations, also share similar alcohol usage patterns, negative consequences, and predictors for both. Secondary analysis was conducted using 1992 and 1993 U.S. Department of Education Core Survey data…

Robinson, Leonald D.

114

In Arabidopsis thaliana codon volatility scores reflect GC3 composition rather than selective pressure  

PubMed Central

Background Synonymous codon usage bias has typically been correlated with, and attributed to translational efficiency. However, there are other pressures on genomic sequence composition that can affect codon usage patterns such as mutational biases. This study provides an analysis of the codon usage patterns in Arabidopsis thaliana in relation to gene expression levels, codon volatility, mutational biases and selective pressures. Results We have performed synonymous codon usage and codon volatility analyses for all genes in the A. thaliana genome. In contrast to reports for species from other kingdoms, we find that neither codon usage nor volatility are correlated with selection pressure (as measured by dN/dS), nor with gene expression levels on a genome wide level. Our results show that codon volatility and usage are not synonymous, rather that they are correlated with the abundance of G and C at the third codon position (GC3). Conclusions Our results indicate that while the A. thaliana genome shows evidence for synonymous codon usage bias, this is not related to the expression levels of its constituent genes. Neither codon volatility nor codon usage are correlated with expression levels or selective pressures but, because they are directly related to the composition of G and C at the third codon position, they are the result of mutational bias. Therefore, in A. thaliana codon volatility and usage do not result from selection for translation efficiency or protein functional shift as measured by positive selection.

2012-01-01

115

Rare codon content affects the solubility of recombinant proteins in a codon bias-adjusted Escherichia coli strain  

Microsoft Academic Search

BACKGROUND: The expression of heterologous proteins in Escherichia coli is strongly affected by codon bias. This phenomenon occurs when the codon usage of the mRNA coding for the foreign protein differs from that of the bacterium. The ribosome pauses upon encountering a rare codon and may detach from the mRNA, thereby the yield of protein expression is reduced. Several bacterial

Germán L Rosano; Eduardo A Ceccarelli

2009-01-01

116

A Cross-Cultural Comparison of UCC usage in Korea and U.S.A  

Microsoft Academic Search

Integrating the technology acceptance model (TAM) and the pleasure-arousal-dominance (PAD) mode, this study aims at identifying the determinants of the favorable user created contents (UCC) usage. This study further attempts a cross cultural comparison on collectivistic and individualistic cultures, Korea and the U.S.A., respectively. The study shows the significant effects of usefulness and ease of use, which are critical variables

Sora Kang; Yoo-jung Kim; Hyunju Lee

2009-01-01

117

A General Model of Codon Bias Due to GC Mutational Bias  

Microsoft Academic Search

BackgroundIn spite of extensive research on the effect of mutation and selection on codon usage, a general model of codon usage bias due to mutational bias has been lacking. Because most amino acids allow synonymous GC content changing substitutions in the third codon position, the overall GC bias of a genome or genomic region is highly correlated with GC3, a

Gareth A. Palidwor; Theodore J. Perkins; Xuhua Xia; Dov Joseph Stekel

2010-01-01

118

Site-Specific Codon Bias in Bacteria  

PubMed Central

Sequences of the gapA and ompA genes from 10 genera of enterobacteria have been analyzed. There is strong bias in codon usage, but different synonymous codons are preferred at different sites in the same gene. Site-specific preference for unfavored codons is not confined to the first 100 codons and is usually manifest between two codons utilizing the same tRNA. Statistical analyses, based on conclusions reached in an accompanying paper, show that the use of an unfavored codon at a given site in different genera is not due to common descent and must therefore be caused either by sequence-specific mutation or sequence-specific selection. Reasons are given for thinking that sequence-specific mutation cannot be responsible. We are unable to explain the preference between synonymous codons ending in C or T, but synonymous choice between A and G at third sites is largely explained by avoidance of AG-G (where the hyphen indicates the boundary between codons). We also observed that the preferred codon for proline in Enterobacter cloacea has changed from CCG to CCA.

Smith, J. M.; Smith, N. H.

1996-01-01

119

Rare codons regulate KRas oncogenesis.  

PubMed

Oncogenic mutations in the small Ras GTPases KRas, HRas, and NRas render the proteins constitutively GTP bound and active, a state that promotes cancer. Ras proteins share ~85% amino acid identity, are activated by and signal through the same proteins, and can exhibit functional redundancy. Nevertheless, manipulating expression or activation of each isoform yields different cellular responses and tumorigenic phenotypes, even when different ras genes are expressed from the same locus. We now report a novel regulatory mechanism hardwired into the very sequence of RAS genes that underlies how such similar proteins impact tumorigenesis differently. Specifically, despite their high sequence similarity, KRAS is poorly translated compared to HRAS due to enrichment in genomically underrepresented or rare codons. Converting rare to common codons increases KRas expression and tumorigenicity to mirror that of HRas. Furthermore, in a genome-wide survey, similar gene pairs with opposing codon bias were identified that not only manifest dichotomous protein expression but also are enriched in key signaling protein classes and pathways. Thus, synonymous nucleotide differences affecting codon usage account for differences between HRas and KRas expression and function and may represent a broader regulation strategy in cell signaling. PMID:23246410

Lampson, Benjamin L; Pershing, Nicole L K; Prinz, Joseph A; Lacsina, Joshua R; Marzluff, William F; Nicchitta, Christopher V; MacAlpine, David M; Counter, Christopher M

2012-12-13

120

Conserved codon composition of ribosomal protein coding genes in Escherichia coli, Mycobacterium tuberculosis and Saccharomyces cerevisiae: lessons from supervised machine learning in functional genomics  

PubMed Central

Genomics projects have resulted in a flood of sequence data. Functional annotation currently relies almost exclusively on inter-species sequence comparison and is restricted in cases of limited data from related species and widely divergent sequences with no known homologs. Here, we demonstrate that codon composition, a fusion of codon usage bias and amino acid composition signals, can accurately discriminate, in the absence of sequence homology information, cytoplasmic ribosomal protein genes from all other genes of known function in Saccharomyces cerevisiae, Escherichia coli and Mycobacterium tuberculosis using an implementation of support vector machines, SVMlight. Analysis of these codon composition signals is instructive in determining features that confer individuality to ribosomal protein genes. Each of the sets of positively charged, negatively charged and small hydrophobic residues, as well as codon bias, contribute to their distinctive codon composition profile. The representation of all these signals is sensitively detected, combined and augmented by the SVMs to perform an accurate classification. Of special mention is an obvious outlier, yeast gene RPL22B, highly homologous to RPL22A but employing very different codon usage, perhaps indicating a non-ribosomal function. Finally, we propose that codon composition be used in combination with other attributes in gene/protein classification by supervised machine learning algorithms.

Lin, Kui; Kuang, Yuyu; Joseph, Jeremiah S.; Kolatkar, Prasanna R.

2002-01-01

121

Increased incidence of rare codon clusters at 5' and 3' gene termini:implications for function  

PubMed Central

Background The process of translation can be affected by the use of rare versus common codons within the mRNA transcript. Results Here, we show that rare codons are enriched at the 5' and 3' termini of genes from E. coli and other prokaryotes. Genes predicted to be secreted show significant enrichment in 5' rare codon clusters, but not 3' rare codon clusters. Surprisingly, no correlation between 5' mRNA structure and rare codon usage was observed. Conclusions Potential functional roles for the enrichment of rare codons at terminal positions are explored.

2010-01-01

122

Intercodon dinucleotides affect codon choice in plant genes.  

PubMed

In this work, 710 CDSs corresponding to over 290 000 codons equally distributed between Brassica napus, Arabidopsis thaliana, Lycopersicon esculentum, Nicotiana tabacum, Pisum sativum, Glycine max, Oryza sativa, Triticum aestivum, Hordeum vulgare and Zea mays were considered. For each amino acid, synonymous codon choice was determined in the presence of A, G, C or T as the initial nucleotide of the subsequent triplet; data were statistically analysed under the hypothesis of an independent assortment of codons. In 33.4% of cases, a frequency significantly (P: = 0.01) different from that expected was recorded. This was mainly due to a pervasive intercodon TpA and CpG deficiency. As a general rule, intercodon TpAs and CpGs were preferably replaced by CpAs and TpGs, respectively. In several instances, codon frequencies were also modified to avoid homotetramer and homotrimer formation, to reduce intercodon ApCs downstream (1,2) GG or AG dinucleotides, as well as to increase GpA or ApG intercodons under certain contexts. Since TpA, CpG and homotetra(tri)mer deficiency directly or indirectly accounted for 77% of significant variation in the codon frequency, it can be concluded that codon usage mirrors precise needs at the DNA structure level. Plant species exhibited a phylogenetically-related adaptation to structural constraints. Codon usage flexibility was reflected in strikingly different arrays of optimum codons for probe design. PMID:10954603

De Amicis, F; Marchetti, S

2000-09-01

123

Analysis of KRAS Mutations of Exon 2 Codons 12 and 13 by SNaPshot Analysis in Comparison to Common DNA Sequencing  

PubMed Central

Due to the call for fast KRAS mutation status analysis for treatment of patients with monoclonal antibodies for metastatic colorectal cancer, sensitive, economic, and easily feasible methods are required. Under this aspect, the sensitivity and specificity of the SNaPshot analysis in comparison to the commonly used DNA sequencing was checked. We examined KRAS mutations in exon 2 codons 12 and 13 with DNA sequencing and SNaPshot analysis in 100 formalin-fixed paraffin-embedded tumor tissue samples of pancreatic carcinoma, colorectal carcinoma, and nonsmall cell lung cancer specimens of the primary tumor or metastases. 40% of these samples demonstrated mutated KRAS genes using sequencing and SNaPshot-analysis; additional five samples (45/100) were identified only with the SNaPshot. KRAS mutation detection is feasible with the reliable SNaPshot analysis method. The more frequent mutation detection by the SNaPshot analysis shows that this method has a high probability of accuracy in the detection of KRAS mutations compared to sequencing.

Zinsky, Rica; Bolukbas, Servet; Bartsch, Holger; Schirren, Joachim; Fisseler-Eckhoff, Annette

2010-01-01

124

Evolutionary Lability of Context-Dependent Codon Bias in Bacteria  

Microsoft Academic Search

.   In bacteria, synonymous codon usage can be considerably affected by base composition at neighboring sites. Such context-dependent\\u000a biases may be caused by either selection against specific nucleotide motifs or context-dependent mutation biases. Here we\\u000a consider the evolutionary conservation of context-dependent codon bias across 11 completely sequenced bacterial genomes. In\\u000a particular, we focus on two contextual biases previously identified in

Gilean A. T. McVean; Gregory D. D. Hurst

2000-01-01

125

First impression versus extended usage: a comparison of product testing methodologies for perfume.  

PubMed

Synopsis In the fine fragrance industry, unlike many other fast moving consumer goods (fmcg) industries, systematic consumer product-testing has usually been conspicuous by its absence. The reasons are varied, including perfume's own traditions rooted in fashion rather than in marketing, the reluctance of perfumers to see their creations tested, the frequently (and perhaps, surprisingly) short lead times accorded for new product development and, of course, costs. When consumer product-testing is carried out, it is often limited for these same reasons, to 'sniff-testing', which, in the perfume industry, is equivalent to 'first impression' testing. This paper suggests that such sniff-testing may not only be unreliable, but perhaps more unreliable for the perfume category than has been realized hitherto. Reference is made to two consumer research studies on perfume, a qualitative project in France, followed by a quantitative exercise in the UK. A comparison is made between in-home test and sniff-test results for the same set of perfumes, which illustrates the limitations of sniff-testing in general, and the misleading results that it may produce, in particular. A major implication is that perfume is one product category which should be tested in extended usage, and not just for 'first impressions'. Résumé Dans l'industrie de la parfumerie fine, contrairement aux autres industries de produits de grande consommation, les tests consommateurs systématiques sont rarement utilisés. Les raisons sont diverses; les traditions propres du parfum tournées vers la mode plutôt que vers le marketing, le refus des parfumeurs de voir leurs créations subir des tests, les délais étonnamment courts pour le développement d'un nouveau produit et, bien sûr, le coût. Lorsqu'un test consommateurs est effectué, il se résume généralement pour ces mêmes raisons, en un test 'sniff', ce qui, dans l'industrie du parfum équivaut à un test de 'première impression'. Cet article montre que ces tests 'sniff' sont encore moins fiables pour le parfum que l'on avait pensé jusqu'à maintenant. Il est fait référence à deux tests consommateurs sur le parfum, un projet qualitatif en France, suivi par un exercice quantitatif effectué en Grande Bretagne. La comparaison entre les tests réalisés à domicile d'une part, et en sale d'autre part, montre que, pour les mêmes parfums, les résultats obtenus peuvent être erronés. Une des conclusions principales est que le parfum est un produit qui devrait être testé sur une longue période et non pas sur une première impression. PMID:19272121

Shalofsky, I

1993-04-01

126

Codon Optimization of Gene Fragments Encoding Plasmodium falciparum Merzoite Proteins Enhances DNA Vaccine Protein Expression and Immunogenicity in Mice  

Microsoft Academic Search

In contrast to conventional vaccines, DNA and other subunit vaccines exclusively utilize host cell molecules for transcription and translation of proteins. The adenine plus thymine content of Plasmodium falciparum gene sequences (80%) is much greater than that of Homo sapiens (59%); consequently, codon usage is markedly different. We hypothesized that modifying codon usage of P. falciparum genes encoded by DNA

DAVID L. NARUM; SANJAI KUMAR; WILLIAM O. ROGERS; STEVEN R. FUHRMANN; HONG LIANG; MIRANDA OAKLEY; ALEM TAYE; B. KIM LEE SIM; STEPHEN L. HOFFMAN

2001-01-01

127

Comparison of Public Relations and News Professionals’ Usage of Social Media in Communication Relationships  

Microsoft Academic Search

Professionals in the areas of public relations and news adopt social media extensively in their respective disciplines. Thus the focus of this study is to ascertain how social media was used in professional communication. A questionnaire sent to both journalists and public relations practitioners was distributed via email. The questions focused on professional usage (minutes and hours), identifying both professional

Kathy Stalbaum

2011-01-01

128

Lecture Attendance and Web Based Lecture Technologies: A Comparison of Student Perceptions and Usage Patterns  

ERIC Educational Resources Information Center

|This paper investigates the impact of web based lecture recordings on learning and attendance at lectures. Student opinions regarding the perceived value of the recordings were evaluated in the context of usage patterns and final marks, and compared with attendance data and student perceptions regarding the usefulness of lectures. The…

von Konsky, Brian R.; Ivins, Jim; Gribble, Susan J.

2009-01-01

129

Web acceptance and usage model: A comparison between goal-directed and experiential web users  

Microsoft Academic Search

Purpose – To analyse the web acceptance and usage between goal-directed users and experiential users, incorporating intrinsic motives to improve the particular and explanatory TAM (technology acceptance model) value – traditionally related to extrinsic motives. Design\\/methodology\\/approach – A survey instrument was used to gather data to test the relationships shown in the research model. Data were collected from a sample

Manuel J. Sánchez-franco; José L. Roldán

2005-01-01

130

Codon populations in single-stranded whole human genome DNA Are fractal and fine-tuned by the Golden Ratio 1.618  

Microsoft Academic Search

This new bioinformatics research bridges Genomics and Mathematics. We propose a universal “Fractal Genome Code Law”: The frequency\\u000a of each of the 64 codons across the entire human genome is controlled by the codon’s position in the Universal Genetic Code\\u000a table. We analyze the frequency of distribution of the 64 codons (codon usage) within single-stranded DNA sequences. Concatenating\\u000a 24 Human

Jean-Claude Perez

2010-01-01

131

Medication usage among young adult women: a comparison between Sweden, the USA, and Greece.  

PubMed

This study evaluated whether or not medication usage among young adult women differed across three countries. An additional aim was to evaluate the association between medication use and sociodemographic factors and exercise habits. A sample of 1098 young adult women were selected in Sweden, the USA, and Greece. Consistent medication usage by young adult women in the three countries related to oral contraceptives and vitamins; nevertheless, there were differences. The main differences were found in the use of laxatives, iron supplements, analgesics, antidepressants, and antacid medication. The most outstanding differences were the frequent use of laxatives in Sweden and vitamins in the USA. Different association patterns were found between medication use and culture, sociodemographic factors, and exercise. The assessment of medication use among young adult women can be performed very easily and provides an immediate indication of their well-being and needs for preventative care. PMID:18257825

Lidell, Evy; Luepker, Russell; Baigi, Amir; Lagiou, Areti; Hildingh, Cathrine

2008-03-01

132

Tandem Stop Codons in Ciliates That Reassign Stop Codons  

Microsoft Academic Search

Tandem stop codons are extra stop codons hypothesized to be present downstream of genes to act as a backup in case of read-through\\u000a of the real stop codon. Although seemingly absent from Escherichia coli, recent studies have confirmed the presence of such codons in yeast. In this paper we will analyze the genomes of two ciliate\\u000a species—Paramecium tetraurelia and Tetrahymena

Marie Adachi; Andre R. O. Cavalcanti

2009-01-01

133

The Relation of Codon Bias to Tissue-Specific Gene Expression in Arabidopsis thaliana  

PubMed Central

The codon composition of coding sequences plays an important role in the regulation of gene expression. Herein, we report systematic differences in the usage of synonymous codons among Arabidopsis thaliana genes that are expressed specifically in distinct tissues. Although we observed that both regionally and transcriptionally associated mutational biases were associated significantly with codon bias, they could not explain the observed differences fully. Similarly, given that transcript abundances did not account for the differences in codon usage, it is unlikely that selection for translational efficiency can account exclusively for the observed codon bias. Thus, we considered the possible evolution of codon bias as an adaptive response to the different abundances of tRNAs in different tissues. Our analysis demonstrated that in some cases, codon usage in genes that were expressed in a broad range of tissues was influenced primarily by the tissue in which the gene was expressed maximally. On the basis of this finding we propose that genes that are expressed in certain tissues might show a tissue-specific compositional signature in relation to codon usage. These findings might have implications for the design of transgenes in relation to optimizing their expression.

Camiolo, Salvatore; Farina, Lorenzo; Porceddu, Andrea

2012-01-01

134

764. RNA and Codon Optimized HIV Candidate Vaccines - from Bench to Clinical Trials  

Microsoft Academic Search

As recently demonstrated, extensive codon-usage modifications increased the overall GC content of late HIV transcripts by almost 30%, enhanced the nuclear stability of viral RNAs and resulted in a constitutive export of these RNAs into the cytoplasm. Besides, codon-usage modifications tremendously supported Rev-independent viral gene expression and significantly increased the safety of related vaccine constructs by reducing the risk for

Ralf Wagner; Petra Mooij; Sunita Balla; Jens Wild; Kurt Bieler; Hans Wolf; Frank Notka; Jonathan Heeney; Giuseppe Pantaleo

2005-01-01

135

[Analysis of codon use features of CBF gene in Camellia sinensis].  

PubMed

CBF (C-repeat-binding factor) transcription factor exists widely in all kinds of plants. It is an important regulative factor in the process of plant resistance adversity. In this paper, Camellia sinensis CBF1 gene sequence was analyzed by Codon W, CHIPS, and CUSP programs online, and then compared with C. sinensis genes, genomes in other species, and CBF genes from 39 plant species. It is important to identify the codon usage of CsCBF1 gene and select appropriate expression systems. The results showed that CsCBF1 gene and selected 70 C. sinensis genes had distinct usage differences. CsCBF1 gene was bias toward the synonymous codons with G and C at the third codon position, but 70 C. sinensis genes were bias toward the synonymous codons with A and T. The differences in codon usage frequency between CsCBF1 gene and dicotyledons such as Arabidopsis thaliana and Nicotiana tobacum were less than monocotyledons such as wheat (Triticum aestivum) and corn (Zea mays). Therefore, A. thaliana and N. tobacum expression systems may be more suitable for the expression of CsCBF1 gene. The analysis results of CBF genes from 40 plant species also showed that most of the CBF genes were bias toward the synonymous codons with G and C at the third codon position. The reason of this phenomenon is possible due to special functions of these genes. PMID:23262110

Guo, Xiu-Li; Wang, Yu; Yang, Lu-Cheng; Ding, Zhao-Tang

2012-12-01

136

The Levels of Speech Usage Rating Scale: Comparison of Client Self-Ratings with Speech Pathologist Ratings  

ERIC Educational Resources Information Center

|Background: The term "speech usage" refers to what people want or need to do with their speech to fulfil the communication demands in their life roles. Speech-language pathologists (SLPs) need to know about clients' speech usage to plan appropriate interventions to meet their life participation goals. The Levels of Speech Usage is a categorical…

Gray, Christina; Baylor, Carolyn; Eadie, Tanya; Kendall, Diane; Yorkston, Kathryn

2012-01-01

137

Codon preference optimization increases heterologous PEDF expression.  

PubMed

Pigment epithelium-derived factor (PEDF) is widely known for its neurotrophic and antiangiogenic functions. Efficacy studies of PEDF in animal models are limited because of poor heterologous protein yields. Here, we redesigned the human PEDF gene to preferentially match codon frequencies of E coli without altering the amino acid sequence. Following de novo synthesis, codon optimized PEDF (coPEDF) and the wtPEDF genes were cloned into pET32a containing a 5' thioredoxin sequence (Trx) and the recombinant Trx-coPEDF or Trx-wtPEDF fusion constructs expressed in native and two tRNA augmented E coli hosts - BL21-CodonPlus(DE3)-RIL and BL21-CodonPlus(DE3)-RP, carrying extra copies of tRNAarg,ile,leu and tRNAarg,pro genes, respectively. Trx-PEDF fusion proteins were isolated using Ni-NTA metal affinity chromatography and PEDF purified after cleavage with factor X?. Protein purity and identity were confirmed by western blot, MALDI-TOF, and UV/CD spectral analyses. Expression of the synthetic gene was ?3.4 fold greater (212.7 mg/g; 62.1 mg/g wet cells) and purified yields ?4 fold greater (41.1 mg/g; 11.3 mg/g wet cell) than wtPEDF in the native host. A small increase in expression of both genes was observed in hosts supplemented with rare tRNA genes compared to the native host but expression of coPEDF was ?3 fold greater than wtPEDF in both native and codon-bias-adjusted E coli strains. ?Gs at -3 to +50 of the Trx site of both fusion genes were -3.9 kcal/mol. Functionally, coPEDF was equally as effective as wtPEDF in reducing oxidative stress, promoting neurite outgrowth, and blocking endothelial tube formation. These findings suggest that while rare tRNA augmentation and mRNA folding energies can significantly contribute to increased protein expression, preferred codon usage, in this case, is advantageous to translational efficiency of biologically active PEDF in E coli. This strategy will undoubtedly fast forward studies to validate therapeutic utility of PEDF in vivo. PMID:21152082

Gvritishvili, Anzor G; Leung, Kar Wah; Tombran-Tink, Joyce

2010-11-30

138

Codon Preference Optimization Increases Heterologous PEDF Expression  

PubMed Central

Pigment epithelium-derived factor (PEDF) is widely known for its neurotrophic and antiangiogenic functions. Efficacy studies of PEDF in animal models are limited because of poor heterologous protein yields. Here, we redesigned the human PEDF gene to preferentially match codon frequencies of E coli without altering the amino acid sequence. Following de novo synthesis, codon optimized PEDF (coPEDF) and the wtPEDF genes were cloned into pET32a containing a 5? thioredoxin sequence (Trx) and the recombinant Trx-coPEDF or Trx-wtPEDF fusion constructs expressed in native and two tRNA augmented E coli hosts - BL21-CodonPlus(DE3)-RIL and BL21-CodonPlus(DE3)-RP, carrying extra copies of tRNAarg,ile,leu and tRNAarg,pro genes , respectively. Trx-PEDF fusion proteins were isolated using Ni-NTA metal affinity chromatography and PEDF purified after cleavage with factor X?. Protein purity and identity were confirmed by western blot, MALDI-TOF, and UV/CD spectral analyses. Expression of the synthetic gene was ?3.4 fold greater (212.7 mg/g; 62.1 mg/g wet cells) and purified yields ?4 fold greater (41.1 mg/g; 11.3 mg/g wet cell) than wtPEDF in the native host. A small increase in expression of both genes was observed in hosts supplemented with rare tRNA genes compared to the native host but expression of coPEDF was ?3 fold greater than wtPEDF in both native and codon-bias-adjusted E coli strains. ?Gs at ?3 to +50 of the Trx site of both fusion genes were ?3.9 kcal/mol. Functionally, coPEDF was equally as effective as wtPEDF in reducing oxidative stress, promoting neurite outgrowth, and blocking endothelial tube formation. These findings suggest that while rare tRNA augmentation and mRNA folding energies can significantly contribute to increased protein expression, preferred codon usage, in this case, is advantageous to translational efficiency of biologically active PEDF in E coli. This strategy will undoubtedly fast forward studies to validate therapeutic utility of PEDF in vivo.

Gvritishvili, Anzor G.; Leung, Kar Wah; Tombran-Tink, Joyce

2010-01-01

139

Good Codons, Bad Transcript: Large Reductions in Gene Expression and Fitness Arising from Synonymous Mutations in a Key Enzyme  

PubMed Central

Biased codon usage in protein-coding genes is pervasive, whereby amino acids are largely encoded by a specific subset of possible codons. Within individual genes, codon bias is stronger at evolutionarily conserved residues, favoring codons recognized by abundant tRNAs. Although this observation suggests an overall pattern of selection for translation speed and/or accuracy, other work indicates that transcript structure or binding motifs drive codon usage. However, our understanding of codon bias evolution is constrained by limited experimental data on the fitness effects of altering codons in functional genes. To bridge this gap, we generated synonymous variants of a key enzyme-coding gene in Methylobacterium extorquens. We found that mutant gene expression, enzyme production, enzyme activity, and fitness were all significantly lower than wild-type. Surprisingly, encoding the gene using only rare codons decreased fitness by 40%, whereas an allele coded entirely by frequent codons decreased fitness by more than 90%. Increasing gene expression restored mutant fitness to varying degrees, demonstrating that the fitness disadvantage of synonymous mutants arose from a lack of beneficial protein rather than costs of protein production. Protein production was negatively correlated with the frequency of motifs with high affinity for the anti-Shine-Dalgarno sequence, suggesting ribosome pausing as the dominant cause of low mutant fitness. Together, our data support the idea that, although a particular set of codons are favored on average across a genome, in an individual gene selection can either act for or against codons depending on their local context.

Agashe, Deepa; Martinez-Gomez, N. Cecilia; Drummond, D. Allan; Marx, Christopher J.

2013-01-01

140

Codon usage and replicative strategies of hepatitis A virus  

Microsoft Academic Search

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has many biological characteristics that distinguish it from other members of the Picornaviridae family. Among these it is worth of note the need for an intact eIF4G factor for the initiation of translation and thus the inability to shut down host protein synthesis by a similar mechanism as in other picornaviruses.

Rosa M. Pintó; Lluis Aragonès; M. Isabel Costafreda; Enric Ribes; Albert Bosch

2007-01-01

141

Replicational and transcriptional selection on codon usage in Borrelia burgdorferi  

Microsoft Academic Search

With more than 10 fully sequenced, publicly available prokaryotic genomes, it is now becoming possible to gain useful insights into genome evolution. Before the genome era, many evolutionary processes were evaluated from limited data sets and evolutionary models were constructed on the basis of small amounts of evidence. In this paper, I show that genes on the Borrelia burgdorferi genome

JAMES O. MCINERNEY

1998-01-01

142

Synonymous Codon Choices in the Extremely GC-Poor Genome of Plasmodium falciparum: Compositional Constraints and Translational Selection  

Microsoft Academic Search

.   We have analyzed the patterns of synonymous codon preferences of the nuclear genes of Plasmodium falciparum, a unicellular parasite characterized by an extremely GC-poor genome. When all genes are considered, codon usage is strongly\\u000a biased toward A and T in third codon positions, as expected, but multivariate statistical analysis detects a major trend among\\u000a genes. At one end genes

Héctor Musto; Héctor Romero; Alejandro Zavala; Kamel Jabbari; Giorgio Bernardi

1999-01-01

143

DIFFUSION AND USAGE PATTERNS OF THE INTERNET IN KOREA AND JAPAN: A COMPARISON OF POLICY AND CUL TURAL FACTORS  

Microsoft Academic Search

This study compares two countries, Korea and Japan, in the diffusion and usage of the internet among college students. The two countries exhibit different strategies in adopting new IT, which influence the adoption rate of the internet. Although Korea and Japan are adjacent to each other and share somewhat similar values and culture, there are significant differences in the usage

BAE YOUNG

2004-01-01

144

Nonneutral GC3 and Retroelement Codon Mimicry in Phytophthora  

Microsoft Academic Search

Phytophthora is a genus entirely comprised of destructive plant pathogens. It belongs to the Stramenopila, a unique branch of eukaryotes,\\u000a phylogenetically distinct from plants, animals, or fungi. Phytophthora genes show a strong preference for usage of codons ending with G or C (high GC3). The presence of high GC3 in genes can be\\u000a utilized to differentiate coding regions from noncoding

Rays H. Y. Jiang; Francine Govers

2006-01-01

145

Functional Significance of an Evolutionarily Conserved Alanine (GCA) Resume Codon in tmRNA in Escherichia coli?  

PubMed Central

Occasionally, ribosomes stall on mRNAs prior to the completion of the polypeptide chain. In Escherichia coli and other eubacteria, tmRNA-mediated trans-translation is a major mechanism that recycles the stalled ribosomes. The tmRNA possesses a tRNA-like domain and a short mRNA region encoding a short peptide (ANDENYALAA in E. coli) followed by a termination codon. The first amino acid (Ala) of this peptide encoded by the resume codon (GCN) is highly conserved in tmRNAs in different species. However, reasons for the high evolutionary conservation of the resume codon identity have remained unclear. In this study, we show that changing the E. coli tmRNA resume codon to other efficiently translatable codons retains efficient functioning of the tmRNA. However, when the resume codon was replaced with the low-usage codons, its function was adversely affected. Interestingly, expression of tRNAs decoding the low-usage codon from plasmid-borne gene copies restored efficient utilization of tmRNA. We discuss why in E. coli, the GCA (Ala) is one of the best codons and why all codons in the short mRNA of the tmRNA are decoded by the abundant tRNAs.

Kapoor, Suman; Samhita, Laasya; Varshney, Umesh

2011-01-01

146

Codon preference in Dictyostelium discoideum.  

PubMed Central

Dictyostelium discoideum is of increasing interest as a model eukaryotic cell because its many attributes have recently been expanded to include improved genetic and biochemical manipulability. The ability to transform Dictyostelium using drug resistance as a selectable marker (1) and to gene target by high frequency homologous integration (2) makes this organism particularly useful for molecular genetic approaches to cell structure and function. Given this background, it becomes important to analyze the codon preference used in this organism. Dictyostelium displays a strong and unique overall codon preference. This preference varies between different coding regions and even varies between coding regions from the same gene family. The degree of codon preference may be correlated with expression levels but not with the developmental time of expression of the gene product. The strong codon preference can be applied to identify coding regions in Dictyostelium DNA and aid in the design of oligonucleotide probes for cloning Dictyostelium genes.

Warrick, H M; Spudich, J A

1988-01-01

147

Are stop codons recognized by base triplets in the large ribosomal RNA subunit?  

PubMed Central

The precise mechanism of stop codon recognition in translation termination is still unclear. A previously published study by Ivanov and colleagues proposed a new model for stop codon recognition in which 3-nucleotide Ter-anticodons within the loops of hairpin helices 69 (domain IV) and 89 (domain V) in large ribosomal subunit (LSU) rRNA recognize stop codons to terminate protein translation in eubacteria and certain organelles. We evaluated this model by extensive bioinformatic analysis of stop codons and their putative corresponding Ter-anticodons across a much wider range of species, and found many cases for which it cannot explain the stop codon usage without requiring the involvement of one or more of the eight possible noncomplementary base pairs. Involvement of such base pairs may not be structurally or thermodynamically damaging to the model. However, if, according to the model, Ter-anticodon interaction with stop codons occurs within the ribosomal A-site, the structural stringency which that site imposes on sense codon·tRNA anticodon interaction should also extend to stop codon·Ter-anticodon interactions. Moreover, with Ter-tRNA in place of an aminoacyl-tRNA, for each of the various Ter-anticodons there is a sense codon that can interact with it preferentially by complementary and wobble base-pairing. Both these considerations considerably weaken the arguments put forth previously.

LIANG, HAN; LANDWEBER, LAURA F.; FRESCO, JACQUES R.

2005-01-01

148

Control of ribosome traffic by position-dependent choice of synonymous codons  

NASA Astrophysics Data System (ADS)

Messenger RNA (mRNA) encodes a sequence of amino acids by using codons. For most amino acids, there are multiple synonymous codons that can encode the amino acid. The translation speed can vary from one codon to another, thus there is room for changing the ribosome speed while keeping the amino acid sequence and hence the resulting protein. Recently, it has been noticed that the choice of the synonymous codon, via the resulting distribution of slow- and fast-translated codons, affects not only on the average speed of one ribosome translating the mRNA but also might have an effect on nearby ribosomes by affecting the appearance of ‘traffic jams’ where multiple ribosomes collide and form queues. To test this ‘context effect’ further, we here investigate the effect of the sequence of synonymous codons on the ribosome traffic by using a ribosome traffic model with codon-dependent rates, estimated from experiments. We compare the ribosome traffic on wild-type (WT) sequences and sequences where the synonymous codons were swapped randomly. By simulating translation of 87 genes, we demonstrate that the WT sequences, especially those with a high bias in codon usage, tend to have the ability to reduce ribosome collisions, hence optimizing the cellular investment in the translation apparatus. The magnitude of such reduction of the translation time might have a significant impact on the cellular growth rate and thereby have importance for the survival of the species.

Mitarai, Namiko; Pedersen, Steen

2013-10-01

149

English Usage in Hong Kong.  

ERIC Educational Resources Information Center

|Articles contained in this special issue on language usage in Hong Kong, particularly in the context of elementary and secondary education, include: "A Comparison of English Errors Made by Hong Kong Students and Those Made by Non-Native Learners of English Internationally" (David Bunton); "Errors in Guides to English Usage for Hong Kong Students"…

Bunton, David, Ed.; Green, Christopher F., Ed.

1991-01-01

150

Expected frequencies of codon use as a function of mutation rates and codon fitnesses  

Microsoft Academic Search

Summary A method is shown to determine the expected pattern of codon use for any given set of mutation rates between nucleotides and any set of fitnesses for the codons. If it is assumed that mutations to stop codons are lethal then those codons which can mutate in one step to a stop codon tend to be used less frequently.

G. B. Golding; C. Strobeck

1982-01-01

151

Computational codon optimization of synthetic gene for protein expression  

PubMed Central

Background The construction of customized nucleic acid sequences allows us to have greater flexibility in gene design for recombinant protein expression. Among the various parameters considered for such DNA sequence design, individual codon usage (ICU) has been implicated as one of the most crucial factors affecting mRNA translational efficiency. However, previous works have also reported the significant influence of codon pair usage, also known as codon context (CC), on the level of protein expression. Results In this study, we have developed novel computational procedures for evaluating the relative importance of optimizing ICU and CC for enhancing protein expression. By formulating appropriate mathematical expressions to quantify the ICU and CC fitness of a coding sequence, optimization procedures based on genetic algorithm were employed to maximize its ICU and/or CC fitness. Surprisingly, the in silico validation of the resultant optimized DNA sequences for Escherichia coli, Lactococcus lactis, Pichia pastoris and Saccharomyces cerevisiae suggests that CC is a more relevant design criterion than the commonly considered ICU. Conclusions The proposed CC optimization framework can complement and enhance the capabilities of current gene design tools, with potential applications to heterologous protein production and even vaccine development in synthetic biotechnology.

2012-01-01

152

In vivo introduction of unpreferred synonymous codons into the Drosophila Adh gene results in reduced levels of ADH protein.  

PubMed Central

The evolution of codon bias, the unequal usage of synonymous codons, is thought to be due to natural selection for the use of preferred codons that match the most abundant species of isoaccepting tRNA, resulting in increased translational efficiency and accuracy. We examined this hypothesis by introducing 1, 6, and 10 unpreferred codons into the Drosophila alcohol dehydrogenase gene (Adh). We observed a significant decrease in ADH protein production with number of unpreferred codons, confirming the importance of natural selection as a mechanism leading to codon bias. We then used this empirical relationship to estimate the selection coefficient (s) against unpreferred synonymous mutations and found the value (s >or= 10(-5)) to be approximately one order of magnitude greater than previous estimates from population genetics theory. The observed differences in protein production appear to be too large to be consistent with current estimates of the strength of selection on synonymous sites in D. melanogaster.

Carlini, David B; Stephan, Wolfgang

2003-01-01

153

Evolution of optimal codon choices in the family Enterobacteriaceae.  

PubMed

The Enterobacteriaceae are a large family of Proteobacteria that include many well-known prokaryotic genera, such as Escherichia, Yersinia and Salmonella. The main ideas of synonymous codon usage (CU) evolution and translational selection have been deeply influenced by studies with these bacterial groups. In this work we report the analysis of the CU pattern of completely sequenced bacterial genomes that belong to the Enterobacteriaceae. The effect of selection in translation acting at the levels of speed and accuracy, and phylogenetic trends within this group are described. Preferred (optimal) codons were identified. The evolutionary dynamics of these codons were studied and following a Bayesian approach these preferences were traced back to the common ancestor of the family. We found that there is some level of variation in selection among the analysed micro-organisms that is probably associated with lineage-specific trends. The codon bias was largely conserved across the evolutionary time of the family in highly expressed genes and protein conserved regions, suggesting a major role of negative selection. In this sense, the results support the idea that the extant CU bias is finely tuned over the ancestral well-conserved pool of tRNAs. PMID:23288542

Iriarte, Andrés; Baraibar, Juan Diego; Romero, Héctor; Castro-Sowinski, Susana; Musto, Héctor

2013-01-03

154

A Comparison of the Influence of Social Factors and Technological Factors on Adoption and Usage of Knowledge Management Systems  

Microsoft Academic Search

Knowledge management strives for effective capture and application of organizational knowledge, a valuable resource imperative in sustaining an organization. In an effort to better achieve knowledge management initiatives, consideration of factors influencing adoption and usage of knowledge management systems are of great interest. Implementation of technological solutions are often considered organizational innovations subject to potential problems of resistance deeming social

Andrea J. Hester

2010-01-01

155

Adaptation to Different Human Populations by HIV1 Revealed by Codon-Based Analyses  

Microsoft Academic Search

Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that

Sergei L. Kosakovsky Pond; Simon D. W. Frost; Zehava Grossman; Michael B. Gravenor; Douglas D. Richman; Andrew J. Leigh Brown

2006-01-01

156

A Rev-Independent Human Immunodeficiency Virus Type 1 (HIV1)Based Vector That Exploits a Codon-Optimized HIV1 gag-pol Gene  

Microsoft Academic Search

The human immunodeficiency virus (HIV) genome is AU rich, and this imparts a codon bias that is quite different from the one used by human genes. The codon usage is particularly marked for the gag, pol, and env genes. Interestingly, the expression of these genes is dependent on the presence of the Rev\\/Rev-responsive element (RRE) regulatory system, even in contexts

EKATERINI KOTSOPOULOU; V. NARRY KIM; ALAN J. KINGSMAN; SUSAN M. KINGSMAN; KYRIACOS A. MITROPHANOUS

2000-01-01

157

Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus  

PubMed Central

Although the surface proteins of human influenza A virus evolve rapidly and continually produce antigenic variants, the internal viral genes acquire mutations very gradually. In this paper, we analyze the sequence evolution of three influenza A genes over the past two decades. We study codon usage as a discriminating signature of gene- and even residue-specific diversifying and purifying selection. Nonrandom codon choice can increase or decrease the effective local substitution rate. We demonstrate that the codons of hemagglutinin, particularly those in the antibody-combining regions, are significantly biased toward substitutional point mutations relative to the codons of other influenza virus genes. We discuss the evolutionary interpretation and implications of these biases for hemagglutinin's antigenic evolution. We also introduce information-theoretic methods that use sequence data to detect regions of recent positive selection and potential protein conformational changes.

Plotkin, Joshua B.; Dushoff, Jonathan

2003-01-01

158

Influence of Codon Bias on Heterologous Production of Human Papillomavirus Type 16 Major Structural Protein L1 in Yeast  

PubMed Central

Heterologous gene expression is dependent on multistep processes involving regulation at the level of transcription, mRNA turnover, protein translation, and posttranslational modifications. Codon bias has a significant influence on protein yields. However, sometimes it is not clear which parameter causes observed differences in heterologous gene expression as codon adaptation typically optimizes many sequence properties at once. In the current study, we evaluated the influence of codon bias on heterologous production of human papillomavirus type 16 (HPV-16) major structural protein L1 in yeast by expressing five variants of codon-modified open reading frames (OFRs) encoding HPV-16 L1 protein. Our results showed that despite the high toleration of various codons used throughout the length of the sequence of heterologously expressed genes in transformed yeast, there was a significant positive correlation between the gene's expression level and the degree of its codon bias towards the favorable codon usage. The HPV-16 L1 protein expression in yeast can be optimized by adjusting codon composition towards the most preferred codon adaptation, and this effect most probably is dependent on the improved translational elongation.

Norkiene, Milda; Gedvilaite, Alma

2012-01-01

159

Stop codon recognition in ciliates: Euplotes release factor does not respond to reassigned UGA codon  

PubMed Central

In eukaryotes, the polypeptide release factor 1 (eRF1) is involved in translation termination at all three stop codons. However, the mechanism for decoding stop codons remains unknown. A direct interaction of eRF1 with the stop codons has been postulated. Recent studies focus on eRF1 from ciliates in which some stop codons are reassigned to sense codons. Using an in vitro assay based on mammalian ribosomes, we show that eRF1 from the ciliate Euplotes aediculatus responds to UAA and UAG as stop codons and lacks the capacity to decipher the UGA codon, which encodes cysteine in this organism. This result strongly suggests that in ciliates with variant genetic codes eRF1 does not recognize the reassigned codons. Recent hypotheses describing stop codon discrimination by eRF1 are not fully consistent with the set of eRF1 sequences available so far and require direct experimental testing.

Kervestin, Stephanie; Frolova, Ludmila; Kisselev, Lev; Jean-Jean, Olivier

2001-01-01

160

Computational identification of rare codons of Escherichia coli based on codon pairs preference  

Microsoft Academic Search

BACKGROUND: Codon bias is believed to play an important role in the control of gene expression. In Escherichia coli, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not

Xianming Wu; Songfeng Wu; Dong Li; Jiyang Zhang; Lin Hou; Jie Ma; Wanlin Liu; Daming Ren; Yunping Zhu; Fuchu He

2010-01-01

161

Differences in codon bias cannot explain differences in translational power among microbes  

PubMed Central

Background Translational power is the cellular rate of protein synthesis normalized to the biomass invested in translational machinery. Published data suggest a previously unrecognized pattern: translational power is higher among rapidly growing microbes, and lower among slowly growing microbes. One factor known to affect translational power is biased use of synonymous codons. The correlation within an organism between expression level and degree of codon bias among genes of Escherichia coli and other bacteria capable of rapid growth is commonly attributed to selection for high translational power. Conversely, the absence of such a correlation in some slowly growing microbes has been interpreted as the absence of selection for translational power. Because codon bias caused by translational selection varies between rapidly growing and slowly growing microbes, we investigated whether observed differences in translational power among microbes could be explained entirely by differences in the degree of codon bias. Although the data are not available to estimate the effect of codon bias in other species, we developed an empirically-based mathematical model to compare the translation rate of E. coli to the translation rate of a hypothetical strain which differs from E. coli only by lacking codon bias. Results Our reanalysis of data from the scientific literature suggests that translational power can differ by a factor of 5 or more between E. coli and slowly growing microbial species. Using empirical codon-specific in vivo translation rates for 29 codons, and several scenarios for extrapolating from these data to estimates over all codons, we find that codon bias cannot account for more than a doubling of the translation rate in E. coli, even with unrealistic simplifying assumptions that exaggerate the effect of codon bias. With more realistic assumptions, our best estimate is that codon bias accelerates translation in E. coli by no more than 60% in comparison to microbes with very little codon bias. Conclusions While codon bias confers a substantial benefit of faster translation and hence greater translational power, the magnitude of this effect is insufficient to explain observed differences in translational power among bacterial and archaeal species, particularly the differences between slowly growing and rapidly growing species. Hence, large differences in translational power suggest that the translational apparatus itself differs among microbes in ways that influence translational performance.

Dethlefsen, Les; Schmidt, Thomas M

2005-01-01

162

Evaluation of Codon Biology in Citrus and Poncirus trifoliata Based on Genomic Features and Frame Corrected Expressed Sequence Tags  

PubMed Central

Citrus, as one of the globally important fruit trees, has been an object of interest for understanding genetics and evolutionary process in fruit crops. Meta-analyses of 19 Citrus species, including 4 globally and economically important Citrus sinensis, Citrus clementina, Citrus reticulata, and 1 Citrus relative Poncirus trifoliata, were performed. We observed that codons ending with A- or T- at the wobble position were preferred in contrast to C- or G- ending codons, indicating a close association with AT richness of Citrus species and P. trifoliata. The present study postulates a large repertoire of a set of optimal codons for the Citrus genus and P. trifoliata and demonstrates that GCT and GGT are evolutionary conserved optimal codons. Our observation suggested that mutational bias is the dominating force in shaping the codon usage bias (CUB) in Citrus and P. trifoliata. Correspondence analysis (COA) revealed that the principal axis [axis 1; COA/relative synonymous codon usage (RSCU)] contributes only a minor portion (?10.96%) of the recorded variance. In all analysed species, except P. trifoliata, Gravy and aromaticity played minor roles in resolving CUB. Compositional constraints were found to be strongly associated with the amino acid signatures in Citrus species and P. trifoliata. Our present analysis postulates compositional constraints in Citrus species and P. trifoliata and plausible role of the stress with GC3 and coevolution pattern of amino acid.

Ahmad, Touqeer; Sablok, Gaurav; Tatarinova, Tatiana V.; Xu, Qiang; Deng, Xiu-Xin; Guo, Wen-Wu

2013-01-01

163

CodonPhyML: Fast Maximum Likelihood Phylogeny Estimation under Codon Substitution Models  

PubMed Central

Markov models of codon substitution naturally incorporate the structure of the genetic code and the selection intensity at the protein level, providing a more realistic representation of protein-coding sequences compared with nucleotide or amino acid models. Thus, for protein-coding genes, phylogenetic inference is expected to be more accurate under codon models. So far, phylogeny reconstruction under codon models has been elusive due to computational difficulties of dealing with high dimension matrices. Here, we present a fast maximum likelihood (ML) package for phylogenetic inference, CodonPhyML offering hundreds of different codon models, the largest variety to date, for phylogeny inference by ML. CodonPhyML is tested on simulated and real data and is shown to offer excellent speed and convergence properties. In addition, CodonPhyML includes most recent fast methods for estimating phylogenetic branch supports and provides an integral framework for models selection, including amino acid and DNA models.

Gil, Manuel; Zoller, Stefan; Anisimova, Maria

2013-01-01

164

Codon-optimized fluorescent proteins designed for expression in low-GC gram-positive bacteria.  

PubMed

Fluorescent proteins have wide applications in biology. However, not all of these proteins are properly expressed in bacteria, especially if the codon usage and genomic GC content of the host organism are not ideal for high expression. In this study, we analyzed the DNA sequences of multiple fluorescent protein genes with respect to codons and GC content and compared them to a low-GC gram-positive bacterium, Bacillus anthracis. We found high discrepancies for cyan fluorescent protein (CFP), yellow fluorescent protein (YFP), and the photoactivatable green fluorescent protein (PAGFP), but not GFP, with regard to GC content and codon usage. Concomitantly, when the proteins were expressed in B. anthracis, CFP- and YFP-derived fluorescence was undetectable microscopically, a phenomenon caused not by lack of gene transcription or degradation of the proteins but by lack of protein expression. To improve expression in bacteria with low genomic GC contents, we synthesized a codon-optimized gfp and constructed optimized photoactivatable pagfp, cfp, and yfp, which were in contrast to nonoptimized genes highly expressed in B. anthracis and in another low-GC gram-positive bacterium, Staphylococcus aureus. Using optimized GFP as a reporter, we were able to monitor the activity of the protective antigen promoter of B. anthracis and confirm its dependence on bicarbonate and regulators present on virulence plasmid pXO1. PMID:19181829

Sastalla, Inka; Chim, Kannie; Cheung, Gordon Y C; Pomerantsev, Andrei P; Leppla, Stephen H

2009-01-30

165

Codon optimization of the calf prochymosin gene and its expression in Kluyveromyces lactis  

Microsoft Academic Search

Chymosin as an important industrial enzyme widely used in cheese manufacture. The yeast Kluyveromyces lactis is a promising host strain for expression of the chymosin gene. However, low yields (80 U\\/ml in shake flask cultures) were\\u000a obtained when the K. lactis strain GG799 was used to express chymosin. We hypothesized that the codon-usage bias of the host may have resulted in

Zhen FengLanwei; Lanwei Zhang; Xue Han; Yanhe Zhang

2010-01-01

166

The imprint of codons on protein structure.  

PubMed

The "central dogma" of biology outlines the unidirectional flow of interpretable data from genetic sequence to protein sequence. This has led to the idea that a protein's structure is dependent only on its amino acid sequence and not its genetic sequence. Recently, however, a more than transient link between the coding genetic sequence and the protein structure has become apparent. The two interact at the ribosome via the process of co-translational protein folding. Evidence for co-translational folding is growing rapidly, but the influence of codons on the protein structure attained is still highly contentious. It is theorised that the speed of codon translation modulates the time available for protein folding and hence the protein structure. Here, past and present research regarding synonymous codons and codon translation speed are reviewed within the context of protein structure attainment. PMID:21567957

Deane, Charlotte M; Saunders, Rhodri

2011-05-13

167

Combinatorial codon-based amino acid substitutions  

PubMed Central

Twenty Fmoc-protected trinucleotide phosphoramidites representing a complete set of codons for the natural amino acids were chemically synthesized for the first time. A pool of these reagents was incorporated into oligonucleotides at substoichiometric levels to generate two libraries of variants that randomly carry either few or many codon replacements on a region encoding nine amino acids of the bacterial enzyme TEM-1 ?-lactamase. Assembly of the libraries was performed in a completely automated mode through a simple modification of ordinary protocols. This technology eliminates codon redundancy, stop codons and enables complete exploration of sequence space for single, double and triple mutations throughout a protein region spanning several residues. Sequence analysis of many non-selected clones revealed a good incorporation of the trinucleotides, producing combinations of mutations quite different from those obtained using conventional degenerate oligonucleotides. Ceftazidime-selection experiments yielded several never before reported variants containing novel amino acid combinations in the ?-lactamase omega loop region.

Yanez, Jorge; Arguello, Martha; Osuna, Joel; Soberon, Xavier; Gaytan, Paul

2004-01-01

168

Context specific misreading of phenylalanine codons  

Microsoft Academic Search

It has previously been shown that the phenylalanine codon UUC encoding residue 8 of the Escherichia coli argI gene product, ornithine transcarbamylase, is misread as leucine at a high frequency during phenylalanine starvation. However, no misreading of the UUU encoding residue 3 was observed under these conditions. Using oligonucleotide-directed, site-specific mutagenesis, we have constructed mutants where these codons have been

James Precup; Amy K. Ulrich; Osha Roopnarine; Jack Parker

1989-01-01

169

Codon Preference Optimization Increases Heterologous PEDF Expression  

Microsoft Academic Search

Pigment epithelium-derived factor (PEDF) is widely known for its neurotrophic and antiangiogenic functions. Efficacy studies of PEDF in animal models are limited because of poor heterologous protein yields. Here, we redesigned the human PEDF gene to preferentially match codon frequencies of E coli without altering the amino acid sequence. Following de novo synthesis, codon optimized PEDF (coPEDF) and the wtPEDF

Anzor G. Gvritishvili; Kar Wah Leung; Joyce Tombran-Tink; Grzegorz Kudla

2010-01-01

170

Transfer RNA misidentification scrambles sense codon recoding.  

PubMed

Sense codon recoding is the basis for genetic code expansion with more than two different noncanonical amino acids. It requires an unused (or rarely used) codon, and an orthogonal tRNA synthetase:tRNA pair with the complementary anticodon. The Mycoplasma capricolum genome contains just six CGG arginine codons, without a dedicated tRNA(Arg) . We wanted to reassign this codon to pyrrolysine by providing M. capricolum with pyrrolysyl-tRNA synthetase, a synthetic tRNA with a CCG anticodon (${{\\rm tRNA}{{{\\rm Pyl}\\hfill \\atop {\\rm CCG}\\hfill}}}$), and the genes for pyrrolysine biosynthesis. Here we show that ${{\\rm tRNA}{{{\\rm Pyl}\\hfill \\atop {\\rm CCG}\\hfill}}}$ is efficiently recognized by the endogenous arginyl-tRNA synthetase, presumably at the anticodon. Mass spectrometry revealed that in the presence of ${{\\rm tRNA}{{{\\rm Pyl}\\hfill \\atop {\\rm CCG}\\hfill}}}$, CGG codons are translated as arginine. This result is not unexpected as most tRNA synthetases use the anticodon as a recognition element. The data suggest that tRNA misidentification by endogenous aminoacyl-tRNA synthetases needs to be overcome for sense codon recoding. PMID:24000185

Krishnakumar, Radha; Prat, Laure; Aerni, Hans-Rudolf; Ling, Jiqiang; Merryman, Chuck; Glass, John I; Rinehart, Jesse; Söll, Dieter

2013-09-02

171

Global mRNA Stability Is Not Associated with Levels of Gene Expression in Drosophila melanogaster But Shows a Negative Correlation with Codon Bias  

Microsoft Academic Search

A multitude of factors contribute to the regulation of gene expression in living cells. The relationship between codon usage bias and gene expression has been extensively studied, and it has been shown that codon bias may have adaptive significance in many unicellular and multicellular organisms. Given the central role of mRNA in post-transcriptional regulation, we hypothesize that mRNA stability is

Hans K. Stenøien; Wolfgang Stephan

2005-01-01

172

Gene Composer: database software for protein construct design, codon engineering, and gene synthesis  

PubMed Central

Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease error correction in combination with PIPE cloning. In a sister manuscript we present data on how Gene Composer designed genes and protein constructs can result in improved protein production for structural studies.

Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

2009-01-01

173

Alternative promoter usage and splicing of the human SCN5A gene contribute to transcript heterogeneity.  

PubMed

The sodium channel isoform Na(v)1.5 mediates sodium current, excitability, and electrical conduction in the human heart. Recent studies have indicated alternative splicing within the protein-coding portion of its gene, SCN5A, as a mechanism to generate diversity in Na(v)1.5 protein structure and function. In the present study we identified several novel SCN5A transcripts in human heart, displaying distinct 5?-untranslated regions but identical protein-coding sequences. These transcripts originated from the splicing of alternative exons 1 (designated 1A, 1B, 1C, and 1D) to the translational start codon-containing exon 2, and were preferentially expressed in the heart as compared to other tissues. Comparison of their expression level between adult and fetal heart demonstrated that exon 1C- and 1D-derived sequences were more prominent in adult than in fetal heart. Two new promoters (designated P2 and P3) for the SCN5A gene were identified and functionally characterized in myocardial- and nonmyocardial-derived cell lines. Translation of the transcript containing exon 1D-derived sequences proved to be significantly impaired in these cell lines, which could be restored by mutation of an upstream translational start codon. These results implicate the usage of alternative promoters and 5?-untranslated regions as new mechanisms in the regulation of human Na(v)1.5 expression. PMID:20618077

van Stuijvenberg, Leonie; Yildirim, Cansu; Kok, Bart G J M; van Veen, Toon A B; Varró, András; Winckels, Stephan K G; Vos, Marc A; Bierhuizen, Marti F A

2010-10-01

174

Most Used Codons per Amino Acid and per Genome in the Code of Man Compared to Other Organisms According to the Rotating Circular Genetic Code  

PubMed Central

My previous theoretical research shows that the rotating circular genetic code is a viable tool to make easier to distinguish the rules of variation applied to the amino acid exchange; it presents a precise and positional bio-mathematical balance of codons, according to the amino acids they codify. Here, I demonstrate that when using the conventional or classic circular genetic code, a clearer pattern for the human codon usage per amino acid and per genome emerges. The most used human codons per amino acid were the ones ending with the three hydrogen bond nucleotides: C for 12 amino acids and G for the remaining 8, plus one codon for arginine ending in A that was used approximately with the same frequency than the one ending in G for this same amino acid (plus *). The most used codons in man fall almost all the time at the rightmost position, clockwise, ending either in C or in G within the circular genetic code. The human codon usage per genome is compared to other organisms such as fruit flies (Drosophila melanogaster), squid (Loligo pealei), and many others. The biosemiotic codon usage of each genomic population or ‘Theme’ is equated to a ‘molecular language’. The C/U choice or difference, and the G/A difference in the third nucleotide of the most used codons per amino acid are illustrated by comparing the most used codons per genome in humans and squids. The human distribution in the third position of most used codons is a 12-8-2, C-G-A, nucleotide ending signature, while the squid distribution in the third position of most used codons was an odd, or uneven, distribution in the third position of its most used codons: 13-6-3, U-A-G, as its nucleotide ending signature. These findings may help to design computational tools to compare human genomes, to determine the exchangeability between compatible codons and amino acids, and for the early detection of incompatible changes leading to hereditary diseases.

Castro-Chavez, Fernando

2011-01-01

175

CpG Usage in RNA Viruses: Data and Hypotheses  

PubMed Central

CpG repression in RNA viruses has been known for decades, but a reasonable explanation has not yet been proposed to explain this phenomenon. In this study, we calculated the CpG odds ratio of all RNA viruses that have available genome sequences and analyzed the correlation with their genome polarity, base composition, synonymous codon usage, phylogenetic relationship, and host. The results indicated that the viral base composition, synonymous codon usage and host selection were the dominant factors that determined the CpG bias in RNA viruses. CpG usage variation between the different viral groups was caused by different combinations of these pressures, which also differed from each other in strength. The consistent under-representation of CpG usage in ?ssRNA viruses is determined predominantly by base composition, which may be a consequence of the U/A preferred mutation bias of ?ssRNA viruses, whereas the CpG usage of +ssRNA viruses is affected greatly by their hosts. As a result, most +ssRNA viruses mimic their hosts' CpG usage. Unbiased CpG usage in dsRNA viruses is most likely a result of their dsRNA genome, which allows the viruses to escape from the host-driven CpG elimination pressure. CpG was under-represented in all reverse-transcribing viruses (RT viruses), suggesting that DNA methylation is an important factor affecting the CpG usage of retroviruses. However, vertebrate-infecting RT viruses may also suffer host' CpG elimination pressure that also acts on +ssRNA viruses, which results in further under-representation of CpG in the vertebrate-infecting RT viruses.

Cheng, Xiaofei; Virk, Nasar; Chen, Wei; Ji, Shuqin; Ji, Shuxian; Sun, Yuqiang; Wu, Xiaoyun

2013-01-01

176

Hand gesture recognition by analysis of codons  

NASA Astrophysics Data System (ADS)

The problem of recognizing gestures from images using computers can be approached by closely understanding how the human brain tackles it. A full fledged gesture recognition system will substitute mouse and keyboards completely. Humans can recognize most gestures by looking at the characteristic external shape or the silhouette of the fingers. Many previous techniques to recognize gestures dealt with motion and geometric features of hands. In this thesis gestures are recognized by the Codon-list pattern extracted from the object contour. All edges of an image are described in terms of sequence of Codons. The Codons are defined in terms of the relationship between maxima, minima and zeros of curvature encountered as one traverses the boundary of the object. We have concentrated on a catalog of 24 gesture images from the American Sign Language alphabet (Letter J and Z are ignored as they are represented using motion) [2]. The query image given as an input to the system is analyzed and tested against the Codon-lists, which are shape descriptors for external parts of a hand gesture. We have used the Weighted Frequency Indexing Transform (WFIT) approach which is used in DNA sequence matching for matching the Codon-lists. The matching algorithm consists of two steps: 1) the query sequences are converted to short sequences and are assigned weights and, 2) all the sequences of query gestures are pruned into match and mismatch subsequences by the frequency indexing tree based on the weights of the subsequences. The Codon sequences with the most weight are used to determine the most precise match. Once a match is found, the identified gesture and corresponding interpretation are shown as output.

Ramachandra, Poornima; Shrikhande, Neelima

2007-09-01

177

Blepharisma Uses UAA as a termination codon  

Microsoft Academic Search

It has generally been assumed that all ciliates deviate from the universal genetic code by translating UAA and UAG as glutamine and using UGA as the sole termination codon. This assumption was based on sequence analyses of genes in four genera: Paramecium [1], Tetrahymena [2], Stylonychia [3], and Oxytrieha [4]. Recently, this view was challenged by the finding that in

A. Liang; K. Heckmann

1993-01-01

178

A common periodic table of codons and amino acids  

Microsoft Academic Search

A periodic table of codons has been designed where the codons are in regular locations. The table has four fields (16 places in each) one with each of the four nucleotides (A, U, G, C) in the central codon position. Thus, AAA (lysine), UUU (phenylalanine), GGG (glycine), and CCC (proline) were placed into the corners of the fields as the

J. C. Biro; B. Benyo; C. Sansom; Á Szlávecz; G Fördös; T Micsik; Z Benyó

2003-01-01

179

Codon usage limitation in the expression of HIV1 envelope glycoprotein  

Microsoft Academic Search

Background: The expression of both the env and gag gene products of human immunodeficiency virus type 1 (HIV-1) is known to be limited by cis elements in the viral RNA that impede egress from the nucleus and reduce the efficiency of translation. Identifying these elements has proven difficult, as they appear to be disseminated throughout the viral genome.Results Here, we

Jürgen Haas; Eun-Chung Park; Brian Seed

1996-01-01

180

Evidence of codon usage in the nearest neighbor spacing distribution of bases in bacterial genomes  

Microsoft Academic Search

Statistical analysis of whole genomic sequences usually assumes a homogeneous nucleotide density throughout the genome, an assumption that has been proved incorrect for several organisms since the nucleotide density is only locally homogeneous. To avoid giving a single numerical value to this variable property, we propose the use of spectral statistics, which characterizes the density of nucleotides as a function

M. F. Higareda; O. Geiger; L. Mendoza; R. A. Méndez-Sánchez

181

Differential Trends in the Codon Usage Patterns in HIV1 Genes  

Microsoft Academic Search

Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host–pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation,

Aridaman Pandit; Somdatta Sinha

2011-01-01

182

Evidence of selectively driven codon usage in rice: Implications for GC content evolution of Gramineae genes  

Microsoft Academic Search

Two gene classes characterized by high and low GC content have been found in rice and other cereals, but not dicot genomes. We used paralogs with high and low GC contents in rice and found: (a) a greater increase in GC content at exonic fourfold-redundant sites than at flanking introns; (b) with reference to their orthologs in Arabidopsis, most substitution

Xingyi Guo; Jiandong Bao; Longjiang Fan

2007-01-01

183

GC COMPOSITION AND CODON USAGE IN GENES OF INBREEDING AND OUTCROSSING TRITICEAE SPECIES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Wheat chromosomes are characterized by a steep gradient of recombination rate along chromosome arms. The mating system of Triticeae species varies from outcrossing to almost complete selfing. A relevant question is how these two important factors affect the gene composition. Wheat contigs were ana...

184

A CUG codon adapted two-hybrid system for the pathogenic fungus Candida albicans  

PubMed Central

The genetics of the most common human pathogenic fungus Candida albicans has several unique characteristics. Most notably, C. albicans does not follow the universal genetic code, by translating the CUG codon into serine instead of leucine. Consequently, the use of Saccharomyces cerevisiae as a host for yeast two-hybrid experiments with C. albicans proteins is limited due to erroneous translation caused by the aberrant codon usage of C. albicans. To circumvent the need for heterologous expression and codon optimalization of C. albicans genes we constructed a two-hybrid system with C. albicans itself as the host with components that are compatible for use in this organism. The functionality of this two-hybrid system was shown by successful interaction assays with the protein pairs Kis1–Snf4 and Ino4-Ino2. We further confirmed interactions between components of the filamentation/mating MAP kinase pathway, including the unsuspected interaction between the MAP kinases Cek2 and Cek1. We conclude that this system can be used to enhance our knowledge of protein–protein interactions in C. albicans.

Stynen, Bram; Van Dijck, Patrick; Tournu, Helene

2010-01-01

185

Upstream start codon in segment 4 of North American H2 avian influenza A viruses.  

PubMed

H2N2 influenza A virus was the cause of the 1957 pandemic. Due to its constant presence in birds, the H2 subtype remains a topic of interest. In this work, comparison of H2 leader sequences of influenza A segment 4 revealed the presence of an upstream in-frame start codon in a majority of North American avian strains. This AUG is located seven codons upstream of the conventional start codon and is in a good Kozak context. In vivo experiments, using a luciferase reporter gene fused to leader sequences derived from North American avian H2 strains, support the efficient use of the upstream start codon. These results were corroborated by in vitro translation data using full-length segment 4 mRNA. Phylogenic analyses indicate that the upstream AUG, first detected in 1976, is stably nested in the North American avian lineage of H2 strains nowadays. The possible consequences of the upstream AUG are discussed. PMID:21232632

Girard, Geneviève; Gultyaev, Alexander P; Olsthoorn, René C L

2011-01-11

186

Determinants of supplement usage  

Microsoft Academic Search

Background: As the use of supplements is growing, this study examines the determinants of vitamin and herbal supplement usage. Instead of treating these as all-encompassing categories, they are broken into specific vitamins and herbs and compared to see if users are different. A measure of frequency of vitamin use is also created.Methods: Logistic and ordinal logistic regressions are run on

Dana Fennell

2004-01-01

187

Role for gene sequence, codon bias and mRNA folding energy in modulating structural symmetry of proteins.  

PubMed

Structural symmetry in proteins is commonly observed in the majority of fundamental protein folds. Meanwhile, nascent polypeptide chains of proteins have the potential to start the co-translational folding process and this process can have drastic effects on protein structure. Thus we are interested in understanding mechanisms that gene adopts in specifying structural symmetry in proteins. In the present paper, we reveal that for two representative symmetric proteins from (a?)8-barrel fold and beta-trefoil fold, intragenic symmetry is detected in the corresponding gene sequences. Codon bias and mRNA folding energy might be involved in mediating translation speed for the formation of structural symmetry: at least one major decrease in both codon bias and mRNA folding energy can be observed in the connecting region of the symmetric substructures along the codon sequence. Results suggest that gene duplication and fusion is responsible for structural symmetry in these proteins, and the usage of rare codons or higher order of secondary structure near the boundaries of symmetric substructures might be selected in order to slow down translation speed for effectively co-translational folding process of symmetric proteins. PMID:24109757

Shen, Xiaojuan; Chen, Shixiong; Li, Guanglin

2013-07-01

188

Two-codon T-box riboswitch binding two tRNAs.  

PubMed

T-box riboswitches control transcription of downstream genes through the tRNA-binding formation of terminator or antiterminator structures. Previously reported T-boxes were described as single-specificity riboswitches that can bind specific tRNA anticodons through codon-anticodon interactions with the nucleotide triplet of their specifier loop (SL). However, the possibility that T-boxes might exhibit specificity beyond a single tRNA had been overlooked. In Clostridium acetobutylicum, the T-box that regulates the operon for the essential tRNA-dependent transamidation pathway harbors a SL with two potential overlapping codon positions for tRNA(Asn) and tRNA(Glu). To test its specificity, we performed extensive mutagenic, biochemical, and chemical probing analyses. Surprisingly, both tRNAs can efficiently bind the SL in vitro and in vivo. The dual specificity of the T-box is allowed by a single base shift on the SL from one overlapping codon to the next. This feature allows the riboswitch to sense two tRNAs and balance the biosynthesis of two amino acids. Detailed genomic comparisons support our observations and suggest that "flexible" T-box riboswitches are widespread among bacteria, and, moreover, their specificity is dictated by the metabolic interconnection of the pathways under control. Taken together, our results support the notion of a genome-dependent codon ambiguity of the SLs. Furthermore, the existence of two overlapping codons imposes a unique example of tRNA-dependent regulation at the transcriptional level. PMID:23858450

Saad, Nizar Y; Stamatopoulou, Vassiliki; Brayé, Mélanie; Drainas, Denis; Stathopoulos, Constantinos; Becker, Hubert Dominique

2013-07-15

189

Certification of Memory Usage  

Microsoft Academic Search

\\u000a We describe a type-based approach for inferring heap space usage of certain functional programs and a mechanism for generating\\u000a certificates as to the thus inferred memory consumption in the form of proofs in a VDM-style program logic fore Java bytecode\\u000a (Java bytecode being the target of compilation). This gives a current snapshot of our work in the EU-funded project ‘Mobile

Martin Hofmann

2003-01-01

190

Putative mitochondrial polypeptides coded by expanded quadruplet codons, decoded by antisense tRNAs with unusual anticodons.  

PubMed

Weak triplet codon-anticodon interactions render ribosome-free translation unlikely. Some modern tRNAs read quadruplet codons (tetracodons), suggesting vestigial ribosome-free translation. Here, mitochondrial genomes are explored for tetracoded overlapping protein coding (tetra)genes. Occasional single tetracodons within regular mitochondrial genes coevolve positively/negatively with antisense tRNAs with predicted reduced/expanded anticodons (depending on taxon), suggesting complex tetra-decoding mechanisms. Transcripts of antisense tRNAs with unusual anticodons are more abundant than of homologues with regular anticodons. Assuming overlapping tetracoding with silent 4th tetracodon position, BLAST aligns 10 putative tetragenes spanning 17% of regular human mitochondrial protein coding tricodons with 14 GenBank proteins. Various tests including predicted peptide secondary structures, 3rd codon position (of the regular main frame of the protein coding gene) conservation against replicational deamination mutation gradients, and circular code usage (overlapping genes avoid using circular code codons) confirm tetracoding in these overlapping tetragenes with silent 4th position, but not for BLAST-predicted tetragenes assuming silent 2nd or 3rd positions. This converges with tetradecoding mechanisms that are more compatible with silent 4th, than at other, tetracodon positions. Tetracoding increases with (a) GC-contents, perhaps conserved or switched on in high temperature conditions; (b) usage of theoretically predicted 'tessera' tetracodons; (c) 12s rRNA stability; and d) antisense tRNA numbers with predicted expanded anticodons. Most detected tetragenes are not evolutionarily conserved, apparently reflect specific, transient adaptations. Tetracoding increases with mammal longevity. PMID:23041464

Seligmann, Hervé

2012-10-04

191

Nonrandom intragenic variations in patterns of codon bias implicate a sequential interplay between transitional genetic drift and functional amino acid selection.  

PubMed

Although most codon third bases appear to be functionless, the synonymous codons so defined exhibit a strikingly nonrandom distribution (codon bias) within human and other genes. To examine this phenomenon further, we generated a database of DNA sequences encoding human transmembrane cell-surface receptor proteins. Using this database we show here that the guanine and cytosine content of codon third bases (GC3) varies intragenically with the nature of the specified receptor domains (transmembrane > extracellular > intracellular domains; p < 0.001), the phenotype of the encoded amino acids (hydrophobic > hydrophilic > neutral amino acids; p < 0.001), and the receptor affiliation of the transmembrane (G-protein-coupled receptors > receptor tyrosine kinases; p < 0.001). Within gene regions specifying transmembrane domains, GC3 declines as domain functionality becomes redundant with increasing hydrophobicity (p < 0.001). Codons containing the second-base cytosine (XCZ, which encodes neutral amino acids) are selectively depleted of third-base adenine content (A3: XCA codons) when encoding transmembrane domain residues, consistent with positive selection for transitional mutation of XCG to XTG (which encodes hydrophobic amino acids) rather than to the synonymous XCA. Supporting this XCG --> XTG mechanism of codon bias, the G3:A3 ratio of codons specifying the transmembrane amino acid glycine (GGZ) is intermediate between that of its functional homolog alanine (GCZ) and that of hydrophobic valine (GTZ), even though the C3:T3 ratios are similar. Conversely, nearest-neighbor analysis of third bases 5' to codons specifying valine and leucine (CTZ) confirms a significant difference in C3:T3 but not G3:A3 ratios (i.e., C3/G1 --> T3/G1 > C3/A1; p < 0.001), consistent with the functionally advantageous retention of hydrophobic residues. These data raise the possibility that patterns of intragenic codon bias reflect a balance between negative and positive selection, suggesting in turn that analysis of codon third-base usage may help to predict the functional significance of encoded products. PMID:14738312

Lin, K; Tan, S B; Kolatkar, P R; Epstein, R J

2003-11-01

192

Selection of an avian retrovirus mutant with extended receptor usage.  

PubMed Central

Receptor recognition by avian retroviruses is thought to involve the interaction of two regions of the SU protein, hr1 and hr2, with the host cell surface receptor. These regions exhibit considerable variation, concordant with differences in receptor usage among the many avian leukosis virus subgroups. We hypothesize that some retroviruses have altered receptor usage in response to selective pressures imposed by receptor polymorphisms in their hosts. To test this hypothesis, we passaged td-Pr-RSV-B on cocultured permissive chicken (C/E) and nonpermissive quail (QT6/BD) cells. A variant virus with an expanded host range was identified at passage 29 and ultimately shown to be identical in sequence to td-Pr-RSV-B, except for changes at codons 155 and 156 of SU amino acid corresponding to two amino acid changes within hr1. Superinfection resistance studies suggest that the variant virus recognizes the subgroup B receptor on chicken cells and the subgroup E receptor on quail cells. These findings indicate that altered receptor usage can be conferred by small changes in env and may point to a key region for receptor interaction. Further, they demonstrate the evolutionary potential of retroviral env genes to alter receptor usage in response to appropriate selective pressure.

Taplitz, R A; Coffin, J M

1997-01-01

193

UAG is a sense codon in several chlorophycean mitochondria.  

PubMed

The mitochondrial genetic code of those land plants and green algae that have been examined does not deviate from the universal one. A red alga, Chondrus crispus, is the sole reported example throughout the algae that uses a deviant (non-universal) mitochondrial genetic code (UGA=Trp). We have analyzed 366-bp DNA sequences of the gene for mitochondrial cytochrome oxidase subunit I (COXI) from ten chlorophyceaen algae, and detected 3-8 in-frame UAG codons in the sequences of five species. Comparisons of these sequences with those of other algae and land plants have shown that most of the UAG sites in Hydrodictyon reticulatum, Pediastrum boryanum and Tetraedron bitridens correspond to alanine, and those of Coelastrum microporum and Scenedesmus quadricauda to leucine. The three species in which UAG probably codes for alanine are characterized by zoospore formation in asexual reproduction and form a clade in the COXI phylogenetic tree. The two species in which UAG codes for leucine are known to form daughter coenobia and pair in the tree. This is the first report on a deviant mitochondrial genetic code in green algae. Mutational change(s) in the release factor corresponding to UAG would be involved in these code changes. No genetic code deviation has been found in five other species examined. PMID:8662206

Hayashi-Ishimaru, Y; Ohama, T; Kawatsu, Y; Nakamura, K; Osawa, S

1996-06-01

194

Slow fitness recovery in a codon-modified viral genome.  

PubMed

Extensive synonymous codon modification of viral genomes appears to be an effective way of attenuating strains for use as live vaccines. An assumption of this method is that codon changes have individually small effects, such that codon-attenuated viruses will be slow to evolve back to high fitness (and thus to high virulence). The major capsid gene of the bacterial virus T7 was modified to have varying levels of suboptimal synonymous codons in different constructs, and fitnesses declined linearly with the number of changes. Adaptation of the most extreme design, with 182 codon changes, resulted in a slow fitness recovery by standards of previous experimental evolution with this virus, although fitness effects of substitutions were higher than expected from the average effect of an engineered codon modification. Molecular evolution during recovery was modest, and changes evolved both within the modified gene and outside it. Some changes within the modified gene evolved in parallel across replicates, but with no obvious explanation. Overall, the study supports the premise that codon-modified viruses recover fitness slowly, although the evolution is substantially more rapid than expected from the design principle. PMID:22532576

Bull, J J; Molineux, I J; Wilke, C O

2012-04-24

195

Genetic immunization with codon-optimized equine infectious anemia virus (EIAV) surface unit (SU) envelope protein gene sequences stimulates immune responses in ponies  

Microsoft Academic Search

In the context of DNA vaccines the native equine infectious anemia virus (EIAV)-envelope gene has proven to be an extremely weak immunogen in horses probably because the RNA transcripts are poorly expressed owing to an unusual codon-usage bias, the possession of multiple RNA splice sites and potential adenosine-rich RNA instability elements. To overcome these problems a synthetic version of sequences

R. Frank Cook; Sheila J. Cook; Pamela S. Bolin; Laryssa J. Howe; Weisong Zhou; Ronald C. Montelaro; Charles J. Issel

2005-01-01

196

Online CME usage patterns.  

PubMed

The paper reports the findings of the analysis of a sample of 829 online Continuous Medical Education (CME) enrolments aimed at inspecting users' preferences and behaviours. The contents of the analyzed course are provided as online SCORM (Sharable Content Object Reference Model) resources together with the corresponding Pdf downloadable versions allowing different usage patterns (online only, Pdf only, online AND Pdf, mixed online OR Pdf). The results point out that there is not a specific preference for one of the four patterns and that most of the users access both navigable modules and Pdf documents. Demographic characteristics and initial knowledge level do not influence the choice of a specific usage pattern that probably depends on internal or context factors. From the point of view of knowledge acquisition, the four patterns are equivalent. As regards users' behaviour, the analysis has pointed out two issues: 1) the attitude to conclude the course in a short time and to reach good test scores, but not the excellence; 2) learning activity tracing data were not available for all the enrolments. Cues for discussion are proposed. PMID:21893749

Mazzoleni, M Cristina; Rognoni, Carla; Finozzi, Enrico; Giorgi, Ines; Pagani, Marco; Imbriani, Marcello

2011-01-01

197

20. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, ARCH DETAIL ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, ARCH DETAIL SHOWING BRICK ARCH FOR MAIN SPAN AND STONE VOUSSOIRS. VIEW W. - Gettysburg National Military Park Tour Roads, Gettysburg, Adams County, PA

198

Tracing Specific Synonymous Codon–Secondary Structure Correlations Through Evolution  

Microsoft Academic Search

  Abstract\\u000a \\u000a We previously showed that GAU codons are preferred (relative to synonymous GAC codons) for encoding aspartates specifically\\u000a at the N-termini of ?-helices in human, but not in E. coli, proteins. To test if this difference reflected a general difference between eucaryotes and procaryotes, we now extended\\u000a the analysis to include the proteins and coding sequences of mammals, vertebrates, S.

Matej Oreši?; Michael H. H. Dehn; Daniel H. H. Korenblum; David H. H. Shalloway

2003-01-01

199

An evaluation of data-driven motion estimation in comparison to the usage of external-surrogates in cardiac SPECT imaging.  

PubMed

Motion estimation methods in single photon emission computed tomography (SPECT) can be classified into methods which depend on just the emission data (data-driven), or those that use some other source of information such as an external surrogate. The surrogate-based methods estimate the motion exhibited externally which may not correlate exactly with the movement of organs inside the body. The accuracy of data-driven strategies on the other hand is affected by the type and timing of motion occurrence during acquisition, the source distribution, and various degrading factors such as attenuation, scatter, and system spatial resolution. The goal of this paper is to investigate the performance of two data-driven motion estimation schemes based on the rigid-body registration of projections of motion-transformed source distributions to the acquired projection data for cardiac SPECT studies. Comparison is also made of six intensity based registration metrics to an external surrogate-based method. In the data-driven schemes, a partially reconstructed heart is used as the initial source distribution. The partially-reconstructed heart has inaccuracies due to limited angle artifacts resulting from using only a part of the SPECT projections acquired while the patient maintained the same pose. The performance of different cost functions in quantifying consistency with the SPECT projection data in the data-driven schemes was compared for clinically realistic patient motion occurring as discrete pose changes, one or two times during acquisition. The six intensity-based metrics studied were mean-squared difference, mutual information, normalized mutual information (NMI), pattern intensity (PI), normalized cross-correlation and entropy of the difference. Quantitative and qualitative analysis of the performance is reported using Monte-Carlo simulations of a realistic heart phantom including degradation factors such as attenuation, scatter and system spatial resolution. Further the visual appearance of motion-corrected images using data-driven motion estimates was compared to that obtained using the external motion-tracking system in patient studies. Pattern intensity and normalized mutual information cost functions were observed to have the best performance in terms of lowest average position error and stability with degradation of image quality of the partial reconstruction in simulations. In all patients, the visual quality of PI-based estimation was either significantly better or comparable to NMI-based estimation. Best visual quality was obtained with PI-based estimation in one of the five patient studies, and with external-surrogate based correction in three out of five patients. In the remaining patient study there was little motion and all methods yielded similar visual image quality. PMID:24107647

Mukherjee, Joyeeta Mitra; Hutton, Brian F; Johnson, Karen L; Pretorius, P Hendrik; King, Michael A

2013-10-10

200

An evaluation of data-driven motion estimation in comparison to the usage of external-surrogates in cardiac SPECT imaging  

NASA Astrophysics Data System (ADS)

Motion estimation methods in single photon emission computed tomography (SPECT) can be classified into methods which depend on just the emission data (data-driven), or those that use some other source of information such as an external surrogate. The surrogate-based methods estimate the motion exhibited externally which may not correlate exactly with the movement of organs inside the body. The accuracy of data-driven strategies on the other hand is affected by the type and timing of motion occurrence during acquisition, the source distribution, and various degrading factors such as attenuation, scatter, and system spatial resolution. The goal of this paper is to investigate the performance of two data-driven motion estimation schemes based on the rigid-body registration of projections of motion-transformed source distributions to the acquired projection data for cardiac SPECT studies. Comparison is also made of six intensity based registration metrics to an external surrogate-based method. In the data-driven schemes, a partially reconstructed heart is used as the initial source distribution. The partially-reconstructed heart has inaccuracies due to limited angle artifacts resulting from using only a part of the SPECT projections acquired while the patient maintained the same pose. The performance of different cost functions in quantifying consistency with the SPECT projection data in the data-driven schemes was compared for clinically realistic patient motion occurring as discrete pose changes, one or two times during acquisition. The six intensity-based metrics studied were mean-squared difference, mutual information, normalized mutual information (NMI), pattern intensity (PI), normalized cross-correlation and entropy of the difference. Quantitative and qualitative analysis of the performance is reported using Monte-Carlo simulations of a realistic heart phantom including degradation factors such as attenuation, scatter and system spatial resolution. Further the visual appearance of motion-corrected images using data-driven motion estimates was compared to that obtained using the external motion-tracking system in patient studies. Pattern intensity and normalized mutual information cost functions were observed to have the best performance in terms of lowest average position error and stability with degradation of image quality of the partial reconstruction in simulations. In all patients, the visual quality of PI-based estimation was either significantly better or comparable to NMI-based estimation. Best visual quality was obtained with PI-based estimation in one of the five patient studies, and with external-surrogate based correction in three out of five patients. In the remaining patient study there was little motion and all methods yielded similar visual image quality.

Mitra Mukherjee, Joyeeta; Hutton, Brian F.; Johnson, Karen L.; Hendrik Pretorius, P.; King, Michael A.

2013-11-01

201

Mutations at codons 178, 200-129, and 232 contributed to the inherited prion diseases in Korean patients  

PubMed Central

Background Polymorphisms of the human prion protein gene (PRNP) contribute to the genetic determinants of Creutzfeldt-Jakob disease (CJD). Numerous polymorphisms in the promoter regions as well as the open reading frame of PRNP were investigated. Greater than 90% of Korean, Chinese, and Japanese carry the homozygote 129 MM codon. In Korea, polymorphisms have not been comprehensively studied, except codons 129 and 219 in PRNP among Korean CJD cases. Although polymorphisms at codons 129 and 219 play an important role in susceptibility to sporadic CJD, patients with other polymorphisms in PRNP exhibited critical distinctions of clinical symptoms. Methods The genetic analyses of PRNP were carried out among probable CJD patients in comparison with the results from magnetic resonance imaging (MRI) and electroencephalogram (EEG). Results The molecular analyses revealed that three mutations at codons D178N, E200K, and M232R in heterozygosity. Patients with the D178N and M232R mutations had a 129MM codon, whereas the patient with the E200K mutation showed 129MV heterozygosity. They all revealed strong 14-3-3 positive signals. The 67-year-old patient with the D178N-129M mutation showed progressive gait disturbance and dysarthria was in progress. The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms. The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms. Conclusion Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.

2009-01-01

202

Usage Management in Cloud Computing  

Microsoft Academic Search

User concerns regarding data handling within the cloud will gain increasing importance as cloud computing becomes more pervasive. Existing service level agreement (SLA) frameworks are not designed for flexibly handling even relatively straightforward usage policies. This paper introduces the notion and importance of usage management in cloud computing. It provides an analysis of features and challenges involved in deploying a

Pramod A. Jamkhedkar; Christopher C. Lamb; Gregory L. Heileman

2011-01-01

203

Media Portal of Alcohol Usage  

Microsoft Academic Search

Alcohol abuse remains a continuing problem throughout many cultures. Researchers have suggested that a contributing factor to alcohol abuse may be the ways in which the media portray alcohol usage in television programming. This study investigates the ways in which Korean television programming portrays alcohol usage and the potential linkages to alcohol abuse in that country.

Hae-Young Bang; Peter M. Sanchez

2003-01-01

204

Codon Preference Optimization Increases Prokaryotic Cystatin C Expression  

PubMed Central

Gene expression is closely related to optimal vector-host system pairing in many prokaryotes. Redesign of the human cystatin C (cysC) gene using the preferred codons of the prokaryotic system may significantly increase cysC expression in Escherichia coli (E. coli). Specifically, cysC expression may be increased by removing unstable sequences and optimizing GC content. According to E. coli expression system codon preferences, the gene sequence was optimized while the amino acid sequence was maintained. The codon-optimized cysC (co-cysC) and wild-type cysC (wt-cysC) were expressed by cloning the genes into a pET-30a plasmid, thus transforming the recombinant plasmid into E. coli BL21. Before and after the optimization process, the prokaryotic expression vector and host bacteria were examined for protein expression and biological activation of CysC. The recombinant proteins in the lysate of the transformed bacteria were purified using Ni2+-NTA resin. Recombinant protein expression increased from 10% to 46% based on total protein expression after codon optimization. Recombinant CysC purity was above 95%. The significant increase in cysC expression in E. coli expression produced by codon optimization techniques may be applicable to commercial production systems.

Wang, Qing; Mei, Cui; Zhen, Honghua; Zhu, Jess

2012-01-01

205

Identification of stop codon readthrough genes in Saccharomyces cerevisiae  

PubMed Central

We specifically sought genes within the yeast genome controlled by a non-conventional translation mechanism involving the stop codon. For this reason, we designed a computer program using the yeast database genomic regions, and seeking two adjacent open reading frames separated only by a unique stop codon (called SORFs). Among the 58 SORFs identified, eight displayed a stop codon bypass level ranging from 3 to 25%. For each of the eight sequences, we demonstrated the presence of a poly(A) mRNA. Using isogenic [PSI+] and [psi–] yeast strains, we showed that for two of the sequences the mechanism used is a bona fide readthrough. However, the six remaining sequences were not sensitive to the PSI state, indicating either a translation termination process independent of eRF3 or a new stop codon bypass mechanism. Our results demonstrate that the presence of a stop codon in a large ORF may not always correspond to a sequencing error, or a pseudogene, but can be a recoding signal in a functional gene. This emphasizes that genome annotation should take into account the fact that recoding signals could be more frequently used than previously expected.

Namy, Olivier; Duchateau-Nguyen, Guillemette; Hatin, Isabelle; Hermann-Le Denmat, Sylvie; Termier, Michel; Rousset, Jean-Pierre

2003-01-01

206

Dual functions of codons in the genetic code  

PubMed Central

The discovery of the genetic code provided one of the basic foundations of modern molecular biology. Most organisms use the same genetic language, but there are also well-documented variations representing codon reassignments within specific groups of organisms (such as ciliates and yeast) or organelles (such as plastids and mitochondria). In addition, duality in codon function is known in the use of AUG in translation initiation and methionine insertion into internal protein positions as well as in the case of selenocysteine and pyrrolysine insertion (encoded by UGA and UAG, respectively) in competition with translation termination. Ambiguous meaning of CUG in coding for serine and leucine is also known. However, a recent study revealed that codons in any position within the open reading frame can serve a dual function and that a change in codon meaning can be achieved by availability of a specific type of RNA stem-loop structure in the 3’-untranslated region. Thus, duality of codon function is a more widely used feature of the genetic code than previously known, and this observation raises the possibility that additional recoding events and additional novel features have evolved in the genetic code.

Lobanov, Alexey V.; Turanov, Anton A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

207

An expanded genetic code with a functional quadruplet codon  

PubMed Central

With few exceptions the genetic codes of all known organisms encode the same 20 amino acids, yet all that is required to add a new building block are a unique tRNA/aminoacyl-tRNA synthetase pair, a source of the amino acid, and a unique codon that specifies the amino acid. For example, the amber nonsense codon, TAG, together with orthogonal Methanococcus jannaschii or Escherichia coli tRNA/synthetase pairs have been used to genetically encode a variety of unnatural amino acids in E. coli and yeast, respectively. However, the availability of noncoding triplet codons ultimately limits the number of amino acids encoded by any organism. Here, we report the design and generation of an orthogonal synthetase/tRNA pair derived from archaeal tRNALys sequences that efficiently and selectively incorporates an unnatural amino acid into proteins in response to the quadruplet codon, AGGA. Frameshift suppression with l-homoglutamine (hGln) does not significantly affect protein yields or cell growth rates and is mutually orthogonal with amber suppression, permitting the simultaneous incorporation of two unnatural amino acids, hGln and O-methyl-l-tyrosine, at distinct positions within myoglobin. This work suggests that neither the number of available triplet codons nor the translational machinery itself represents a significant barrier to further expansion of the genetic code.

Anderson, J. Christopher; Wu, Ning; Santoro, Stephen W.; Lakshman, Vishva; King, David S.; Schultz, Peter G.

2004-01-01

208

The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in Northern Greece  

Microsoft Academic Search

The aim of this study was to explore a possible association between p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms and breast cancer in Northern Greece. We examined 42 women with breast cancer and 51 controls. A total of 42 women with breast cancer as well as healthy controls were investigated and results showed that p53 codon

Theodora G. Kalemi; Alexandros F. Lambropoulos; Maria Gueorguiev; Sofia Chrisafi; Konstantinos T. Papazisis; Alexandros Kotsis

2005-01-01

209

Comparison of the effects of 2,3-butanedione monoxime on force production, myosin light chain phosphorylation and chemical energy usage in intact and permeabilized smooth and skeletal muscles  

Microsoft Academic Search

The primary goal of this study was to determine the utility of 2,3-butanedione monoxime as a tool for determining and separating the chemical energy usage associated with force production from that of force-independent, or ‘activation’ processes in smooth and skeletal muscles. We determined the effects of 2,3-butanedione monoxime on force production, myosin light chain phosphorylation and high energy phosphate usage

Marion J. Siegman; Susan U. Mooers; Thomas B. Warren; David M. Warshaw; Mitsuo Ikebe; Thomas M. Butler

1994-01-01

210

Gene Expression, Amino Acid Conservation, and Hydrophobicity Are the Main Factors Shaping Codon Preferences in Mycobacterium tuberculosis and Mycobacterium leprae  

Microsoft Academic Search

.  \\u000a \\u000a Mycobacterium tuberculosis and Mycobacterium leprae are the ethiological agents of tuberculosis and leprosy, respectively. After performing extensive comparisons between genes\\u000a from these two GC-rich bacterial species, we were able to construct a set of 275 homologous genes. Since these two bacterial\\u000a species also have a very low growth rate, translational selection could not be so determinant in their codon

Antonio B. de Miranda; Fernando Alvarez-Valin; Kamel Jabbari; Wim M. Degrave; Giorgio Bernardi

2000-01-01

211

Model for Codon Position Bias in RNA Editing  

NASA Astrophysics Data System (ADS)

RNA editing can be crucial for the expression of genetic information via inserting, deleting, or substituting a few nucleotides at specific positions in an RNA sequence. Within coding regions in an RNA sequence, editing usually occurs with a certain bias in choosing the positions of the editing sites. In the mitochondrial genes of Physarum polycephalum, many more editing events have been observed at the third codon position than at the first and second, while in some plant mitochondria the second codon position dominates. Here we propose an evolutionary model that explains this bias as the basis of selection at the protein level. The model predicts a distribution of the three positions rather close to the experimental observation in Physarum. This suggests that the codon position bias in Physarum is mainly a consequence of selection at the protein level.

Liu, Tsunglin; Bundschuh, Ralf

2005-08-01

212

A model for codon position bias in RNA editing  

NASA Astrophysics Data System (ADS)

RNA editing can be crucial for the expression of genetic information via inserting, deleting, or substituting a few nucleotides at specific positions in an RNA sequence. Within coding regions in an RNA sequence, editing usually occurs with a certain bias in choosing the positions of the editing sites. In the mitochondrial genes of Physarum polycephalum, many more editing events have been observed at the third codon position than at the first and second, while in some plant mitochondria the second codon position dominates. Here we propose an evolutionary model that explains this bias as the basis of selection at the protein level. The model predicts a distribution of the three positions rather close to the experimental observation in Physarum. This suggests that the codon position bias in Physarum is mainly a consequence of selection at the protein level.

Bundschuh, Ralf; Liu, Tsunglin

2006-03-01

213

Codon reassignment in the Escherichia coli genetic code  

PubMed Central

Most organisms, from Escherichia coli to humans, use the ‘universal’ genetic code, which have been unchanged or ‘frozen’ for billions of years. It has been argued that codon reassignment causes mistranslation of genetic information, and must be lethal. In this study, we successfully reassigned the UAG triplet from a stop to a sense codon in the E. coli genome, by eliminating the UAG-recognizing release factor, an essential cellular component, from the bacterium. Only a few genetic modifications of E. coli were needed to circumvent the lethality of codon reassignment; erasing all UAG triplets from the genome was unnecessary. Thus, UAG was assigned unambiguously to a natural or non-natural amino acid, according to the specificity of the UAG-decoding tRNA. The result reveals the unexpected flexibility of the genetic code.

Mukai, Takahito; Hayashi, Akiko; Iraha, Fumie; Sato, Aya; Ohtake, Kazumasa; Yokoyama, Shigeyuki; Sakamoto, Kensaku

2010-01-01

214

Reduction of the Rate of Poliovirus Protein Synthesis through Large-Scale Codon Deoptimization Causes Attenuation of Viral Virulence by Lowering Specific Infectivity  

PubMed Central

Exploring the utility of de novo gene synthesis with the aim of designing stably attenuated polioviruses (PV), we followed two strategies to construct PV variants containing synthetic replacements of the capsid coding sequences either by deoptimizing synonymous codon usage (PV-AB) or by maximizing synonymous codon position changes of the existing wild-type (wt) poliovirus codons (PV-SD). Despite 934 nucleotide changes in the capsid coding region, PV-SD RNA produced virus with wild-type characteristics. In contrast, no viable virus was recovered from PV-AB RNA carrying 680 silent mutations, due to a reduction of genome translation and replication below a critical level. After subcloning of smaller portions of the AB capsid coding sequence into the wt background, several viable viruses were obtained with a wide range of phenotypes corresponding to their efficiency of directing genome translation. Surprisingly, when inoculated with equal infectious doses (PFU), even the most replication-deficient viruses appeared to be as pathogenic in PV-sensitive CD155tg (transgenic) mice as the PV(M) wild type. However, infection with equal amounts of virus particles revealed a neuroattenuated phenotype over 100-fold. Direct analysis indicated a striking reduction of the specific infectivity of PV-AB-type virus particles. Due to the distribution effect of many silent mutations over large genome segments, codon-deoptimized viruses should have genetically stable phenotypes, and they may prove suitable as attenuated substrates for the production of poliovirus vaccines.

Mueller, Steffen; Papamichail, Dimitris; Coleman, J. Robert; Skiena, Steven; Wimmer, Eckard

2006-01-01

215

Marijuana Usage and Hypnotic Susceptibility  

ERIC Educational Resources Information Center

Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

Franzini, Louis R.; McDonald, Roy D.

1973-01-01

216

The 'polysemous' codon--a codon with multiple amino acid assignment caused by dual specificity of tRNA identity.  

PubMed Central

In some Candida species, the universal CUG leucine codon is translated as serine. However, in most cases, the serine tRNAs responsible for this non-universal decoding (tRNA(Ser)CAG) accept in vitro not only serine, but also, to some extent, leucine. Nucleotide replacement experiments indicated that m1G37 is critical for leucylation activity. This finding was supported by the fact that the tRNA(Ser)CAGs possessing the leucylation activity always have m1G37, whereas that of Candida cylindracea, which possesses no leucylation activity, has A37. Quantification of defined aminoacetylated tRNAs in cells demonstrated that 3% of the tRNA(Ser)CAGs possessing m1G37 were, in fact, charged with leucine in vivo. A genetic approach using an auxotroph mutant of C.maltosa possessing this type of tRNA(Ser)CAG also suggested that the URA3 gene inactivated due to the translation of CUG as serine was rescued by a slight incorporation of leucine into the polypeptide, which demonstrated that the tRNA charged with multiple amino acids could participate in the translation. These findings provide the first evidence that two distinct amino acids are assigned by a single codon, which occurs naturally in the translation process of certain Candida species. We term this novel type of codon a 'polysemous codon'.

Suzuki, T; Ueda, T; Watanabe, K

1997-01-01

217

A new ?-thalassemia deletion mutation [codon 36 (-C)] observed in a Chinese woman.  

PubMed

In this study we present the first report of the detection of a new ?-thalassemia (?-thal) mutation at codon 36 (-C) in the Chinese population. This frameshift mutation generates a TGA stop codon at position 60, resulting in a thalassemia phenotype. This is the first example of a premature stop codon at position 60 because of codon 36. The characterization of uncommon mutations is useful for the screening of ?-thal carriers, genetic counseling and prenatal diagnosis. PMID:21077770

Huang, Hailong; Xu, Liangpu; Lin, Na; Xu, Jinbang; He, Deqin; Li, Ying; Zheng, Lin; Liu, Hekun; Lin, Yuan

2010-01-01

218

A Model of Proto-Anti-Codon RNA Enzymes Requiring l Amino Acid Homochirality  

Microsoft Academic Search

All living organisms encode the 20 natural amino acid units of polypeptides using a universal scheme of triplet nucleotide\\u000a “codons”. Disparate features of this codon scheme are potentially informative of early molecular evolution: (i) the absence\\u000a of any codons for d-amino acids; (ii) the odd combination of alternate codon patterns for some amino acids; (iii) the confinement of synonymous\\u000a positions

Albert Erives

219

Internal editing of the maize chloroplast ndhA transcript restores codons for conserved amino acids.  

PubMed Central

The NADH dehydrogenase subunit A (ndhA) gene from maize chloroplasts encodes a highly conserved peptide, which at several positions could be restored to consensus sequences by potential C-to-U editing of the codons involved. This gene was, therefore, chosen for analysis of its mRNA sequence in the form of amplified cDNA. A comparison of this cDNA sequence with the plastome-encoded ndhA sequence reveals four C-to-U editing sites, thereby demonstrating as a novel finding that chloroplast editing can also affect internal mRNA positions. All the edited codons restore amino acids that are conserved in the ndhA-encoded peptides of other chloroplast species. Alignment with homologous mitochondrial NADH-ubiquinone reductase subunit 1 (nad1) sequences of plant and even nonplant species shows that two of the editing positions restore universally conserved amino acids and that one editing site is even shared with nad1 mRNA of plant mitochondria. No editing sites could be detected in the cDNA derived from transcripts of the maize chloroplast RNA polymerase alpha-subunit (rpoA) gene.

Maier, R M; Hoch, B; Zeltz, P; Kossel, H

1992-01-01

220

Resolving Discrepancy between Nucleotides and Amino Acids in Deep-Level Arthropod Phylogenomics: Differentiating Serine Codons in 21-Amino-Acid Models  

PubMed Central

Background In a previous study of higher-level arthropod phylogeny, analyses of nucleotide sequences from 62 protein-coding nuclear genes for 80 panarthopod species yielded significantly higher bootstrap support for selected nodes than did amino acids. This study investigates the cause of that discrepancy. Methodology/Principal Findings The hypothesis is tested that failure to distinguish the serine residues encoded by two disjunct clusters of codons (TCN, AGY) in amino acid analyses leads to this discrepancy. In one test, the two clusters of serine codons (Ser1, Ser2) are conceptually translated as separate amino acids. Analysis of the resulting 21-amino-acid data matrix shows striking increases in bootstrap support, in some cases matching that in nucleotide analyses. In a second approach, nucleotide and 20-amino-acid data sets are artificially altered through targeted deletions, modifications, and replacements, revealing the pivotal contributions of distinct Ser1 and Ser2 codons. We confirm that previous methods of coding nonsynonymous nucleotide change are robust and computationally efficient by introducing two new degeneracy coding methods. We demonstrate for degeneracy coding that neither compositional heterogeneity at the level of nucleotides nor codon usage bias between Ser1 and Ser2 clusters of codons (or their separately coded amino acids) is a major source of non-phylogenetic signal. Conclusions The incongruity in support between amino-acid and nucleotide analyses of the forementioned arthropod data set is resolved by showing that “standard” 20-amino-acid analyses yield lower node support specifically when serine provides crucial signal. Separate coding of Ser1 and Ser2 residues yields support commensurate with that found by degenerated nucleotides, without introducing phylogenetic artifacts. While exclusion of all serine data leads to reduced support for serine-sensitive nodes, these nodes are still recovered in the ML topology, indicating that the enhanced signal from Ser1 and Ser2 is not qualitatively different from that of the other amino acids.

Zwick, Andreas; Regier, Jerome C.; Zwickl, Derrick J.

2012-01-01

221

Investigating protein-coding sequence evolution with probabilistic codon substitution models  

Microsoft Academic Search

Abstract This review is motivated by the true explosion in the number,of recent studies both developing and ameliorating probabilistic models of codon evolution. Traditionally parametric, the first codon models focused on estimating the effects of selective pressure on the protein via an explicit parameter in the maximum,likelihood framework. Likelihood ratio tests of nested codon models armed the biologists with powerful

Maria Anisimova; Carolin Kosiol

2008-01-01

222

Problem-Solving Test: The Effect of Synonymous Codons on Gene Expression  

ERIC Educational Resources Information Center

|Terms to be familiar with before you start to solve the test: the genetic code, codon, degenerate codons, protein synthesis, aminoacyl-tRNA, anticodon, antiparallel orientation, wobble, unambiguous codons, ribosomes, initiation, elongation and termination of translation, peptidyl transferase, translocation, degenerate oligonucleotides, green…

Szeberenyi, Jozsef

2009-01-01

223

Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid  

Microsoft Academic Search

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must

Lluís Aragonès; Susana Guix; Enric Ribes; Albert Bosch; Rosa M. Pintó

2010-01-01

224

HER-2 codon 655 polymorphism in cervical carcinogenesis.  

PubMed

HER-2 codon 655 polymorphism together with human papillomavirus (HPV) types were examined in a total of 279 cervical smear samples. Forty-nine patients with high-grade squamous intraepithelial lesion had higher frequency of high-risk HPV than 167 patients with low-grade squamous intraepithelial lesion and 63 controls. There was no statistical difference in the frequencies of HER-2 Ile/Ile, Ile/Val, and Val/Val genotypes between squamous intraepithelial lesions (SILs) and controls. When the Ile/Ile genotype was compared to the Ile/Val + Val/Val genotypes, there was also no statistical difference in the genotype prevalence between SILs and controls either in 91 or 188 patients with or without high-risk HPV, respectively. These results suggest that the HER-2 polymorphism at codon 655 in cervical cell samples is unlikely to be associated with HPV status and the onset of cervical cancer in a Japanese population. PMID:16445653

Ueda, M; Hung, Y-C; Terai, Y; Saito, J; Nunobiki, O; Noda, S; Ueki, M

225

Endosymbiotic origin and codon bias of the nuclear gene for chloroplast glyceraldehyde-3-phosphate dehydrogenase from maize.  

PubMed

The nuclei of plant cells harbor genes for two types of glyceraldehyde-3-phosphate dehydrogenases (GAPDH) displaying a sequence divergence corresponding to the prokaryote/eukaryote separation. This strongly supports the endosymbiotic theory of chloroplast evolution and in particular the gene transfer hypothesis suggesting that the gene for the chloroplast enzyme, initially located in the genome of the endosymbiotic chloroplast progenitor, was transferred during the course of evolution into the nuclear genome of the endosymbiotic host. Codon usage in the gene for chloroplast GAPDH of maize is radically different from that employed by present-day chloroplasts and from that of the cytosolic (glycolytic) enzyme from the same cell. This reveals the presence of subcellular selective pressures which appear to be involved in the optimization of gene expression in the economically important graminaceous monocots. PMID:3131533

Brinkmann, H; Martinez, P; Quigley, F; Martin, W; Cerff, R

1987-01-01

226

KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas  

Microsoft Academic Search

DNAs from human pancreatic adenocarcinomas were analyzed for the presence of mutations in codons 12, 13 and 61 of the NRAS, KRAS and HRAS gene. Formalin-fixed and paraffin-embedded tissue was used directly in an in vitro amplification reaction to expand the relevant RAS sequences. The mutations were detected by selective hybridization using mutation-specific synthetic oligonucleotides. In 28 of the 30

Vincent T. H. B. M. Smit; Angelina J. M. Boot; Alida M. M. Smits; Gert Jan Fleuren; Cees J. Cornelisse; Johannes L. Bos

1988-01-01

227

The influence of codon context on genetic code translation  

Microsoft Academic Search

A class of mutations that increase the efficiency of a suppressor tRNA in translating a particular amber codon has been characterized. The increased efficiency is due to a mutation resulting in a change in the mRNA that affects the nucleotide adjacent to the 3' side of the UAG triplet. Thus the interaction of tRNA with mRNA is influenced by mRNA

Lionello Bossi; John R. Roth

1980-01-01

228

Codon-anticodon interaction and the genetic code evolution.  

PubMed

The evolution of the genetic code, with 20 amino acids encoded from the beginning, is analyzed from the viewpoint of codon-anticodon interaction. Imposing a minimum principle for the interaction, in the framework of the so called crystal basis model of the genetic code, we determine the structure of the anticodons in the ancient, archetypal and early genetic codes, that are all reconciled in a unique frame. Most of our results agree with the generally accepted scheme. PMID:23438637

Sciarrino, A; Sorba, P

2013-02-21

229

A Synthetic Approach to Stop-Codon Scanning Mutagenesis  

PubMed Central

A general combinatorial mutagenesis strategy using common DMT-protected mononucleotide phosphoramidites and a single orthogonally-protected trinucleotide phosphoramidite (Fmoc-TAG) was developed to scan a gene with the TAG amber stop codon with complete synthetic control. In combination with stop-codon suppressors that insert natural (e.g., alanine) or unnatural (e.g., p-benzoylphenylalanine or Bpa) amino acids, a single DNA library can be used to incorporate different amino acids for diverse purposes. Here, we scanned TAG codons through part of the gene for a model four-helix bundle protein, Rop, which regulates the copy number of ColE1 plasmids. Alanine was incorporated into Rop for mapping its binding site using an in vivo activity screen, and subtle but important differences from in vitro gel-shift studies of Rop function are evident. As a test, Bpa was incorporated using a Phe14 amber mutant isolated from the scanning library. Surprisingly, Phe14Bpa Rop is weakly active, despite the critical role of Phe14 in Rop activity. Bpa is a photoaffinity label unnatural amino acid that can form covalent bonds with adjacent molecules upon UV irradiation. Irradiation of Phe14Bpa-Rop, which is a dimer in solution like wild-type Rop, results in covalent dimers, trimers and tetramers. This suggests that Phe14Bpa Rop weakly associates as a tetramer in solution and highlights the use of Bpa crosslinking as a means of trapping weak and transient interactions.

Nie, Lihua; Lavinder, Jason J.; Sarkar, Mohosin; Stephany, Kimberly; Magliery, Thomas J.

2011-01-01

230

Translational redefinition of UGA codons is regulated by selenium availability.  

PubMed

Incorporation of selenium into ~25 mammalian selenoproteins occurs by translational recoding whereby in-frame UGA codons are redefined to encode the selenium containing amino acid, selenocysteine (Sec). Here we applied ribosome profiling to examine the effect of dietary selenium levels on the translational mechanisms controlling selenoprotein synthesis in mouse liver. Dietary selenium levels were shown to control gene-specific selenoprotein expression primarily at the translation level by differential regulation of UGA redefinition and Sec incorporation efficiency, although effects on translation initiation and mRNA abundance were also observed. Direct evidence is presented that increasing dietary selenium causes a vast increase in ribosome density downstream of UGA-Sec codons for a subset of selenoprotein mRNAs and that the selenium-dependent effects on Sec incorporation efficiency are mediated in part by the degree of Sec-tRNA([Ser]Sec) Um34 methylation. Furthermore, we find evidence for translation in the 5'-UTRs for a subset of selenoproteins and for ribosome pausing near the UGA-Sec codon in those mRNAs encoding the selenoproteins most affected by selenium availability. These data illustrate how dietary levels of the trace element selenium can alter the readout of the genetic code to affect the expression of an entire class of proteins. PMID:23696641

Howard, Michael T; Carlson, Bradley A; Anderson, Christine B; Hatfield, Dolph L

2013-05-21

231

USAGE OF ESTONIAN OIL SHALE  

Microsoft Academic Search

Estonian oil shale has been used for 90 years mainly for electricity and oil generation with the ash being used for cement and light brick production. The oil shale usage has always been related to available mining and pro- cessing technology, and vice versa, with external influences of worldwide petroleum prices. The same situation is true today, when new technology

E. VÄLI; I. VALGMA; E. REINSALU

2008-01-01

232

Modeling educational usage of Facebook  

Microsoft Academic Search

The purpose of this study is to design a structural model explaining how users could utilize Facebook for educational purposes. In order to shed light on the educational usage of Facebook, in constructing the model, the relationship between users' Facebook adoption processes and their educational use of Facebook were included indirectly while the relationship between users' purposes in using Facebook

Sacide Güzin Mazman; Yasemin Koçak Usluel

2010-01-01

233

Users, Use, and Usage Statistics  

ERIC Educational Resources Information Center

For the August/September 2010 issue of "Library Technology Reports" (LTR) published by the American Library Association Techsource division, the author and her colleague, Rachel A. Fleming-May, focused on use and usage, both of electronic resources and use of libraries in general. In this article, the author discusses a few of the findings from an…

Grogg, Jill E.

2010-01-01

234

Marijuana usage and hypnotic susceptibility  

Microsoft Academic Search

Obtained anonymous self-reported drug usage data and Harvard Group Scale of Hypnotic Susceptibility scores from 282 college students. Frequent marihuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. There were no differences in primary suggestibility between principled nonusers and nonusers or between single-time, occasional, and frequent users. Frequent smoking of marihuana was significantly associated with S's

Louis R. Franzini; Roy D. McDonald

1973-01-01

235

Detecting differential usage of exons from RNA-seq data  

PubMed Central

RNA-seq is a powerful tool for the study of alternative splicing and other forms of alternative isoform expression. Understanding the regulation of these processes requires sensitive and specific detection of differential isoform abundance in comparisons between conditions, cell types, or tissues. We present DEXSeq, a statistical method to test for differential exon usage in RNA-seq data. DEXSeq uses generalized linear models and offers reliable control of false discoveries by taking biological variation into account. DEXSeq detects with high sensitivity genes, and in many cases exons, that are subject to differential exon usage. We demonstrate the versatility of DEXSeq by applying it to several data sets. The method facilitates the study of regulation and function of alternative exon usage on a genome-wide scale. An implementation of DEXSeq is available as an R/Bioconductor package.

Anders, Simon; Reyes, Alejandro; Huber, Wolfgang

2012-01-01

236

The initiation codon determines the efficiency but not the site of translation initiation in Chlamydomonas chloroplasts.  

PubMed Central

To study translation initiation in Chlamydomonas chloroplasts, we mutated the initiation codon AUG to AUU, ACG, ACC, ACU, and UUC in the chloroplast petA gene, which encodes cytochrome f of the cytochrome b6/f complex. Cytochrome f accumulated to detectable levels in all mutant strains except the one with a UUC codon, but only the mutant with an AUU codon grew well at 24 degrees C under conditions that require photosynthesis. Because no cytochrome f was detectable in the UUC mutant and because each mutant that accumulated cytochrome f did so at a different level, we concluded that any residual translation probably initiates at the mutant codon. As a further demonstration that alternative initiation sites are not used in vivo, we introduced in-frame UAA stop codons immediately downstream or upstream or in place of the initiation codon. Stop codons at or downstream of the initiation codon prevented accumulation of cytochrome f, whereas the one immediately upstream of the initiation codon had no effect on the accumulation of cytochrome f. These results suggest that an AUG codon is not required to specify the site of translation initiation in chloroplasts but that the efficiency of translation initiation depends on the identity of the initiation codon.

Chen, X; Kindle, K L; Stern, D B

1995-01-01

237

Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism  

Microsoft Academic Search

Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of

R. Medori; H. J. Tritschler

1993-01-01

238

Causes and effects of N-terminal codon bias in bacterial genes.  

PubMed

Most amino acids are encoded by multiple codons, and codon choice has strong effects on protein expression. Rare codons are enriched at the N terminus of genes in most organisms, although the causes and effects of this bias are unclear. Here, we measure expression from >14,000 synthetic reporters in Escherichia coli and show that using N-terminal rare codons instead of common ones increases expression by ~14-fold (median 4-fold). We quantify how individual N-terminal codons affect expression and show that these effects shape the sequence of natural genes. Finally, we demonstrate that reduced RNA structure and not codon rarity itself is responsible for expression increases. Our observations resolve controversies over the roles of N-terminal codon bias and suggest a straightforward method for optimizing heterologous gene expression in bacteria. PMID:24072823

Goodman, Daniel B; Church, George M; Kosuri, Sriram

2013-09-26

239

Synonymous Codon Ordering: A Subtle but Prevalent Strategy of Bacteria to Improve Translational Efficiency  

PubMed Central

Background In yeast coding sequences, once a particular codon has been used, subsequent occurrence of the same amino acid tends to use codons sharing the same tRNA. Such a phenomenon of co-tRNA codons pairing bias (CTCPB) is also found in some other eukaryotes but it is not known whether it occurs in prokaryotes. Methodology/Principal Findings In this study, we focused on a total of 773 bacterial genomes to investigate their synonymous codon pairing preferences. After calculating the actual frequencies of synonymous codon pairs and comparing them with their expected values, we detected an obvious pairing bias towards identical codon pairs. This seems consistent with the previously reported CTCPB phenomenon, since identical codons are certainly read by the same tRNA. However, among co-tRNA but non-identical codon pairs, only 22 were often found overrepresented, suggesting that many co-tRNA codons actually do not preferentially pair together in prokaryotes. Therefore, the previously reported co-tRNA codons pairing rule needs to be more rigorously defined. The affinity differences between a tRNA anticodon and its readable codons should be taken into account. Moreover, both within-gene-shuffling tests and phylogenetic analyses support the idea that translational selection played an important role in shaping the observed synonymous codon pairing pattern in prokaryotes. Conclusions Overall, a high level of synonymous codon pairing bias was detected in 73% investigated bacterial species, suggesting the synonymous codon ordering strategy has been prevalently adopted by prokaryotes to improve their translational efficiencies. The findings in this study also provide important clues to better understand the complex dynamics of translational process.

Shao, Zhu-Qing; Zhang, Yan-Mei; Feng, Xue-Ying; Wang, Bin; Chen, Jian-Qun

2012-01-01

240

Molecular Evolution between Drosophila Melanogaster and D. Simulans: Reduced Codon Bias, Faster Rates of Amino Acid Substitution, and Larger Proteins in D. Melanogaster  

PubMed Central

Both natural selection and mutational biases contribute to variation in codon usage bias within Drosophila species. This study addresses the cause of codon bias differences between the sibling species, Drosophila melanogaster and D. simulans. Under a model of mutation-selection-drift, variation in mutational processes between species predicts greater base composition differences in neutrally evolving regions than in highly biased genes. Variation in selection intensity, however, predicts larger base composition differences in highly biased loci. Greater differences in the G+C content of 34 coding regions than 46 intron sequences between D. melanogaster and D. simulans suggest that D. melanogaster has undergone a reduction in selection intensity for codon bias. Computer simulations suggest at least a fivefold reduction in N(e)s at silent sites in this lineage. Other classes of molecular change show lineage effects between these species. Rates of amino acid substitution are higher in the D. melanogaster lineage than in D. simulans in 14 genes for which outgroup sequences are available. Surprisingly, protein sizes are larger in D. melanogaster than in D. simulans in the 34 genes compared between the two species. A substantial fraction of silent, replacement, and insertion/deletion mutations in coding regions may be weakly selected in Drosophila.

Akashi, H.

1996-01-01

241

Electric household equipment and electric fuel usage in the Tri-State Region and the United States: 1960-70. Working paper  

Microsoft Academic Search

The possible impact of areawide residential location policy on future residential electricity usage in the Tri-State Metropolitan Region centering on New York City is investigated. This report is concerned with selected residential electric appliance usage in the Tri-State Region as compared with usage of these appliances across the United States between 1960 and 1970. Included are tabular representations of comparisons

1973-01-01

242

Chloroplast DNA codon use: Evidence for selection at the psb A locus based on tRNA availability  

Microsoft Academic Search

Codon use in the three sequenced chloroplast genomes (Marchantia, Oryza, and Nicotiana) is examined. The chloroplast has a bias in that codons NNA and NNT are favored over synonymous NNC and NNG codons. This appears to be a consequence of an overall high A + T content of the genome. This pattern of codon use is not followed by the

Brian R. Morton

1993-01-01

243

Distinct Paths To Stop Codon Reassignment by the Variant-Code Organisms Tetrahymena and Euplotes  

PubMed Central

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

Salas-Marco, Joe; Fan-Minogue, Hua; Kallmeyer, Adam K.; Klobutcher, Lawrence A.; Farabaugh, Philip J.; Bedwell, David M.

2006-01-01

244

WebUser: mining unexpected web usage  

Microsoft Academic Search

Web usage mining has been much concentrated on the discovery of relevant user behaviours from Web access record data. In this paper, we present WebUser, an approach to discover unexpected usage in Web access log. We present a belief-driven method for extracting unexpected Web usage sequences, where the belief system consists of a temporal relation and semantics constrained sequence rules

Anne Laurent; Pascal Poncelet

2009-01-01

245

The psbC start codon in Synechocystis sp. PCC 6803.  

PubMed

The translation start codon for psbC, the gene encoding CP43, a chlorophyll-binding protein of photosystem II, has been identified for the cyanobacterium Synechosystis sp. PCC 6803 using site-directed mutagenesis. An AUG codon, about 50 bases upstream from the end of psbD-I had previously been assumed to be the translation start site of psbC. However, the fact that the AUG codon is not present in psbC from several other organisms, whereas a GUG codon 14 bases upstream from the end of psbD-I is strictly conserved suggests that CP43 translation starts at the latter codon. Mutation of GUG, but not of AUG, led to a loss of CP43 and photoautotrophic growth, indicating that the GUG codon is the sole initiation site for translation of the CP43 protein in Synechocystis sp. PCC 6803. PMID:2105233

Carpenter, S D; Charite, J; Eggers, B; Vermaas, W F

1990-01-15

246

p53 codon 72 polymorphism and risk of cervical cancer.  

PubMed

Storey et al. (1998) implicated the proline/argine polymorphism of the codon 72 of the tumor-suppressor gene p53 in the development of cervical cancer (CC) with the observation that the p53 protein is more efficiently inactivated by the E6 oncoprotein of human papillomavirus in p53 arginine as compared with its proline isoform. These authors further noted that in the United Kingdom, individuals homozygous for the arginine allele were several times more susceptible to HPV-associated tumorigenesis that proline/arginine heterozygotes. Subsequent studies in different countries failed to unanimously confirm this association. Motivated by the high incidence of CC in Chile, we undertook a case control study obtaining the following frequencies for genotypes PP, AP and AA in 60 ICC cases and 53 carefully selected controls: 0.067, 0.250, 0.683 and 0.075, 0.453, 0.472 respectively. A significant difference (X2 = 3.19 p < 0.02) and an odds ratio of 2.62 supported Storey et al (1998)'s results. In addition, rejecting previous hypotheses about the world distribution of the p53 codon 72 polymorphism, we conclude that this distribution most likely represents ancient human dispersal routes. Several methodological and biological explanations for the results obtained in previous negative association studies are briefly discussed. PMID:14513722

Ojeda, José M; Ampuero, Sandra; Rojas, Patricio; Prado, Rodrigo; Allende, Jorge E; Barton, Sara A; Chakraborty, Ranajit; Rothhammer, Francisco

2003-01-01

247

Genome-wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae  

Microsoft Academic Search

In-frame stop codons normally signal termination during mRNA translation, but they can be read as 'sense' (readthrough) depending on their context, comprising the 6 nt preceding and following the stop codon. To identify novel contexts directing read- through, under-represented 50 and 30 stop codon con- texts from Saccharomyces cerevisiae were identified by genome-wide survey in silico. In contrast with the

I. Williams; J. Richardson; A. Starkey; I. Stansfield

2004-01-01

248

Rationalization and prediction of selective decoding of pseudouridine-modified nonsense and sense codons  

PubMed Central

A stop or nonsense codon is an in-frame triplet within a messenger RNA that signals the termination of translation. One common feature shared among all three nonsense codons (UAA, UAG, and UGA) is a uridine present at the first codon position. It has been recently shown that the conversion of this uridine into pseudouridine (?) suppresses translation termination, both in vitro and in vivo. Furthermore, decoding of the pseudouridylated nonsense codons is accompanied by the incorporation of two specific amino acids in a nonsense codon-dependent fashion. ? differs from uridine by a single N1H group at the C5 position; how ? suppresses termination and, more importantly, enables selective decoding is poorly understood. Here, we provide molecular rationales for how pseudouridylated stop codons are selectively decoded. Our analysis applies crystal structures of ribosomes in varying states of translation to consider weakened interaction of ? with release factor; thermodynamic and geometric considerations of the codon-anticodon base pairs to rank and to eliminate mRNA-tRNA pairs; the mechanism of fidelity check of the codon-anticodon pairing by the ribosome to evaluate noncanonical codon-anticodon base pairs and the role of water. We also consider certain tRNA modifications that interfere with the ?-coordinated water in the major groove of the codon-anticodon mini-helix. Our analysis of nonsense codons enables prediction of potential decoding properties for ?-modified sense codons, such as decoding ?UU potentially as Cys and Tyr. Our results provide molecular rationale for the remarkable dynamics of ribosome decoding and insights on possible reprogramming of the genetic code using mRNA modifications.

Parisien, Marc; Yi, Chengqi; Pan, Tao

2012-01-01

249

The codon-optimization of cfaE gene and evaluating its high expression capacity and conserved immunogenicity in Escherichia coli.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) is the most common cause of children diarrhea in the world. Adhesion of ETEC to small intestine is an important virulence trait. One of the most prevalent colonization factors (CFs) in human is CFA/I fimbriae and CfaE which is the required binding factor for adhesion of ETEC to intestinal mucosa. We optimized cfaE gene codons according to codon bias of E. coli to achieve a high level of recombinant protein expression. The optimized gene was expressed in E. coli and rCFaE protein was used for mice immunization. Blocking activity of the obtained antibody was examined by microplate agglutination inhibition test. SDS-PAGE analysis indicated that the optimized sequence of cfaE produces a suitable amount of rCFaE in comparison with native gene sequence. This optimized rCFaE protein could induces strong humoral response in mice and the antibody obtained against rCFaE inhibited the adhesion of ETEC to human group A erythrocytes. It is concluded that codon optimization is a useful approach for obtaining large quantities of recombinant rCFaE protein. With regard to the results of hemagglutination inhibition test, codon optimization and increased production of recombinant protein expressed in E. coli did not affect the immunogenicity potential of CFaE. PMID:23453276

Mansouri, Maysam; Mousavy, Seyed Jafar; Ehsaei, Zahra; Nazarian, Shahram; Zali, Mohammad Reza; Moazzeni, Seyed Mohammad

2013-02-28

250

Analysis of codon:anticodon interactions within the ribosome provides new insights into codon reading and the genetic code structure.  

PubMed Central

Although the decoding rules have been largely elucidated, the physical-chemical reasons for the "correctness" of codon:anticodon duplexes have never been clear. In this work, on the basis of the available data, we propose that the correct codon:anticodon duplexes are those whose formation and interaction with the ribosomal decoding center are not accompanied by uncompensated losses of hydrogen and ionic bonds. Other factors such as proofreading, base-base stacking and aminoacyl-tRNA concentration contribute to the efficiency and accuracy of aminoacyl-tRNA selection, and certainly these factors are important; but we suggest that analyses of hydrogen and ionic bonding alone provides a robust first-order approximation of decoding accuracy. Thus our model can simplify predictions about decoding accuracy and error. The model can be refined with data, but is already powerful enough to explain all of the available data on decoding accuracy. Here we predict which duplexes should be considered correct, which duplexes are responsible for virtually all misreading, and we suggest an evolutionary scheme that gave rise to the mixed boxes of the genetic code.

Lim, V I; Curran, J F

2001-01-01

251

Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism  

SciTech Connect

Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of French ancestry. Three family members who are under 40 years of age and who inherited the mutation showed only reduced perfusion in the basal ganglia on single photon emission computerized tomography. Some FFI features differ from the clinical and neuropathologic findings associated with 178[sup Asn] reported elsewhere. However, additional intragenic mutations accounting for the phenotypic differences were not observed in two affected individuals. In other sporadic and familial forms of Creutzfeldt-Jakob disease and Gerstmann-Straeussler syndrome, Met or Val homozygosity at polymorphic codon 129 is associated with a more severe phenotype, younger age at onset, and faster progression. In FFI, young and old individuals at disease onset had 129[sup Met/Val]. Moreover, of five 178[sup Asn] individuals who are above age-at-onset range and who are well, two have 129[sup Met] and three have 129[sup Met/Val], suggesting that polymorphic site 129 does not modulate FFI phenotypic expression. Genetic heterogeneity and environment may play an important role in inter- and intrafamilial variability of the 178[sup Asn] mutation. 32 refs., 5 figs., 1 tab.

Medori, R.; Tritschler, H.J. (Universita di Bologna (Italy))

1993-10-01

252

Henipavirus receptor usage and tropism.  

PubMed

Nipah (NiV) and Hendra (HeV) viruses are the deadliest human pathogens within the Paramyxoviridae family, which include human and animal pathogens of global biomedical importance. NiV and HeV infections cause respiratory and encephalitic illness with high mortality rates in humans. Henipaviruses (HNV) are the only Paramyxoviruses classified as biosafety level 4 (BSL4) pathogens due to their extreme pathogenicity, potential for bioterrorism, and lack of licensed vaccines and therapeutics. HNV use ephrin-B2 and ephrin-B3, highly conserved proteins, as viral entry receptors. This likely accounts for their unusually broad species tropism, and also provides opportunities to study how receptor usage, cellular tropism, and end-organ pathology relates to the pathobiology of HNV infections. The clinical and pathologic manifestations of NiV and HeV virus infections are reviewed in the chapters by Wong et al. and Geisbert et al. in this issue. Here, we will review the biology of the HNV receptors, and how receptor usage relates to HNV cell tropism in vitro and in vivo. PMID:22695915

Pernet, Olivier; Wang, Yao E; Lee, Benhur

2012-01-01

253

Henipavirus Receptor Usage and Tropism  

PubMed Central

Nipah (NiV) and Hendra (HeV) viruses are the deadliest human pathogens within the Paramyxoviridae family, which include human and animal pathogens of global biomedical importance. NiV and HeV infections cause respiratory and encephalitic illness with high mortality rates in humans. Henipaviruses (HNV) are the only paramyxoviruses classified as biosafety level 4 (BSL4) pathogens due to their extreme pathogenicity, potential for bioterrorism, and lack of licensed vaccines and therapeutics. HNV use ephrin-B2 and ephrin-B3, highly conserved proteins, as viral entry receptors. This likely accounts for their unusually broad species tropism, and also provides opportunities to study how receptor usage, cellular tropism, and end-organ pathology relates to the pathobiology of HNV infections. The clinical and pathologic manifestations of Nipah and Hendra virus infections are reviewed in the chapters by Wong et. al. and Geisbert et.al. in this issue. Here, we will review the biology of the henipavirus receptors, and how receptor usage relates to henipavirus cell tropism in vitro and in vivo.

Pernet, Olivier; Lee, Benhur

2013-01-01

254

Rapid detection of ethambutol-resistant Mycobacterium tuberculosis strains by PCR-RFLP targeting embB codons 306 and 497 and iniA codon 501 mutations  

Microsoft Academic Search

Mutations at embB gene codons 306 and 497 and iniA gene codon 501 occur frequently in ethambutol (EMB)-resistant Mycobacterium tuberculosis strains worldwide. The identification of these mutations in resistant strains has been achieved by labor-intensive DNA sequencing or by tedious amplification protocols followed by restriction endonuclease digestion. In this report, we describe PCR-restriction fragment length polymorphism (RFLP)-based methods for determining

S Ahmad; E Mokaddas; A.-A Jaber

2004-01-01

255

An Analysis of Anonymizer Technology Usage  

Microsoft Academic Search

Anonymity techniques provide legitimate usage such as privacy and freedom of speech, but are also used by cyber criminals to hide themselves. In this paper, we provide usage and geo-location analysis of major anonymization systems, i.e., anonymous proxy servers, remailers, JAP, I2P and Tor. Among these systems, remailers and JAP seem to have minimal usage. We then provide a detailed

Bingdong Li; Esra Erdin; Mehmet Hadi Gunes; George Bebis; Todd Shipley

2011-01-01

256

An Empirical Examination of the Utility of Codon-Substitution Models in Phylogeny Reconstruction  

Microsoft Academic Search

Models of codon substitution have been commonly used to compare protein-coding DNA sequences and are particularly effective in detecting signals of natural selection acting on the protein. Their utility in reconstructing molecular phylogenies and in dating species divergences has not been explored. Codon models naturally accommodate synonymous and nonsynonymous substitutions, which occur at very different rates and may be informative

Fengrong Ren; Hiroshi Tanaka; Ziheng Yang

2005-01-01

257

The codon preference plot: graphic analysis of protein coding sequences and prediction of gene expression.  

PubMed Central

The codon preference plot is useful for locating genes in sequenced DNA, predicting the relative level of their expression and for detecting DNA sequencing errors resulting in the insertion or deletion of bases within a coding sequence. The three possible reading frames are displayed in parallel along with the open reading frames and plots of the location of rare codons in each reading frame.

Gribskov, M; Devereux, J; Burgess, R R

1984-01-01

258

The translational stop signal: Codon with a context, or extended factor recognition element?  

Microsoft Academic Search

Wide ranging studies of the readthrough of translational stop codons within the last 25 years have suggested that the stop codon might be only part of the molecular signature for recognition of the termination signal. Such studies do not distinguish between effects on suppression and effects on termination, and so we have used a number of different approaches to deduce

W. P. Tate; E. S. Poole; M. E. Dalphin; L. L. Major; D. J. G. Crawford; S. A. Mannering

1996-01-01

259

Connection between stop codon reassignment and frequent use of shifty stop frameshifting  

Microsoft Academic Search

Ciliated protozoa of the genus Euplotes have undergone genetic code reassignment, redefining the termination codon UGA to encode cysteine. In addition, Euplotes spp. genes very frequently employ shifty stop frameshifting. Both of these phenomena involve noncanonical events at a termination codon, suggesting they might have a common cause. We recently demonstrated that Euplotes octocarinatus peptide release factor eRF1 ignores UGA

HARITHA VALLABHANENI; HUA FAN-MINOGUE; DAVID M. BEDWELL; PHILIP J. FARABAUGH

2009-01-01

260

Synonymous but not the same: the causes and consequences of codon bias  

Microsoft Academic Search

Despite their name, synonymous mutations have significant consequences for cellular processes in all taxa. As a result, an understanding of codon bias is central to fields as diverse as molecular evolution and biotechnology. Although recent advances in sequencing and synthetic biology have helped to resolve longstanding questions about codon bias, they have also uncovered striking patterns that suggest new hypotheses

Grzegorz Kudla; Joshua B. Plotkin

2010-01-01

261

Toward the experimental codon reassignment in vivo: protein building with an expanded amino acid repertoire  

Microsoft Academic Search

The high precision and fidelity of the genetic message transmission are ensured by numer- ous proofreading steps, from DNA replication and transcription to protein translation. The key event for translational fidelity is the proper codon assignment for 20 canonical amino acids. An experimental codon reassignment is possible for noncanonical amino ac- ids in vivo using artificially constructed expression hosts under

NEDILJKO BUDISA; CAROLINE MINKS; STEFAN ALEFELDER; WALTRAUD WENGER; FUMIN DONG; LUIS MORODER; ROBERT HUBER

262

Evolutionary conservation of codon optimality reveals hidden signatures of co-translational folding  

PubMed Central

The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to co-translational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that incorporates the competition between tRNA supply and demand. Applying this scale to ten closely related yeasts, we uncover the evolutionary conservation of codon optimality in eukaryotes. This analysis reveals universal patterns of conserved optimal and nonoptimal codons, often in clusters, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate co-translational polypeptide folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the co-translational folding of corresponding polypeptides.

Pechmann, Sebastian; Frydman, Judith

2012-01-01

263

Identification of amino acids responsible for stop codon recognition for polypeptide chain release factor.  

PubMed

One factor involved in eukaryotic translation termination is class 1 release factor in eukaryotes (eRF1), which functions to decode stop codons. Variant code species, such as ciliates, frequently exhibit altered stop codon recognition. Studies revealed that some class-specific residues in the eRF1 N-terminal domain are responsible for stop codon reassignment in ciliates. Here, we investigated the effects on stop codon recognition of chimeric eRF1s containing the N-terminal domain of Euplotes octocarinatus and Blepharisma japonicum eRF1 fused to Saccharomyces cerevisiae M and C domains using dual luciferase read-through assays. Mutation of class-specific residues in different eRF1 classes was also studied to identify key residues and motifs involved in stop codon decoding. As expected, our results demonstrate that 3 pockets within the eRF1 N-terminal domain were involved in decoding stop codon nucleotides. However, allocation of residues to each pocket was revalued. Our data suggest that hydrophobic and class-specific surface residues participate in different functions: modulation of pocket conformation and interaction with stop codon nucleotides, respectively. Residues conserved across all eRF1s determine the relative orientation of the 3 pockets according to stop codon nucleotides. However, quantitative analysis of variant ciliate and yeast eRF1 point mutants did not reveal any correlation between evolutionary conservation of class-specific residues and termination-related functional specificity and was limited in elucidating a detailed mechanism for ciliate stop codon reassignment. Thus, based on isolation of suppressor tRNAs from Euplotes and Tetrahymena, we propose that stop codon reassignment in ciliates may be controlled by cooperation between eRF1 and suppressor tRNAs. PMID:23668788

Xu, Lijun; Hao, Yanrong; Li, Cui; Shen, Quan; Chai, Baofeng; Wang, Wei; Liang, Aihua

2013-05-07

264

Physical Educators' Technology Competencies and Usage  

ERIC Educational Resources Information Center

|The purpose of this study was to examine K-12 physical education teachers' perceptions of ability and usage of technology. Physical educators (n = 114) completed the Physical Education Technology Usage Survey assessing their perceived technology competency, how and why they utilize technology, challenges they face in implementing technology, and…

Woods, Marianne L.; Goc Karp, Grace; Miao, Hui; Perlman, Dana

2008-01-01

265

Definite Article Usage across Varieties of English  

ERIC Educational Resources Information Center

|This paper seeks to explore the extent of definite article usage variation in several varieties of English based on a classification of its usage types. An annotation scheme based on Hawkins and Prince was developed for this purpose. Using matching corpus data representing Inner Circle varieties and Outer Circle varieties, analysis was made on…

Wahid, Ridwan

2013-01-01

266

Abnormal Web Usage Control by Proxy Strategies.  

ERIC Educational Resources Information Center

|Approaches to designing a proxy server with Web usage control and to making the proxy server effective on local area networks are proposed to prevent abnormal Web access and to prioritize Web usage. A system is implemented to demonstrate the approaches. The implementation reveals that the proposed approaches are effective, such that the abnormal…

Yu, Hsiang-Fu; Tseng, Li-Ming

2002-01-01

267

Policy Evolution in Distributed Usage Control  

Microsoft Academic Search

Usage control is a generalization of access control that also addresses how data is handled after it is released. Controlling the future usage of data includes controlling the future distribution of data. The evolution of policies upon re-distribution must hence be dened. Intuitively, clients should only strengthen policies associated with a data item when they re-distribute it. We provide a

Alexander Pretschner; Florian Schütz; Christian Schaefer; Thomas Walter

2009-01-01

268

The UCON ABC usage control model  

Microsoft Academic Search

In this paper, we introduce the family of UCONABC models for usage control (UCON), which integrate Authorizations (A), oBligations (B), and Conditions (C). We call these core models because they address the essence of UCON, leaving administration, delegation, and other important but second-order issues for later work. The term usage control is a generalization of access control to cover authorizations,

Jaehong Park; Ravi S. Sandhu

2004-01-01

269

A survey on usage of SQL  

Microsoft Academic Search

Relational database systems have been on market for more than a decade. SQL has been accepted as the standard query language of relational systems. To further understand the usage of relational systems and relational query language SQL, we conducted a survey recently that covers various aspects of the usage of SQL in industrial organizations. In this paper, we present those

Hongjun Lu; Hock Chuan Chan; Kwok Kee Wei

1993-01-01

270

Accelerated life tests at higher usage rates  

Microsoft Academic Search

Accelerated life tests are extensively used to provide quickly the information about the life distributions of products. Test units are subjected to elevated stresses which yield shorter lives. For some products whose life is defined by usage, e.g., mileage and cycles, test units are also run at higher usage rates (UR) to compress the test time. This paper presents a

Guangbin Yang

2005-01-01

271

Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk.  

PubMed

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymorphism at codon 198 of hGPX1 and lung cancer risk. Cases (n = 315) were matched to controls on age (+/-5 years), intervention group, and study clinic using incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1 Pro198Leu variant allele was 58% for controls and 71% for cases (P < 0.001). Using conditional logistic regression, we found a significant association between hGPX1 genotype and lung cancer risk. The odds ratio for heterozygotes was 1.8 (95% confidence interval, 1.2-2.8) and 2.3 (95% confidence interval, 1.3-3.8) for homozygous variants compared to wild-type individuals. Due to its high prevalence, the hGPX1 variant may contribute significantly to lung cancer risk among Caucasians but not among ethnic Chinese who do not exhibit this polymorphism. PMID:11103801

Ratnasinghe, D; Tangrea, J A; Andersen, M R; Barrett, M J; Virtamo, J; Taylor, P R; Albanes, D

2000-11-15

272

GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct  

PubMed Central

Background Activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Intraductal papillary neoplasms of the bile ducts (IPNBs) morphologically resemble pancreatic IPMNs. This study sought to assess the mutational status of GNAS at codon 201 in IPNBs. Methods Thirty-four patients were included. DNA from microdissected IPNBs was subjected to a polymerase chain reaction and ligation method for the detection of GNAS mutations at codon 201 and of KRAS mutations at codon 12. Mutational status was compared with clinical and pathologic data. Results The IPNBs had a median diameter of 3.5 cm and were located intrahepatically (n= 6), extrahepatically (n= 13), both intra- and extrahepatically (n= 4) or in the gallbladder (intracystic papillary neoplasms, n= 11). Most exhibited pancreatobiliary differentiation (n= 20), high-grade dysplasia (n= 26) and an associated adenocarcinoma (n= 20). Analysis of GNAS codon 201 identified only one mutant sample in a multifocal intestinal subtype intrahepatic IPNB with high-grade dysplasia. Six lesions harboured a KRAS codon 12 mutation. Conclusions GNAS codon 201 mutations are uncommon in IPNBs, by contrast with pancreatic IPMNs. More comprehensive molecular profiling is needed to uncover the pathways involved in IPNB development.

Matthaei, Hanno; Wu, Jian; Dal Molin, Marco; Debeljak, Marija; Lingohr, Philipp; Katabi, Nora; Klimstra, David S; Adsay, N Volkan; Eshleman, James R; Schulick, Richard D; Kinzler, Kenneth W; Vogelstein, Bert; Hruban, Ralph H; Maitra, Anirban

2012-01-01

273

Complete mitochondrial genome sequences of three bats species and whole genome mitochondrial analyses reveal patterns of codon bias and lend support to a basal split in Chiroptera.  

PubMed

Order Chiroptera is a unique group of mammals whose members have attained self-powered flight as their main mode of locomotion. Much speculation persists regarding bat evolution; however, lack of sufficient molecular data hampers evolutionary and conservation studies. Of ~1200 species, complete mitochondrial genome sequences are available for only eleven. Additional sequences should be generated if we are to resolve many questions concerning these fascinating mammals. Herein, we describe the complete mitochondrial genomes of three bats: Corynorhinus rafinesquii, Lasiurus borealis and Artibeus lituratus. We also compare the currently available mitochondrial genomes and analyze codon usage in Chiroptera. C. rafinesquii, L. borealis and A. lituratus mitochondrial genomes are 16438 bp, 17048 bp and 16709 bp, respectively. Genome organization and gene arrangements are similar to other bats. Phylogenetic analyses using complete mitochondrial genome sequences support previously established phylogenetic relationships and suggest utility in future studies focusing on the evolutionary aspects of these species. Comprehensive analyses of available bat mitochondrial genomes reveal distinct nucleotide patterns and synonymous codon preferences corresponding to different chiropteran families. These patterns suggest that mutational and selection forces are acting to different extents within Chiroptera and shape their mitochondrial genomes. PMID:22041054

Meganathan, P R; Pagan, Heidi J T; McCulloch, Eve S; Stevens, Richard D; Ray, David A

2011-10-24

274

Molecular Mechanism of Scanning and Start Codon Selection in Eukaryotes  

PubMed Central

Summary: The correct translation of mRNA depends critically on the ability to initiate at the right AUG codon. For most mRNAs in eukaryotic cells, this is accomplished by the scanning mechanism, wherein the small (40S) ribosomal subunit attaches to the 5? end of the mRNA and then inspects the leader base by base for an AUG in a suitable context, using complementarity with the anticodon of methionyl initiator tRNA (Met-tRNAiMet) as the key means of identifying AUG. Over the past decade, a combination of yeast genetics, biochemical analysis in reconstituted systems, and structural biology has enabled great progress in deciphering the mechanism of ribosomal scanning. A robust molecular model now exists, describing the roles of initiation factors, notably eukaryotic initiation factor 1 (eIF1) and eIF1A, in stabilizing an “open” conformation of the 40S subunit with Met-tRNAiMet bound in a low-affinity state conducive to scanning and in triggering rearrangement into a “closed” conformation incompatible with scanning, which features Met-tRNAiMet more tightly bound to the “P” site and base paired with AUG. It has also emerged that multiple DEAD-box RNA helicases participate in producing a single-stranded “landing pad” for the 40S subunit and in removing the secondary structure to enable the mRNA to traverse the 40S mRNA-binding channel in the single-stranded form for base-by-base inspection in the P site.

Hinnebusch, Alan G.

2011-01-01

275

Pyrrolysine is not hardwired for cotranslational insertion at UAG codons.  

PubMed

Pyrrolysine (Pyl), the 22nd naturally encoded amino acid, gets acylated to its distinctive UAG suppressor tRNA(Pyl) by the cognate pyrrolysyl-tRNA synthetase (PylRS). Here we determine the RNA elements required for recognition and aminoacylation of tRNA(Pyl) in vivo by using the Pyl analog N-epsilon-cyclopentyloxycarbonyl-l-lysine. Forty-two Methanosarcina barkeri tRNA(Pyl) variants were tested in Escherichia coli for suppression of the lac amber A24 mutation; then relevant tRNA(Pyl) mutants were selected to determine in vivo binding to M. barkeri PylRS in a yeast three-hybrid system and to measure in vitro tRNA(Pyl) aminoacylation. tRNA(Pyl) identity elements include the discriminator base, the first base pair of the acceptor stem, the T-stem base pair G51:C63, and the anticodon flanking nucleotides U33 and A37. Transplantation of the tRNA(Pyl) identity elements into the mitochondrial bovine tRNA(Ser) scaffold yielded chimeric tRNAs active both in vitro and in vivo. Because the anticodon is not important for PylRS recognition, a tRNA(Pyl) variant could be constructed that efficiently suppressed the lac opal U4 mutation in E. coli. These data suggest that tRNA(Pyl) variants may decode numerous codons and that tRNA(Pyl):PylRS is a fine orthogonal tRNA:synthetase pair that facilitated the late addition of Pyl to the genetic code. PMID:17360621

Ambrogelly, Alexandre; Gundllapalli, Sarath; Herring, Stephanie; Polycarpo, Carla; Frauer, Carina; Söll, Dieter

2007-02-20

276

18. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, BUILT 189x. ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, BUILT 189x. NOTE STRAIGHT ASHLAR COURSING AND RAISED KEYSTONES. VIEW NW. - Gettysburg National Military Park Tour Roads, Gettysburg, Adams County, PA

277

Genetic evidence for an androgen-regulated epididymal secretory glutathione peroxidase whose transcript does not contain a selenocysteine codon.  

PubMed Central

Epididymal glutathione peroxidase (GPX) has been suggested as a major factor in combating loss of fertility of spermatozoa due to lipid peroxidation. We report here the isolation and sequence of putative GPX cDNAs from rat (Rattus rattus) and cynomolgus-monkey (Macaca fascicularis) epididymis, which exhibit marked sequence identity with known GPXs. In both species the cDNAs encode predicted preproteins containing 221 amino acid residues. Unlike other characterized GPX sequences, epididymal GPX mRNA does not contain a selenocysteine codon (UGA). However, sequence comparison and molecular-modelling studies suggest a high degree of structural conservation between epididymal and other GPXs. Transcripts corresponding to epididymal GPX are not detected in a variety of other tissues (liver, spleen, kidney and testis) and appear to be androgen-regulated in the epididymis. Images Fig. 1. Fig. 2.

Perry, A C; Jones, R; Niang, L S; Jackson, R M; Hall, L

1992-01-01

278

Understanding Road Usage Patterns in Urban Areas  

PubMed Central

In this paper, we combine the most complete record of daily mobility, based on large-scale mobile phone data, with detailed Geographic Information System (GIS) data, uncovering previously hidden patterns in urban road usage. We find that the major usage of each road segment can be traced to its own - surprisingly few - driver sources. Based on this finding we propose a network of road usage by defining a bipartite network framework, demonstrating that in contrast to traditional approaches, which define road importance solely by topological measures, the role of a road segment depends on both: its betweeness and its degree in the road usage network. Moreover, our ability to pinpoint the few driver sources contributing to the major traffic flow allows us to create a strategy that achieves a significant reduction of the travel time across the entire road system, compared to a benchmark approach.

Wang, Pu; Hunter, Timothy; Bayen, Alexandre M.; Schechtner, Katja; Gonzalez, Marta C.

2012-01-01

279

Understanding Road Usage Patterns in Urban Areas  

NASA Astrophysics Data System (ADS)

In this paper, we combine the most complete record of daily mobility, based on large-scale mobile phone data, with detailed Geographic Information System (GIS) data, uncovering previously hidden patterns in urban road usage. We find that the major usage of each road segment can be traced to its own - surprisingly few - driver sources. Based on this finding we propose a network of road usage by defining a bipartite network framework, demonstrating that in contrast to traditional approaches, which define road importance solely by topological measures, the role of a road segment depends on both: its betweeness and its degree in the road usage network. Moreover, our ability to pinpoint the few driver sources contributing to the major traffic flow allows us to create a strategy that achieves a significant reduction of the travel time across the entire road system, compared to a benchmark approach.

Wang, Pu; Hunter, Timothy; Bayen, Alexandre M.; Schechtner, Katja; González, Marta C.

2012-12-01

280

Household Solvent Products: A National Usage Survey.  

National Technical Information Service (NTIS)

The study was conducted to provide usage information on 32 categories of common household and automotive products which were thought to contain methylene chloride or its substitutes. Respondents were selected using a random digit dialing procedure, were c...

D. Eisenhower

1987-01-01

281

Seat Belt Usage on School Buses.  

ERIC Educational Resources Information Center

Studies on seat belt usage conducted under contract with governmental organizations or prepared by professional societies, state and local organizations, and transportation specialists have made significant contributions, but none has successfully resolved the issue. (MLF)

Farmer, Ernest

1985-01-01

282

Usage Notes in the Oxford American Dictionary.  

ERIC Educational Resources Information Center

Compares the "Oxford American Dictionary" with the "American Heritage Dictionary." Examines the dictionaries' differences in philosophies of language, introductory essays, and usage notes. Concludes that the "Oxford American Dictionary" is too conservative, paternalistic, and dogmatic for the 1980s. (DMM)

Berner, R. Thomas

1981-01-01

283

The Construction and Usage of Simple Questionnaires.  

National Technical Information Service (NTIS)

This memorandum provides a brief guide to the construction and usage of simple questionnaires to collect opinions on various topics. Although it is devoted primarily to user trials of aircrew equipment, many of the principles discussed are common to other...

M. F. Allnutt C. B. Bolton

1975-01-01

284

Leakiness of termination codons in mitochondrial mutants of the yeast Saccharomyces cerevisiae  

Microsoft Academic Search

Seven mutants in exon 1 of the mitochondrial cob gene in yeast are described with respect to their translation products, RNA pattern, and deoxyribonucleotide sequence alteration(s). Sequence analysis of the mutations, which previously were shown to cause premature termination of apocytochrome b, revealed that two of them directly transform sense codons to chain-termination codons, whereas the other four are frame-shift

Brigitte Weiss-Brummer; Alexander Hiittenhofer; Fritz Kaudewitz

1984-01-01

285

Regional Codon Randomization: Defining a TATA-Binding Protein Surface Required for RNA Polymerase III Transcription  

Microsoft Academic Search

The TATA-binding protein (TBP) is required for transcription by all three nuclear RNA polymerases. TBP was subjected to regional codon randomization, a codon-based mutagenesis method that generates complex yet compact protein libraries. Analysis of 186 temperature-sensitive TBP mutants yielded 65 specifically defective in transcription by RNA polymerase III (Pol III). These mutants map to a limited TBP surface that may

Brendan P. Cormack; Kevin Struhl

1993-01-01

286

Doublet frequencies and codon weighting in the DNA of Escherichia coli and its phages  

Microsoft Academic Search

Summary A compilation of nucleic acid sequences fromE.coli and its phages has been analysed for the frequency of occurrence of nearest neighbour base doublets and codons. Several statistically significant deviations from random are found in both doublet and codon frequencies. The deviations inE.coli also appear to occur in ? and in the coat protein gene of MS2, whereas T4 and

R. A. Elton; G. J. Russell; J. H. Subak-Sharpe

1976-01-01

287

tRNA properties help shape codon pair preferences in open reading frames  

Microsoft Academic Search

Translation elongation is an accurate and rapid process, dependent upon efficient juxtaposition of tRNAs in the ribosomal A- and P-sites. Here, we sought evidence of A- and P-site tRNA interaction by examining bias in codon pair choice within open reading frames from a range of genomes. Three dis- tinct and marked effects were revealed once codon and dipeptide biases had

J. Ross Buchan; Lorna S. Aucott; Ian Stansfield

2006-01-01

288

tRNA proper ties help shape codon pair preferences in open reading frames  

Microsoft Academic Search

Translation elongation is an accurate and rapid process, dependent upon efficient juxtaposition of tRNAs in the ribosomal A- and P-sites. Here, we sought evidence of A- and P-site tRNA interaction by examining bias in codon pair choice within open reading frames from a range of genomes. Three dis- tinct and marked effects were revealed once codon and dipeptide biases had

J. Ross Buchan; Lorna S. Aucott; Ian Stansfield

289

Relationship Between p53 Codon 72 Polymorphism and Susceptibility to Sunburn and Skin Cancer  

Microsoft Academic Search

Upregulation of p53 protein induces either growth arrest or apoptosis in response to cellular injury This is signaled from a highly conserved p53 domain between codons 64 and 92, where a functional polymorphism results in either a proline (p53-72P) or an arginine (p53-72R) at codon 72. Preliminary studies suggest that p53-72R may be a risk factor for cervical cancer and,

Jane M. McGregor; Catherine A. Harwood; Louise Brooks; Sheila A. Fisher; Deirdre A. Kelly; Jenny O'nions; Antony R. Young; Thiru Surentheran; Judith Breuer; Thomas P. Millard; Cathryn M. Lewis; Irene M. Leigh; Alan Storey; Timothy Crook

2002-01-01

290

Codon reassignment and amino acid composition in hemichordate mitochondria (Balanoglossus carnosusycodon captureygenetic code changeyneutral theoryyprotein evolution)  

Microsoft Academic Search

In the mitochondrial genome of the hemi- chordate Balanoglossus carnosus, the codon AAA, which is assigned to lysine in most metazoans but to asparagine in echinoderms, is absent. Furthermore, the lysine tRNA gene carries an anticodon substitution that renders its gene prod- uct unable to decode AAA codons, whereas the asparagine tRNA gene has not changed to encode a tRNA

JOSE CASTRESANA; GERTRAUD FELDMAIER-FUCHS; SVANTE PAABO

291

Two-nucleotide codon change in a hemoglobin polymorphism of the Celebes black ape (Macaca nigra).  

PubMed

A hemoglobin polymorphism involving variant beta-chains was demonstrated in the Celebes black ape, Macaca nigra. Fingerprinting and amino acid analysis of the tryptic peptides from the two chain types have shown that they differ by a single amino acid substitution, between lysine and aspartic acid, which requires a two-nucleotide change in the corresponding codon. Another substitution in the same codon is found as a species between the black ape and that of other macaques. PMID:816351

Murata, M; Thompson, P E

1976-02-01

292

Genetic Polymorphism in p53 Codon 72 and Skin Cancer in Southwestern Taiwan  

Microsoft Academic Search

The Pro\\/Pro polymorphism of p53 codon 72 has been reported to be related to bladder and lung cancer, but its relationship with skin cancer is unclear. We assessed the hypothesis that there is a relationship between the p53 codon 72, Pro\\/Pro polymorphism, cumulative arsenic exposure, and the risk of skin cancer in a hospital-based case–control study in southwestern Taiwan. From

Yen-Ching Chen; Lilian Xu; Yu-Liang Leon Guo; Huey-Jen Jenny Su; Yu-Mei Hsueh; Thomas J. Smith; Louise M. Ryan; Meei-Shyuan Lee; Sheau-Chiou Chaor; Julia Yu-Yun Lee; David C. Christiani

2003-01-01

293

Female Athletes And Performance-Enhancer Usage  

Microsoft Academic Search

The purpose of this study was to develop a knowledge base on factors associated with performance-enhancer usage among female athletes at the high school level in order to identify markers for a future prevention-education program. The study used a pretest-only, between- subjects Likert Scale survey to rank the importance of internal and external pressures that may lead to performance-enhancer usage

Barbara K. Fralinger

2005-01-01

294

American Heritage Book of English Usage  

NSDL National Science Digital Library

This Web site takes visitors to the American Heritage Book of English Usage, which is a guide to current problems and debates in English language usage that will be valuable for native and non-native speakers alike. The work may be searched by keyword, or users may elect to browse through its 10 chapters. The subjects covered by the various chapters include gender, science terms, e-mail, word choice, and style.

2000-01-01

295

Recoding elements located adjacent to a subset of eukaryal selenocysteine-specifying UGA codons  

PubMed Central

Incorporation of the 21st amino acid, selenocysteine, into proteins is specified in all three domains of life by dynamic translational redefinition of UGA codons. In eukarya and archaea, selenocysteine insertion requires a cis-acting selenocysteine insertion sequence (SECIS) usually located in the 3?UTR of selenoprotein mRNAs. Here we present comparative sequence analysis and experimental data supporting the presence of a second stop codon redefinition element located adjacent to a selenocysteine-encoding UGA codon in the eukaryal gene, SEPN1. This element is sufficient to stimulate high-level (6%) translational redefinition of the SEPN1 UGA codon in human cells. Readthrough levels further increased to 12% when tested in the presence of the SEPN1 3?UTR SECIS. Directed mutagenesis and phylogeny of the sequence context strongly supports the importance of a stem loop starting six nucleotides 3? of the UGA codon. Sequences capable of forming strong RNA structures were also identified 3? adjacent to, or near, selenocysteine-encoding UGA codons in the Sps2, SelH, SelO, and SelT selenoprotein genes.

Howard, Michael T; Aggarwal, Gaurav; Anderson, Christine B; Khatri, Shikha; Flanigan, Kevin M; Atkins, John F

2005-01-01

296

Accumulation of a mRNA decay intermediate by ribosomal pausing at a stop codon.  

PubMed Central

A RNA fragment which is protected from degradation by ribosome pausing at a stop codon has been identified in growing Escherichia coli. The fragment is 261 nt long and corresponds to the 3'-end of the mRNA expressed from a semi-synthetic model gene. The 5'-end of the RNA fragment, denoted rpRNA (ribosomal pause RNA), is located 13 bases upstream of the stop codon. In vivo decay of the complete mRNA and accumulation of rpRNA are dependent on the nature of the stop codon and its codon context. The data indicate that the rpRNA fragment arises from interrupted decay of the S3A'mRNA in the 5'-->m3'direction, in connection with a ribosomal pause at the stop codon. RF-2 decoding of UGA is less efficient than RF-1 decoding of UAG in identical codon contexts, as judged from rpRNA steady-state levels. The half-life of UGA-containing rpRNAs is at least 5 min, indicating that ribosomal pausing can be a major factor in stabilising downstream regions of messenger RNAs.

Bjornsson, A; Isaksson, L A

1996-01-01

297

E-Book Usage and the "Choice" Outstanding Academic Book List: Is There a Correlation?  

ERIC Educational Resources Information Center

|In this study, the staff of the library at Auburn University at Montgomery analyzed circulation patterns for electronic books in the fields of Political Science, Public Administration and Law to see if favorable "Choice" reviews can be used to predict usage of electronic books. A comparison of the circulations between print and electronic books…

Carter Williams, Karen; Best, Rickey

2006-01-01

298

E-Book Usage and the "Choice" Outstanding Academic Book List: Is There a Correlation?  

ERIC Educational Resources Information Center

In this study, the staff of the library at Auburn University at Montgomery analyzed circulation patterns for electronic books in the fields of Political Science, Public Administration and Law to see if favorable "Choice" reviews can be used to predict usage of electronic books. A comparison of the circulations between print and electronic books…

Carter Williams, Karen; Best, Rickey

2006-01-01

299

Print and Electronic Resources: Usage Statistics at Guru Gobind Singh Indraprastha University Library  

ERIC Educational Resources Information Center

|Purpose: The purpose of this paper is to quantify the use of electronic journals in comparison with the print collections in the Guru Gobind Singh Indraprastha University Library. Design/methodology/approach: A detailed analysis was made of the use of lending services, the Xerox facility and usage of electronic journals such as Science Direct,…

Kapoor, Kanta

2010-01-01

300

SBP, SECIS binding protein, binds to the RNA fragment upstream of the Sec UGA codon in glutathione peroxidase mRNA  

Microsoft Academic Search

In mammals, most of the selenium contained in the body is present as an unusual amino acid, selenocysteine (Sec), whose codon is UGA. Because the UGA codon is typically recognized as a translation stop signal, it is intriguing how a cell recognizes and distinguishes a UGA Sec codon from a UGA stop codon. For eukaryotic selenoprotein mRNAs, it has been

Takaharu Mizutani; Toshinobu Fujiwara

2000-01-01

301

Identification of eRF1 residues that play critical and complementary roles in stop codon recognition  

PubMed Central

The initiation and elongation stages of translation are directed by codon–anticodon interactions. In contrast, a release factor protein mediates stop codon recognition prior to polypeptide chain release. Previous studies have identified specific regions of eukaryotic release factor one (eRF1) that are important for decoding each stop codon. The cavity model for eukaryotic stop codon recognition suggests that three binding pockets/cavities located on the surface of eRF1's domain one are key elements in stop codon recognition. Thus, the model predicts that amino acid changes in or near these cavities should influence termination in a stop codon-dependent manner. Previous studies have suggested that the TASNIKS and YCF motifs within eRF1 domain one play important roles in stop codon recognition. These motifs are highly conserved in standard code organisms that use UAA, UAG, and UGA as stop codons, but are more divergent in variant code organisms that have reassigned a subset of stop codons to sense codons. In the current study, we separately introduced TASNIKS and YCF motifs from six variant code organisms into eRF1 of Saccharomyces cerevisiae to determine their effect on stop codon recognition in vivo. We also examined the consequences of additional changes at residues located between the TASNIKS and YCF motifs. Overall, our results indicate that changes near cavities two and three frequently mediated significant effects on stop codon selectivity. In particular, changes in the YCF motif, rather than the TASNIKS motif, correlated most consistently with variant code stop codon selectivity.

Conard, Sara E.; Buckley, Jessica; Dang, Mai; Bedwell, Gregory J.; Carter, Richard L.; Khass, Mohamed; Bedwell, David M.

2012-01-01

302

JSTOR usage data and what it can tell us about ourselves: is there predictability based on historical use by libraries of similar size?  

Microsoft Academic Search

Purpose – Sets out to explore what effects institutional size and the selections of JSTOR collections have on the overall (total) usage statistics. Design\\/methodology\\/approach – This is a preliminary report of JSTOR use made by five academic libraries of similar size and scale; a sixth smaller campus is used to contrast\\/support findings. A comparison study of the five institutions' usage

Barbara J. Gauger; Carolyn Kacena

2006-01-01

303

Tracking Resource Usage Using Heterogeneous Feature Spaces with Local Exceptions  

Microsoft Academic Search

We describe a method for tracking usage of resources in a web environment by representing the resources as a feature space in which usage instances appear as trails, so that common access patterns are shown as similar trails. To improve the analysis of usage data, prior knowledge about usage patterns can be specified by the server admin- istrator as local

Tilmann Steinberg; James Ford; Yi Ouyang; Li Shen; Yuhang Wang; Wei Zheng; Fillia Makedon

304

NovAtel's Novel Approach to CPU Usage Measurement  

Microsoft Academic Search

SUMMARY This paper describes a set of CPU usage analysis tools, named CPU Probes, with the benefits of both hardware and software tools, and few of their disadvantages. CPU probes use a serial line unit or programmable interval timer as a clock to sample the CPU usage of a system, resulting in fast and accurate CPU usage estimates. CPU usage

David R. Crowe

1991-01-01

305

A Dynamic Usage Modelling Approach to Software Reliability Engineering  

Microsoft Academic Search

In software reliability engineering, reliability models have been in focus for years, while less attention has been given to usage models, which are necessary for usage based testing. The state hierarchy usage model is designed to capture the complex and dynamic usage behav- iour for large real-time software systems, for example telecommunica- tion systems. It provides a practical approach to

P. Runeson; C. Wohlin

1998-01-01

306

Usage Impact Factor: the effects of sample characteristics on usage-based impact metrics  

Microsoft Academic Search

There exist ample demonstrations that indicators of scholarly impact analogous to the citation-based ISI Im- pact Factor can be derived from usage data; however, so far, usage can practically be recorded only at the level of distinct information services. This leads to community- specific assessments of scholarly impact that are diffi- cult to generalize to the global scholarly community. In

Johan Bollen; Herbert Van De Sompel

2006-01-01

307

EBSCO's Usage Consolidation Attempts to Streamline Gathering, Storage, and Reporting of Usage Statistics  

ERIC Educational Resources Information Center

|This paper provides an overview of EBSCO's new Usage Consolidation product designed to streamline the harvesting, storage, and analysis of usage statistics from electronic resources. Strengths and weaknesses of the product are discussed as well as an early beta partner's experience. In the current atmosphere of flat or declining budgets,…

Remy, Charlie

2012-01-01

308

EBSCO's Usage Consolidation Attempts to Streamline Gathering, Storage, and Reporting of Usage Statistics  

ERIC Educational Resources Information Center

This paper provides an overview of EBSCO's new Usage Consolidation product designed to streamline the harvesting, storage, and analysis of usage statistics from electronic resources. Strengths and weaknesses of the product are discussed as well as an early beta partner's experience. In the current atmosphere of flat or declining budgets, libraries…

Remy, Charlie

2012-01-01

309

Non-universal decoding of the leucine codon CUG in several Candida species.  

PubMed Central

It has been reported that CUG, a universal leucine codon, is read as serine in an asporogenic yeast, Candida cylindracea. The distribution of this non-universal genetic code in various yeast species was studied using an in vitro translation assay system with a synthetic messenger RNA containing CUG codons in-frame. It was found that CUG is used as a serine codon in six out of the fourteen species examined, while it is used for leucine in the remaining eight. The tRNA species responsible for the translation of codon CUG as serine was detected in all the six species in which CUG is translated as serine. The grouping according to the CUG codon assignments in these yeast species shows a good correlation with physiological classification by the chain lengths of the isoprenoid moiety of ubiquinone and the cell-wall sugar contained in the yeasts. The six Candida species examined in which CUG is used as serine belong to one distinct group in Hemiascomycetes.

Ohama, T; Suzuki, T; Mori, M; Osawa, S; Ueda, T; Watanabe, K; Nakase, T

1993-01-01

310

Connection between stop codon reassignment and frequent use of shifty stop frameshifting  

PubMed Central

Ciliated protozoa of the genus Euplotes have undergone genetic code reassignment, redefining the termination codon UGA to encode cysteine. In addition, Euplotes spp. genes very frequently employ shifty stop frameshifting. Both of these phenomena involve noncanonical events at a termination codon, suggesting they might have a common cause. We recently demonstrated that Euplotes octocarinatus peptide release factor eRF1 ignores UGA termination codons while continuing to recognize UAA and UAG. Here we show that both the Tetrahymena thermophila and E. octocarinatus eRF1 factors allow efficient frameshifting at all three termination codons, suggesting that UGA redefinition also impaired UAA/UAG recognition. Mutations of the Euplotes factor restoring a phylogenetically conserved motif in eRF1 (TASNIKS) reduced programmed frameshifting at all three termination codons. Mutation of another conserved residue, Cys124, strongly reduces frameshifting at UGA while actually increasing frameshifting at UAA/UAG. We will discuss these results in light of recent biochemical characterization of these mutations.

Vallabhaneni, Haritha; Fan-Minogue, Hua; Bedwell, David M.; Farabaugh, Philip J.

2009-01-01

311

ProxiMAX randomization: a new technology for non-degenerate saturation mutagenesis of contiguous codons.  

PubMed

Back in 2003, we published 'MAX' randomization, a process of non-degenerate saturation mutagenesis using exactly 20 codons (one for each amino acid) or else any required subset of those 20 codons. 'MAX' randomization saturates codons located in isolated positions within a protein, as might be required in enzyme engineering, or else on one face of an ?-helix, as in zinc-finger engineering. Since that time, we have been asked for an equivalent process that can saturate multiple contiguous codons in a non-degenerate manner. We have now developed 'ProxiMAX' randomization, which does just that: generating DNA cassettes for saturation mutagenesis without degeneracy or bias. Offering an alternative to trinucleotide phosphoramidite chemistry, ProxiMAX randomization uses nothing more sophisticated than unmodified oligonucleotides and standard molecular biology reagents. Thus it requires no specialized chemistry, reagents or equipment, and simply relies on a process of saturation cycling comprising ligation, amplification and digestion for each cycle. The process can encode both unbiased representation of selected amino acids or else encode them in predefined ratios. Each saturated position can be defined independently of the others. We demonstrate accurate saturation of up to 11 contiguous codons. As such, ProxiMAX randomization is particularly relevant to antibody engineering. PMID:24059507

Ashraf, Mohammed; Frigotto, Laura; Smith, Matthew E; Patel, Seema; Hughes, Marcus D; Poole, Andrew J; Hebaishi, Husam R M; Ullman, Christopher G; Hine, Anna V

2013-10-01

312

ProxiMAX randomization: a new technology for non-degenerate saturation mutagenesis of contiguous codons  

PubMed Central

Back in 2003, we published ‘MAX’ randomization, a process of non-degenerate saturation mutagenesis using exactly 20 codons (one for each amino acid) or else any required subset of those 20 codons. ‘MAX’ randomization saturates codons located in isolated positions within a protein, as might be required in enzyme engineering, or else on one face of an ?-helix, as in zinc-finger engineering. Since that time, we have been asked for an equivalent process that can saturate multiple contiguous codons in a non-degenerate manner. We have now developed ‘ProxiMAX’ randomization, which does just that: generating DNA cassettes for saturation mutagenesis without degeneracy or bias. Offering an alternative to trinucleotide phosphoramidite chemistry, ProxiMAX randomization uses nothing more sophisticated than unmodified oligonucleotides and standard molecular biology reagents. Thus it requires no specialized chemistry, reagents or equipment, and simply relies on a process of saturation cycling comprising ligation, amplification and digestion for each cycle. The process can encode both unbiased representation of selected amino acids or else encode them in predefined ratios. Each saturated position can be defined independently of the others. We demonstrate accurate saturation of up to 11 contiguous codons. As such, ProxiMAX randomization is particularly relevant to antibody engineering.

Ashraf, Mohammed; Frigotto, Laura; Smith, Matthew E.; Patel, Seema; Hughes, Marcus D.; Poole, Andrew J.; Hebaishi, Husam R.M.; Ullman, Christopher G.; Hine, Anna V.

2013-01-01

313

Motivations and usage patterns of Weibo.  

PubMed

Referred to as "Weibo," microblogging in China has witnessed an exponential growth. In addition to the Twitter-like functionality, Weibo allows rich media uploads into user feeds, provides threaded comments, and offers applications, games, and Weibo medals. This expanded functionality, as well as the observed differences in trending content, suggests potentially different user motivations to join Weibo and their usage patterns compared to Twitter. This pioneering study identifies dominant Weibo user motivations and their effects on usage patterns. We discuss the findings of an online survey of 234 Weibo users and suggest managerial implications and future research directions. PMID:22703037

Zhang, Lixuan; Pentina, Iryna

2012-06-01

314

NAT Usage in Residential Broadband Networks  

NASA Astrophysics Data System (ADS)

Many Internet customers use network address translation (NAT) when connecting to the Internet. To understand the extend of NAT usage and its implications, we explore NAT usage in residential broadband networks based on observations from more than 20,000 DSL lines. We present a unique approach for detecting the presence of NAT and for estimating the number of hosts connected behind a NAT gateway using IP TTLs and HTTP user-agent strings. Furthermore, we study when each of the multiple hosts behind a single NAT gateway is active. This enables us to detect simultaneous use. In addition, we evaluate the accuracy of NAT analysis techniques when fewer information is available.

Maier, Gregor; Schneider, Fabian; Feldmann, Anja

315

Association of sporadic Creutzfeldt–Jakob disease with homozygous genotypes at PRNP codons 129 and 219 in the Korean population  

Microsoft Academic Search

Human prion protein gene (PRNP) is considered an important gene in determining the incidence of human transmissible spongiform encephalopathies or prion\\u000a diseases. Polymorphisms of PRNP at codon 129 in Europeans and codon 219 in Japanese may play an important role in the susceptibility to sporadic Creutzfeldt–Jakob\\u000a disease (CJD); data regarding codon 129 in the Japanese population have led to divergent

Byung-Hoon Jeong; Kyung-Hee Lee; Nam-Ho Kim; Jae-Kwang Jin; Jae-Il Kim; Richard I. Carp; Yong-Sun Kim

2005-01-01

316

Decoding the Decoding Region: Analysis of Eukaryotic Release Factor (eRF1) Stop Codon-Binding Residues  

Microsoft Academic Search

Peptide synthesis in eukaryotes terminates when eukaryotic release factor 1 (eRF1) binds to an mRNA stop codon and occupies the ribosomal A site. Domain 1 of the eRF1 protein has been implicated in stop codon recognition in a number of experimental studies. In order to further pinpoint the residues of this protein involved in stop codon recognition, we sequenced and

Han Liang; Jonathan Y. Wong; Qing Bao; Andre R. O. Cavalcanti; Laura F. Landweber

2005-01-01

317

Tentoxin sensitivity of chloroplasts determined by codon 83 of beta subunit of proton-ATPase.  

PubMed

Tentoxin is a naturally occurring phytotoxic peptide that causes seedling chlorosis and arrests growth in sensitive plants and algae. In vitro, it inhibits activity of the beta subunit of the plastid proton-adenosine triphosphatase (ATPase) from sensitive species. Plastid atpB genes from six closely related, tentoxin-sensitive or -resistant Nicotiana species differ at codon 83, according to their response to the toxin: glutamate correlated with resistance and aspartate correlated with sensitivity. The genetic relevance of this site was confirmed in Chlamydomonas reinhardtii by chloroplast transformation. The alga, normally tentoxin-resistant, was rendered tentoxin-sensitive by mutagenesis of its plastid atpB gene at codon 83. Codon 83 may represent a critical site on the beta subunit that does not compete with nucleotide binding or other catalytic activities. PMID:1387730

Avni, A; Anderson, J D; Holland, N; Rochaix, J D; Gromet-Elhanan, Z; Edelman, M

1992-08-28

318

Business Intelligence from Web Usage Mining  

Microsoft Academic Search

The rapid e-commerce growth has made both business community and customers face a new situation. Due to intense competition on the one hand and the customer's option to choose from several alternatives, the business com- munity has realized the necessity of intelligent marketing strategies and relationship management. Web usage mining attempts to discover useful knowledge from the secondary data obtained

Ajith Abraham

2004-01-01

319

Collaborative Portfolio's Effect on Library Usage  

ERIC Educational Resources Information Center

Library resources are expensive and it is the library media specialist's responsibility to ensure that use of the library's resources is maximized to support the School Strategic Plan (SSP). This library usage study examined data on the scheduling of high school classes for research-based assignments, related to content area curriculum standards,…

Bryan, Valerie

2011-01-01

320

Web usage mining with intentional browsing data  

Microsoft Academic Search

Many researches have developed Web usage mining (WUM) algorithms utilizing Web log records in order to discover useful knowl- edge to be used in supporting business applications and decision making. The quality of WUM in knowledge discovery, however, depends on the algorithm as well as on the data. This research explores a new data source called intentional browsing data (IBD)

Yu-hui Tao; Tzung-pei Hong; Yu-ming Su

2008-01-01

321

Production, Usage, and Comprehension in Animal Vocalizations  

ERIC Educational Resources Information Center

|In this review, we place equal emphasis on production, usage, and comprehension because these components of communication may exhibit different developmental trajectories and be affected by different neural mechanisms. In the animal kingdom generally, learned, flexible vocal production is rare, appearing in only a few orders of birds and few…

Seyfarth, Robert M.; Cheney, Dorothy L.

2010-01-01

322

Safety Belt Usage Survey in Kentucky, 2011.  

National Technical Information Service (NTIS)

The objective of this study was to establish 2011 safety belt and child safety seat usage rates in Kentucky. The 2011 survey continues to document the results after enactment of the original 'secondary enforcement' statewide mandatory Safety belt law in 1...

E. R. Green K. R. Agent

2011-01-01

323

Google Scholar Usage: An Academic Library's Experience  

ERIC Educational Resources Information Center

|Google Scholar is a free service that provides a simple way to broadly search for scholarly works and to connect patrons with the resources libraries provide. The researchers in this study analyzed Google Scholar usage data from 2006 for three library tools at San Francisco State University: SFX link resolver, Web Access Management proxy server,…

Wang, Ya; Howard, Pamela

2012-01-01

324

Nutrition label usage of Chinese consumers  

Microsoft Academic Search

Though the Pacific-rim countries like China, Hong Kong and ASEAN countries will soon constitute an economic power comparable to that of North America and Europe, most of the empirical work on food labelling is related to the US and UK consumers. Research into nutrition label usage in a Chinese socio-cultural context is not found. To redress this imbalance, this study

Wai-sum Siu; Tina Man-yi Tsoi

1998-01-01

325

Exploring Cognition Change of Skype Usage  

Microsoft Academic Search

With the exponential growth of the Internet usage, Internet applications are widespread enormously across almost every field, but very few of them actually survive in the market. Among them, the Internet phone service, which has been available since 1995, has fast advanced in terms of offering new value-added services and acquiring an impressive increase in the number of users from

Yung-Chih Yen; Chia-Chen Yen; Jih-Shih Hsu

2008-01-01

326

Google Scholar Usage: An Academic Library's Experience  

Microsoft Academic Search

Google Scholar is a free service that provides a simple way to broadly search for scholarly works and to connect patrons with the resources libraries provide. The researchers in this study analyzed Google Scholar usage data from 2006 for three library tools at San Francisco State University: SFX link resolver, Web Access Management proxy server, and ILLiad interlibrary loan server.

Ya Wang; Pamela Howard

2012-01-01

327

Mammography Usage and the Health Belief Model  

Microsoft Academic Search

Regular screening mammograms for asymptomatic women are the most effective method for early detection of breast cancer. This study assessed the relative influence of Health Belief Model (HBM) constructs on prior mammography usage and the intention to obtain mammograms with data from a sample of 1,057 women over the age of 35 years residing in an urban community in the

Judith A. Stein; Sarah A. Fox; Paul J. Murata; Donald E. Morisky

1992-01-01

328

Google Scholar Usage: An Academic Library's Experience  

ERIC Educational Resources Information Center

Google Scholar is a free service that provides a simple way to broadly search for scholarly works and to connect patrons with the resources libraries provide. The researchers in this study analyzed Google Scholar usage data from 2006 for three library tools at San Francisco State University: SFX link resolver, Web Access Management proxy server,…

Wang, Ya; Howard, Pamela

2012-01-01

329

An overview of anonymity technology usage  

Microsoft Academic Search

Abstract Anonymity technologies enable Internet users to maintain a level of privacy that prevents the collection of identifying information such as the IP address. Understanding the deployment of anonymity technologies on the Internet is important to analyze the current and future trends. In this paper, we provide a tutorial survey and a measurement study to understand the anonymity technology usage

Bingdong Li; Esra Erdin; Mehmet Hadi Gunes; George Bebis; Todd Shipley

2013-01-01

330

Métamorphe: augmenting hotkey usage with actuated keys  

Microsoft Academic Search

Hotkeys are an efficient method of selecting commands on a keyboard. However, these shortcuts are often underused by users. We present Métamorphe, a novel keyboard with keys that can be individually raised and lowered to promote hotkeys usage. Métamorphe augments the output of traditional keyboards with haptic and visual feedback, and offers a novel design space for user input on

Gilles Bailly; Daniel Wigdor

2013-01-01

331

An audit of first generation cephalosporin usage  

Microsoft Academic Search

Cefadroxil is a semi-synthetic first generation oral cephalosporin with advantages of almost 100% excretion in the urine within six hours and low cost. It was freely available in the formulary and we undertook an audit of its usage, the indications cited, underlying clinical conditions and relevant microbiology in 106 cases. Following the audit, cefadroxil was restricted, available only on the

N. Shetty; R. I. Shulmant; G. M. Scott

1999-01-01

332

Formal Methods Reality Check: Industrial Usage  

Microsoft Academic Search

Based on a systematic survey and analysis of the use of formal methods in the development of a dozen industrial applications, we summarize the methods being used, characterize the styles of industrial usage, and provide recommendations for evolutionary enhancements to the technology base of formal methods. The industrial applications ranged from reverse engineering to system certification; code scale ranges from

Dan Craigen; Susan L. Gerhart; Ted Ralston

1995-01-01

333

A Tool for Web Usage Mining  

Microsoft Academic Search

This paper presents a tool for web usage mining. The aim is centered on providing a tool that facilitates the mining process rather than implement elaborated algorithms and techniques. The tool covers difierent phases of the CRISP-DM methodology as data preparation, data selection, modeling and evaluation. The algorithms used in the modeling phase are those implemented in the Weka project.

José M. Domenech; Javier Lorenzo

2007-01-01

334

Usages of DASH for rich media services  

Microsoft Academic Search

In recent years, audio-visual distribution over Internet has witnessed the growing usage of HTTP based delivery systems. While these systems have their drawbacks for some use-cases, they also have many advantages, the most important one being reusing the existing delivery infrastructure such as HTTP servers, proxies and caches. The MPEG group has started the standardization of the Dynamic Adaptive Streaming

Cyril Concolato; Jean Le Feuvre; Romain Bouqueau

2011-01-01

335

Female Athletes and Performance-Enhancer Usage  

ERIC Educational Resources Information Center

|The purpose of this study was to develop a knowledge base on factors associated with performance-enhancer usage among female athletes at the high school level in order to identify markers for a future prevention-education program. The study used a pretest-only, between-subjects Likert Scale survey to rank the importance of internal and external…

Fralinger, Barbara K.; Pinto-Zipp, Genevieve; Olson, Valerie; Simpkins, Susan

2007-01-01

336

Prediction of Low Vision Aid Usage.  

ERIC Educational Resources Information Center

Use of 11 kinds of visual aids by 458 clients of an Israel low vision clinic was evaluated by age, sex, work status, participation in a rehabilitation program, academic status, number of visual aids in use, and number of diagnosed eye diseases. Usage prediction was found to be complex and highly differentiated. (Author/JDD)

Eaglstein, A.; Rapaport, S.

1991-01-01

337

Patterns of Drug Usage among Vietnam Veterans.  

National Technical Information Service (NTIS)

A factor analysis was performed on an intercorrelation matrix of reported drug usage frequencies for seven drug categories at two consecutive periods of time. Subjects were 1,010 Army Vietnam veterans in pay grade E6 or below, aged 26 years or less. Retro...

A. H. Fisher K. E. Nelson J. Panzarella

1972-01-01

338

Fossil fuel usage and the environment  

Microsoft Academic Search

The Greenhouse Effect and global warming, ozone formation in the troposphere, ozone destruction in the stratosphere, and acid rain are important environmental issues. The relationship of fossil fuel usage to some of these issues is discussed. Data on fossil fuel consumption and the sources and sinks of carbon dioxide, carbon monoxide, methane, nitrogen and sulfur oxides, and ozone indicate that

Klass

1990-01-01

339

Comparison of Bandwidth Usage: Service Location Protocol and Jini  

Microsoft Academic Search

Recently there has been an increase in the development of tech- nologies for resource discovery, since for example, resources such as printers, mail boxes, memory space, and disk space are available in every network, ready to be used for any host. This has been caused, in part, by the growth in the popularity of portable devices such as laptops, PDAs,

Javier Govea; Michel Barbeau

2000-01-01

340

Synonymous but not the same: the causes and consequences of codon bias  

PubMed Central

Despite their name, synonymous mutations have significant consequences for cellular processes in all taxa. As a result, an understanding of codon bias is central to fields as diverse as molecular evolution and biotechnology. Although recent advances in sequencing and synthetic biology have helped resolve longstanding questions about codon bias, they have also uncovered striking patterns that suggest new hypotheses about protein synthesis. Ongoing work to quantify the dynamics of initiation and elongation is as important for understanding natural synonymous variation as it is for designing transgenes in applied contexts.

Plotkin, Joshua B.; Kudla, Grzegorz

2010-01-01

341

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

PubMed Central

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. Images

Grant, C M; Hinnebusch, A G

1994-01-01

342

p53 codon 72 polymorphism in patients with gastric and colorectal cancer in a Korean population  

Microsoft Academic Search

Background  The common p53 codon 72 polymorphism has been investigated as a risk factor for cancer in different populations; however,\\u000a the results have been inconsistent. This study investigated the risk of developing gastric or colorectal cancer associated\\u000a with the p53 codon 72 polymorphism in a Korean population.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We conducted a large-scale case–control study that included 2,213 gastric cancer patients; 1,829 colorectal

Hye-Rim Song; Sun-Seog Kweon; Hee Nam Kim; Jin-Mei Piao; Woo-Jun Yun; Jin-Su Choi; Jun-Eul Hwang; Ju-Young Yoon; Hyeong-Rok Kim; Young-Kyu Park; Soo-Hyun Kim; Yoo-Duk Choi; Min-Ho Shin

343

Comparing internet and mobile phone usage: digital divides of usage, adoption, and dropouts  

Microsoft Academic Search

Results from a national representative telephone survey of Americans in 2000 show that Internet and mobile phone usage was very similar, and that several digital divides exist with respect to both Internet and mobile phone usage. The study identifies and analyzes three kinds of digital divides for both the Internet and mobile phones—users\\/nonuser, veteran\\/recent, and continuing\\/dropout—and similarities and differences among

Ronald E. Rice; James E. Katz

2003-01-01

344

Steady-state levels of imported tRNAs in Chlamydomonas mitochondria are correlated with both cytosolic and mitochondrial codon usages  

Microsoft Academic Search

The mitochondrial genome of Chlamydomonas reinhardtii only encodes three expressed tRNA genes, thus most mitochondrial tRNAs are likely imported. The sharing of tRNAs between chloro- plasts and mitochondria has been speculated in this organism. We first demonstrate that no plasti- dial tRNA is present in mitochondria and that the mitochondrial translation mainly relies on the import of nucleus-encoded tRNA species.

Elizaveta Vinogradova; Thalia Salinas; Valerie Cognat; Claire Remacle; Laurence Marechal-Drouard

2009-01-01

345

The mitochondrial genome sequence of the ciliate Paramecium caudatum reveals a shift in nucleotide composition and codon usage within the genus Paramecium  

Microsoft Academic Search

Background  Despite the fact that the organization of the ciliate mitochondrial genome is exceptional, only few ciliate mitochondrial\\u000a genomes have been sequenced until today. All ciliate mitochondrial genomes are linear. They are 40 kb to 47 kb long and contain\\u000a some 50 tightly packed genes without introns. Earlier studies documented that the mitochondrial guanine + cytosine contents\\u000a are very different between

Dana Barth; Thomas U Berendonk

2011-01-01

346

Evolutionary Adaptation of the Amino Acid and Codon Usage of the Mosquito Sodium Channel following Insecticide Selection in the Field Mosquitoes  

PubMed Central

Target site insensitivity resulting from point mutations within the voltage-gated sodium channel of the insect nervous system is known to be of primary importance in the development of resistance to pyrethroid insecticides. This study shifts current research paradigms by conducting, for the first time, a global analysis of all the naturally occurring mutations, both nonsynonymous and synonymous mutations, as well as mutation combinations in the entire mosquito sodium channel of Culex quinquefasciatus and analyzing their evolutionary and heritable feature and roles in insecticide resistance. Through a systematic analysis of comparing nucleotide polymorphisms in the entire sodium channel cDNAs of individuals between susceptible and resistant mosquito strains, between field parental mosquitoes and their permethrin selected offspring, and among different mosquito groups categorized by their levels of tolerance to specific permethrin concentrations within and among the mosquito strains of the field parental strains and their permethrin selected offspring, 3 nonsynonymous (A109S, L982F, and W1573R) and 6 synonymous (L852, G891, A1241, D1245, P1249, and G1733) mutations were identified. The co-existence of all 9 mutations, both nonsynonymous and synonymous, and their homozygousity were found to be important factors for high levels of resistance. Our study, for the first time, provide a strong case demonstrating the co-existence of both nonsynonymous and synonymous mutations in the sodium channel of resistant mosquitoes in response to insecticide resistance and the inheritance of these mutations in the offspring of field mosquito strains following insecticide selection.

Xu, Qiang; Zhang, Lee; Li, Ting; Zhang, Lan; He, Lin; Dong, Ke; Liu, Nannan

2012-01-01

347

PCR-RFLP to Detect Codon 248 Mutation in Exon 7 of "p53" Tumor Suppressor Gene  

ERIC Educational Resources Information Center

|Individual genome DNA was extracted fast from oral swab and followed up with PCR specific for codon 248 of "p53" tumor suppressor gene. "Msp"I restriction mapping showed the G-C mutation in codon 248, which closely relates to cancer susceptibility. Students learn the concepts, detection techniques, and research significance of point mutations or…

Ouyang, Liming; Ge, Chongtao; Wu, Haizhen; Li, Suxia; Zhang, Huizhan

2009-01-01

348

Does the prion protein gene 129 codon polymorphism influence sleep? Evidence from a fatal familial insomnia kindred  

Microsoft Academic Search

Objective: Experimental and clinical evidence in prion diseases suggests that the prion protein gene (PRNP) plays a role in regulating sleep.Methods: Seventeen healthy individuals belonging to a single fatal familial insomnia pedigree, 8 carriers and 9 non-carriers of the PRNP codon 178 mutation, underwent polysomnography and spectral electroencephalographic (EEG) analysis. All were also characterized with regard to the codon 129

Giuseppe Plazzi; Pasquale Montagna; Manolo Beelke; Lino Nobili; Fabrizio De Carli; Pietro Cortelli; Stefano Vandi; Patrizia Avoni; Paolo Tinuper; Pierluigi Gambetti; Elio Lugaresi; Franco Ferrillo

2002-01-01

349

Identification and Repair of Positive Binding Antibodies Containing Randomly Generated Amber Codons from Synthetic Phage Display Libraries  

Microsoft Academic Search

Phage display technology allows for the rapid isolation and characterization of monoclonal antibodies that have vast potential for therapeutic and diagnostic applications. However, the panning process, which utilizes a host strain that suppresses termination by the amber codon, has an inherent bias toward clones containing randomly generated amber stop codons, complicating identification of positive binding antibodies when the antibody genes

Warren D. Marcus; Stuart M. Lindsay; Michael R. Sierks

2006-01-01

350

The significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas  

PubMed Central

Infection with the human papillomavirus is an important co-factor in the development of cervical carcinomas. Accordingly, HPV DNA is recognised in most of these tumours. Polymorphism of the p53 gene, codon 72, is also considered a risk factor in the development of cervical carcinoma. However, this finding is contradicted by several observers. In the present investigation, 111 cases of adenocarcinoma of the cervix collected through the Swedish Cancer Registry and 188 controls (females with normal cytology at organised gynaecological screening) were analysed with regard to p53, codon 72, polymorphism using a PCR- and SSCP-based technique. In the controls, 9% showed pro/pro, 44% pro/arg and 47% arg/arg, whereas in the invasive adenocarcinomas, the corresponding figures were 0%, 29% and 71%, respectively. The difference was statistically significant (P = 0.001). HPV DNA was identified in 86 tumours (HPV 18 in 48, HPV 16 in 31 and HPV of unknown type in 7 cases) and 25 tumours were HPV negative. The p53, codon 72, genotypes observed in HPV-positive and HPV-negative cervical adenocarcinomas were not statistically different (P = 0.690). The results indicate that women homozygotic for arg/arg in codon 72 of the p53 gene are at an increased risk for the development of cervical adenocarcinomas. However, this genetic disposition seems to be unrelated to the HPV infection. © 2001 Cancer Research Campaign??http://www.bjcancer.com

Andersson, S; Rylander, E; Strand, A; Sallstrom, J; Wilander, E

2001-01-01

351

The KIT Exon 11 Stop Codon Mutation in Gastrointestinal Stromal Tumors: What Is the Clinical Meaning?  

PubMed Central

Background/Aims Gastrointestinal stromal tumors (GISTs) strongly express a receptor tyrosine kinase (RTK, c-KIT-CD117) harboring a KIT mutation that causes constitutive receptor activation leading to the development and growth of tumors; 35% of GISTs without KIT mutations have platelet-derived growth factor receptor alpha (PDGFRA) mutations, and the type of mutation plays an important role in the response to treatment. This study aimed to establish the frequency of stop codon mutations in the RTKs, KIT, and PDGFRA, in GISTs and correlate this molecular alteration with protein expression and treatment responsiveness. Methods Seventy-nine GISTs were analyzed for both KIT and PDGFRA mutations. Immunohistochemical expression was studied in tissue microarray blocks. Results We found three rare KIT mutations in exon 11 that induced a stop codon, two at position 563 and one at position 589, which have never been described before. All three tumors were CD117-, DOG1-, and CD34-positive. Two patients with a KIT stop codon mutation did not respond to imatinib therapy and died shortly after treatment. Conclusions The association between stop codon mutations in KIT and patient survival, if confirmed in a larger population, may be useful in choosing effective therapies.

Michelucci, Angela; Chiappetta, Caterina; Cacciotti, Jessica; Veccia, Norman; Astri, Elisa; Leopizzi, Martina; Prosperi Porta, Romana; Petrozza, Vincenzo; Della Rocca, Carlo; Bevilacqua, Generoso; Cavazzana, Andrea

2013-01-01

352

Unusual base pairing during the decoding of a stop codon by the ribosome.  

PubMed

During normal translation, the binding of a release factor to one of the three stop codons (UGA, UAA or UAG) results in the termination of protein synthesis. However, modification of the initial uridine to a pseudouridine (?) allows efficient recognition and read-through of these stop codons by a transfer RNA (tRNA), although it requires the formation of two normally forbidden purine-purine base pairs. Here we determined the crystal structure at 3.1?Å resolution of the 30S ribosomal subunit in complex with the anticodon stem loop of tRNA(Ser) bound to the ?AG stop codon in the A site. The ?A base pair at the first position is accompanied by the formation of purine-purine base pairs at the second and third positions of the codon, which show an unusual Watson-Crick/Hoogsteen geometry. The structure shows a previously unsuspected ability of the ribosomal decoding centre to accommodate non-canonical base pairs. PMID:23812587

Fernández, Israel S; Ng, Chyan Leong; Kelley, Ann C; Wu, Guowei; Yu, Yi-Tao; Ramakrishnan, V

2013-06-30

353

Expanded use of sense codons is regulated by modified cytidines in tRNA.  

PubMed

Codon use among the three domains of life is not confined to the universal genetic code. With only 22 tRNA genes in mammalian mitochondria, exceptions from the universal code are necessary for proper translation. A particularly interesting deviation is the decoding of the isoleucine AUA codon as methionine by the one mitochondrial-encoded tRNA(Met). This tRNA decodes AUA and AUG in both the A- and P-sites of the metazoan mitochondrial ribosome. Enrichment of posttranscriptional modifications is a commonly appropriated mechanism for modulating decoding rules, enabling some tRNA functions while restraining others. In this case, a modification of cytidine, 5-formylcytidine (f(5)C), at the wobble position-34 of human mitochondrial tRNA(f5CAU)(Met) (hmtRNA(f5CAU)(Met)) enables expanded decoding of AUA, resulting in a deviation in the genetic code. Visualization of the codon•anticodon interaction by X-ray crystallography revealed that recognition of both A and G at the third position of the codon occurs in the canonical Watson-Crick geometry. A modification-dependent shift in the tautomeric equilibrium toward the rare imino-oxo tautomer of cytidine stabilizes the f(5)C34•A base pair geometry with two hydrogen bonds. PMID:23781103

Cantara, William A; Murphy, Frank V; Demirci, Hasan; Agris, Paul F

2013-06-18

354

Codon conservation in the influenza A virus genome defines RNA packaging signals  

Microsoft Academic Search

Genome segmentation facilitates reassortment and rapid evolution of influenza A virus. However, segmentation complicates particle assembly as virions must contain all eight vRNA species to be infectious. Specific packaging signals exist that extend into the coding regions of most if not all segments, but these RNA motifs are poorly defined. We measured codon variability in a large dataset of sequences

Julia R. Gog; Emmanuel Dos Santos Afonso; Rosa M. Dalton; India Leclercq; Laurence Tiley; Debra Elton; Johann C. von Kirchbach; Nadia Naffakh; Nicolas Escriou; Paul Digard

2007-01-01

355

Genetic diversity of mango cultivars estimated using Start Codon Targeted (SCoT) markers  

Technology Transfer Automated Retrieval System (TEKTRAN)

Diversity and genetic relationships among 23 mango germplasm accessions, collected from different locations in Guangxi province in China, were analyzed by using a novel and simple gene targeted DNA marker: Start Codon Targeted (SCoT) markers. This technique uses a single, 18-mer primer PCR amplifica...

356

Codon optimization of bacterial luciferase ( lux ) for expression in mammalian cells  

Microsoft Academic Search

Expression of the bacterial luciferase (lux) system in mammalian cells would culminate in a new generation of bioreporters for in vivo monitoring and diagnostics technology. Past efforts to express bacterial luciferase in mammalian cells have resulted in only modest gains due in part to low overall expression of the bacterial genes. To optimize expression, we have designed and synthesized codon-optimized

Stacey S. Patterson; Hebe. M. Dionisi; Rakesh K. Gupta; Gary S. Sayler

2005-01-01

357

Differences in codon bias cannot explain differences in translational power among microbes  

Microsoft Academic Search

BACKGROUND: Translational power is the cellular rate of protein synthesis normalized to the biomass invested in translational machinery. Published data suggest a previously unrecognized pattern: translational power is higher among rapidly growing microbes, and lower among slowly growing microbes. One factor known to affect translational power is biased use of synonymous codons. The correlation within an organism between expression level

Les Dethlefsen; Thomas M. Schmidt

2005-01-01

358

p53 Codon 72 Arg Homozygotes Are Associated with an Increased Risk of Cutaneous Melanoma  

Microsoft Academic Search

The p53 gene plays an important role in cell cycle control, facilitating DNA repair activities in response to DNA damage. Aberrant cell cycle control impairs DNA repair and increases the probability of mutations that can lead to carcinogenesis. The p53 gene is polymorphic at codon 72 (Arg\\/Pro) of its protein, which is functionally distinct, leading to inquiry into its role

Hongbing Shen; Zhensheng Liu; Sara S. Strom; Margaret R. Spitz; Jeffrey E. Lee; Jeffrey E. Gershenwald; Merrick I. Ross; Paul F. Mansfield; Madeleine Duvic; Honnavara N. Ananthaswamy; Qingyi Wei

2003-01-01

359

7 CFR 97.700 - Public interest in wide usage.  

Code of Federal Regulations, 2010 CFR

...false Public interest in wide usage. 97.700 Section 97...LABORATORY TESTING PROGRAMS PLANT VARIETY AND PROTECTION Public...700 Public interest in wide usage. (a) If the Secretary...shall refer the matter to the Plant Variety Protection Board...

2010-01-01

360

7 CFR 97.700 - Public interest in wide usage.  

Code of Federal Regulations, 2010 CFR

...false Public interest in wide usage. 97.700 Section 97...LABORATORY TESTING PROGRAMS PLANT VARIETY AND PROTECTION Public...700 Public interest in wide usage. (a) If the Secretary...shall refer the matter to the Plant Variety Protection Board...

2009-01-01

361

Monitoring the usage of a computer system  

SciTech Connect

Controlling the usage of computer systems particularly those operated for the federal government, is an important topic today. Audit requirements have grown to the point where they can be a significant burden to the proprietors of the system. The paper briefly mentions several proposals for responding to increased audit requirements and for monitoring a system to detect unauthorized activity. A technique is proposed for situations where the proscribed or the intended activity can be characterized in terms of program or system performance parameters. The design of a usage monitoring system is outlined. The design is based on enhancing the audit data provided by the monitored system, capturing the audit data in a separate system to protect it from user access, and implementing one of the audit trail analysis systems currently under development.

Bailey, D.J.

1987-11-01

362

Historical review of medicinal plants' usage  

PubMed Central

Healing with medicinal plants is as old as mankind itself. The connection between man and his search for drugs in nature dates from the far past, of which there is ample evidence from various sources: written documents, preserved monuments, and even original plant medicines. Awareness of medicinal plants usage is a result of the many years of struggles against illnesses due to which man learned to pursue drugs in barks, seeds, fruit bodies, and other parts of the plants. Contemporary science has acknowledged their active action, and it has included in modern pharmacotherapy a range of drugs of plant origin, known by ancient civilizations and used throughout the millennia. The knowledge of the development of ideas related to the usage of medicinal plants as well as the evolution of awareness has increased the ability of pharmacists and physicians to respond to the challenges that have emerged with the spreading of professional services in facilitation of man's life.

Petrovska, Biljana Bauer

2012-01-01

363

Business Intelligence from Web Usage Mining  

Microsoft Academic Search

Abstract. The rapid e-commerce growth has made,both business community and customers face a new situation. Due to intense competition on the one hand and the customer’s option to choose from several alternatives, the business community has realized the necessity of intelligent marketing strategies and relationship management. Web usage mining attempts to discover useful knowledge from the secondary data obtained from

Ajith Abraham

2003-01-01

364

Teacher and student usage of science textbooks  

Microsoft Academic Search

This study examines the differences between teachers' and students' perceptions of textbook usage in the science classroom.\\u000a Four categories of use were identified: teacher directed student activities; teaching\\/studying guidance; as a source of information\\u000a for the user and as preparation for assessment. The results of the study show that differences do occur between teachers and\\u000a students with respect to their

David Tulip; Alan Cook

1993-01-01

365

Usage-style centered research for creative product design  

Microsoft Academic Search

The purpose of this paper is to present systemic creative product design methods based on usage-style. According to the basic meanings of usage-style, the logical hierarchical structure of usage-style was outlined and established. Combining with product design principle, this work focused on the product values system and product structure system, established the design frameworks of `value forming from usage-style' and

Wu Zhi-jun; Li Liang-zhi; Na Cheng-ai; Xing Jiang-hao

2009-01-01

366

UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota  

PubMed Central

The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNAGlyUCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNAGlyUCA with glycine in vitro with similar activity compared with normal tRNAGlyUCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNAGlyUCA in Escherichia coli yields significant ?-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.

Campbell, James H.; O'Donoghue, Patrick; Campbell, Alisha G.; Schwientek, Patrick; Sczyrba, Alexander; Woyke, Tanja; Soll, Dieter; Podar, Mircea

2013-01-01

367

TrimerDimer: an oligonucleotide-based saturation mutagenesis approach that removes redundant and stop codons  

PubMed Central

9-fluorenylmethoxycarbonyl (Fmoc) and 4,4?-dimethoxytrityl (DMTr) are orthogonal hydroxyl protecting groups that have been used in conjunction to assemble oligonucleotide libraries whose variants contain wild-type and mutant codons randomly interspersed throughout a focused DNA region. Fmoc is labile to organic bases and stable to weak acids, whereas DMTr behaves oppositely. Based on these chemical characteristics, we have now devised TrimerDimer, a novel codon-based saturation mutagenesis approach that removes redundant and stop codons during the assembly of degenerate oligonucleotides. In this approach, five DMTr-protected trinucleotide phosphoramidites (dTGG, dATG, dTTT, dTAT and dTGC) and five Fmoc-protected dinucleotide phosphoramidites (dAA, dTT, dAT, dGC and dCG) react simultaneously with a starting oligonucleotide growing on a solid support. The Fmoc group is then removed and the incorporated dimers react with a mixture of three DMTr-protected monomer phosphoramidites (dC, dA and dG) to produce 15 trinucleotides: dCAA, dAAA, dGAA, dCTT, dATT, dGTT, dCAT, dAAT, dGAT, dCGC, dAGC, dGGC, dCCG, dACG and dGCG. After one mutagenic cycle, 20 codons are generated encoding the 20 natural amino acids. TrimerDimer was tested by randomizing the four contiguous codons that encode amino acids L64–G67 of an engineered, nonfluorescent GFP protein. Sequencing of 89 nonfluorescent mutant clones and isolation of two fluorescent mutants confirmed the principle.

Gaytan, Paul; Contreras-Zambrano, Casandra; Ortiz-Alvarado, Monica; Morales-Pablos, Alfredo; Yanez, Jorge

2009-01-01

368

TrimerDimer: an oligonucleotide-based saturation mutagenesis approach that removes redundant and stop codons.  

PubMed

9-fluorenylmethoxycarbonyl (Fmoc) and 4,4'-dimethoxytrityl (DMTr) are orthogonal hydroxyl protecting groups that have been used in conjunction to assemble oligonucleotide libraries whose variants contain wild-type and mutant codons randomly interspersed throughout a focused DNA region. Fmoc is labile to organic bases and stable to weak acids, whereas DMTr behaves oppositely. Based on these chemical characteristics, we have now devised TrimerDimer, a novel codon-based saturation mutagenesis approach that removes redundant and stop codons during the assembly of degenerate oligonucleotides. In this approach, five DMTr-protected trinucleotide phosphoramidites (dTGG, dATG, dTTT, dTAT and dTGC) and five Fmoc-protected dinucleotide phosphoramidites (dAA, dTT, dAT, dGC and dCG) react simultaneously with a starting oligonucleotide growing on a solid support. The Fmoc group is then removed and the incorporated dimers react with a mixture of three DMTr-protected monomer phosphoramidites (dC, dA and dG) to produce 15 trinucleotides: dCAA, dAAA, dGAA, dCTT, dATT, dGTT, dCAT, dAAT, dGAT, dCGC, dAGC, dGGC, dCCG, dACG and dGCG. After one mutagenic cycle, 20 codons are generated encoding the 20 natural amino acids. TrimerDimer was tested by randomizing the four contiguous codons that encode amino acids L64-G67 of an engineered, nonfluorescent GFP protein. Sequencing of 89 nonfluorescent mutant clones and isolation of two fluorescent mutants confirmed the principle. PMID:19783828

Gaytán, Paul; Contreras-Zambrano, Casandra; Ortiz-Alvarado, Mónica; Morales-Pablos, Alfredo; Yáñez, Jorge

2009-09-25

369

A Structural Equation Model for ICT Usage in Higher Education  

ERIC Educational Resources Information Center

|This study focuses on Information and Communication Technologies (ICT) usage, which is the indicator of diffusion. A model composed of the variables which can explain ICT usage in Turkish higher education is established and tested within the study. The two dimensions of ICT usage are considered: instructional and managerial. The data collected…

Usluel, Yasemin Kocak; Askar, Petek; Bas, Turgay

2008-01-01

370

Factors motivating and affecting health information exchange usage  

PubMed Central

Objective Health information exchange (HIE) is the process of electronically sharing patient-level information between providers. However, where implemented, reports indicate HIE system usage is low. The aim of this study was to determine the factors associated with different types of HIE usage. Design Cross-sectional analysis of clinical data from emergency room encounters included in an operational HIE effort linked to system user logs using crossed random-intercept logistic regression. Measurements Independent variables included factors indicative of information needs. System usage was measured as none, basic usage, or a novel pattern of usage. Results The system was accessed for 2.3% of all encounters (6142 out of 271?305). Novel usage patterns were more likely for more complex patients. The odds of HIE usage were lower in the face of time constraints. In contrast to expectations, system usage was lower when the patient was unfamiliar to the facility. Limitations Because of differences between HIE efforts and the fact that not all types of HIE usage (ie, public health) could be included in the analysis, results are limited in terms of generalizablity. Conclusions This study of actual HIE system usage identifies patients and circumstances in which HIE is more likely to be used and factors that are likely to discourage usage. The paper explores the implications of the findings for system redesign, information integration across exchange partners, and for meaningful usage criteria emerging from provisions of the Health Information Technology for Economic & Clinical Health Act.

Zhao, Hongwei; Jaspserson, 'Jon; Gamm, Larry D; Ohsfeldt, Robert L

2011-01-01

371

Burnout and Humor Usage among Community College Nursing Faculty Members.  

ERIC Educational Resources Information Center

Assesses the correlation of burnout among community college nursing faculty members and their use of humor to mediate academic stress related to burnout. Differences in burnout between high versus low humor usage respondents showed a higher sense of personal accomplishment with high humor usage. Of those with low humor usage, workload was related…

Talbot, Laura A.

2000-01-01

372

Internet Acceptable Usage Policy: Arguments and Perils 1  

Microsoft Academic Search

Organisations are now aware of the need to control employee usage of the Internet. An Internet acceptable usage policy contains guidelines for employees indicating both acceptable and unacceptable Internet usages, with the intention of controlling employee behaviours and actions which contribute to the incidence and severity of the organisation's Internet risks. This paper explores the arguments for an organisationa l

Sharman Lichtenstein; Paula M. C. Swatman

1997-01-01

373

How to write a proper Internet usage policy  

Microsoft Academic Search

Increased usage of the Internet at work has prompted organisations to write Internet Usage Policies to establish appropriate use. This article addresses the main components of an Internet Usage Policy, including security, monitoring and filtering, privacy rights, intellectual property, organisation representation, acceptable personal use, unacceptable personal use, investigation of violations and corrective action, and notification of policy. Each section explains

Brad Welebir; Brian H. Kleiner

2005-01-01

374

Reviewing and Critiquing Computer Learning and Usage Among Older Adults  

Microsoft Academic Search

By searching the keywords of “older adult” and “computer” in ERIC, Academic Search Premier, and PsycINFO, this study reviewed 70 studies published after 1990 that address older adults' computer learning and usage. This study revealed 5 prominent themes among reviewed literature: (a) motivations and barriers of older adults' usage of computers, (b) age-related differences in computer learning and usage, (c)

Young Sek Kim

2008-01-01

375

Following the crowd:social influence and technology usage  

Microsoft Academic Search

This study examined the impact of social influence theory on distance education technology (DET) usage. Delineation of university culture types conceptualized by Bergquist (the collegial culture, the managerial culture, the developmental culture, and the negotiating culture) were also examined in relation to technology usage. This study tested the proposed relationships in a survey of distance education technology usage at a

Sharon L. Segrest; Darla J. Domke-Damonte; Angela K. Miles; William P. Anthony

1998-01-01

376

XRCC1 codon 399 and ERCC2 codon 751 polymorphism, smoking, and drinking and risk of esophageal squamous cell carcinoma in a North Indian population.  

PubMed

XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementing group 2) codon 751 polymorphisms were studied in esophageal squamous cell carcinoma (ESQCC) in a North Indian population. Peripheral blood samples of 120 cases and 160 age-and-gender matching controls were collected from North India and the two polymorphisms were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques. The data were analyzed with a logistic regression model. The XRCC1 codon 399 Gln/Gln genotype was significantly associated with reduced risk of ESQCC (OR = 0.31, 95% CI = 0.12-0.78, P = 0.01). In smokers, the XRCC1 Arg/Gln genotype was marginally and statistically nonsignificantly (OR = 1.5) associated with increased risk of this cancer. In drinkers, the XRCC1 Gln/Gln genotype was significantly protective (OR = 0.06, 95% CI = 0.007-0.605, P = 0.03), whereas ERCC2 (Lys/Gln-Gln/Gln) was marginally associated with increased risk (OR = 2.1, 95% CI = 0.46-9.44). Upon analysis of gene-gene interaction, a relationship was observed, although statistically nonsignificant, between combined genotypes of XRCC1 (Arg/Gln-Gln/Gln)-ERCC2 Gln/Gln (OR = 0.33, 95% CI = 0.09-1.16) and XRCC1 (Gln/Gln)-ERCC2 (Lys/Gln) (OR = 0.36, 95% CI = 0.11-1.17) and reduced risk of ESQCC in the North Indian population. These observations suggest that the Gln/Gln genotype of XRCC1 might play an important role in DNA repair in ESQCC. PMID:17556064

Sobti, Ranbir Chander; Singh, Jagmohan; Kaur, Pushpinder; Pachouri, Suparna S; Siddiqui, Ehtesham A; Bindra, Harnish Singh

2007-06-01

377

Adolescents' Attitudes Toward Antimarijuana Ads, Usage Intentions, and Actual Marijuana Usage.  

PubMed

The association of adolescents' appraisals of the antimarijuana TV ads used in the National Youth Antidrug Media Campaign with future marijuana use was investigated. The 12- to 18-year-old respondents (N = 2,993) were first classified as users, resolute nonusers, or vulnerable nonusers (Crano, Siegel, Alvaro, Lac, & Hemovich, 2008). Usage status and the covariates of gender, age, and attitudes toward marijuana were used to predict attitudes toward the ads (Aad) in the first phase of a multilevel linear analysis. All covariates were significantly associated with Aad, as was usage status: Resolute nonusers evaluated the ads significantly more positively than vulnerable nonusers and users (all ps < .001), who did not differ. In the second phase, the covariates along with Aad and respondents' usage status predicted intentions and actual usage 1 year after initial measurement. The lagged analysis disclosed negative associations between Aad and usage intentions and between Aad and actual marijuana use (both ps < .05); however, this association held only for users (p < .01), not vulnerable or resolute nonusers. Users who reported more positive attitudes toward the ads were less likely to report intention to use marijuana and to continue marijuana use at 1-year follow-up. These findings may inform designers of persuasion-based prevention campaigns, guiding preimplementation efforts in the design of ads that targeted groups find appealing and thus, influential. (PsycINFO Database Record (c) 2013 APA, all rights reserved). PMID:23528197

Alvaro, Eusebio M; Crano, William D; Siegel, Jason T; Hohman, Zachary; Johnson, Ian; Nakawaki, Brandon

2013-03-25

378

P53 codon 72 Arg/Pro polymorphism and glioma risk: an updated meta-analysis.  

PubMed

P53 codon 72 Arg/Pro is a C/G variation upstream of the p53 gene on human chromosome 17p13. Many case-control studies have investigated the association between p53 codon 72 Arg/Pro polymorphism and glioma risk but provided inconsistent findings. To better understand the pathogenesis of glioma, we performed the current meta-analysis by pooling data from all available individual studies. According to the inclusion criteria, ten independent publications with 11 case-control studies were included into this meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the effect of p53 codon 72 Arg/Pro variant on the development of glioma. Overall, no appreciable correlation was observed among the total studies in all gene models (ORPro allele vs. Arg allele?=?1.04, 95 % CI?=?0.90-1.20, P OR?=?0.581; ORPro/Pro vs. Arg/Arg?=?0.95, 95 % CI?=?0.80-1.14, P OR?=?0.614; ORPro/Arg vs. Arg/Arg?=?1.01, 95 % CI?=?0.79-1.29, P OR?=?0.993; ORPro/Arg + Pro/Pro vs. Arg/Arg?=?1.03, 95 % CI?=?0.82-1.29, P OR?=?0.799; ORPro/Pro vs. Arg/Arg + Pro/Arg?=?1.02, 95 % CI?=?0.86-1.22, P OR?=?0.785). In stratified analyses by ethnicity, source of controls, and glioma subtypes, the p53 codon 72 Arg/Pro polymorphism did not alter the risk for glioma in population-based, hospital-based, astrocytoma, and oligodendroglioma studies among Caucasian. Interestingly, the Pro/Pro genotype seemed to be negatively associated with the glioma risk among patients with glioblastoma (ORPro/Pro vs. Arg/Arg?=?0.68, 95 % CI?=?0.48-0.95, P OR?=?0.026). Our study suggests that the polymorphism of p53 codon 72 Arg/Pro may play a protective role in the development of glioblastoma. The relationship of p53 codon 72 Arg/Pro polymorphism with the susceptibility to glioma needs further estimation by more individual studies with high quality across ethnicities. PMID:23860773

He, Fang; Xia, Yi; Liu, Huafeng; Li, Jin; Wang, Chao

2013-07-17

379

Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count  

PubMed Central

Background The human APOBEC3G (A3G) protein activity is associated with innate immunity against HIV-1 by inducing high rates of guanosines to adenosines (G-to-A) mutations (viz., hypermutation) in the viral DNA. If hypermutation is not enough to disrupt the reading frames of viral genes, it may likely increase the HIV-1 diversity. To counteract host innate immunity HIV-1 encodes the Vif protein that binds A3G protein and form complexes to be degraded by cellular proteolysis. Methods Here we studied the pattern of substitutions in the vif gene and its association with clinical status of HIV-1 infected individuals. To perform the study, unique vif gene sequences were generated from 400 antiretroviral-naïve individuals. Results The codon pairs: 78–154, 85–154, 101–157, 105–157, and 105–176 of vif gene were associated with CD4+ T cell count lower than 500 cells per mm3. Some of these codons were located in the 81LGQGVSIEW89 region and within the BC-Box. We also identified codons under positive selection clustered in the N-terminal region of Vif protein, between 21WKSLVK26 and 40YRHHY44 regions (i.e., 31, 33, 37, 39), within the BC-Box (i.e., 155, 159) and the Cullin5-Box (i.e., 168) of vif gene. All these regions are involved in the Vif-induced degradation of A3G/F complexes and the N-terminal of Vif protein binds to viral and cellular RNA. Conclusions Adaptive evolution of vif gene was mostly to optimize viral RNA binding and A3G/F recognition. Additionally, since there is not a fully resolved structure of the Vif protein, codon pairs associated with CD4+ T cell count may elucidate key regions that interact with host cell factors. Here we identified and discriminated codons under positive selection and codons under functional constraint in the vif gene of HIV-1.

2013-01-01

380

Frequency of Humidifier and Humidifier Disinfectant Usage in Gyeonggi Provine  

PubMed Central

Objectives This study is a cross-sectional study to investigate the frequency of humidifier and humidifier disinfectant usage in the general population. Methods A questionnaire was applied to 94 subjects (46 male, 48 female) from the general population of Gyeonggi Province. The questionnaire consisted of 3 scales (general characteristics, 5 items about humidifier usage, 5 items about humidifier disinfectant usage). Results Thirty-five (37.2%) of the 94 subjects use a humidifier and humidifier disinfectant usage was found to be 18.1%. The frequency of humidifier usage is 4.8 times per a week and the humidifier disinfectant usage is 2.4 times per a week. Humidifier usage rate was highest in January. and then tended to rise gradually from October. Conclusions Although this study population was not representative, we can say that approximately 50 percent of the humidifier users use a humidifier disinfectant and the trend of using a humidifier has shown seasonality.

Park, Young Joon

2012-01-01

381

Rapid communication Overcoming codon bias: A method for high-level overexpression of Plasmodium and other AT-rich parasite genes in Escherichia coli  

Microsoft Academic Search

Parasite genes often use codons which are rarely used in the highly expressed genes of Escherichia coli, possibly resulting in translational stalling and lower yields of recombinant protein. We have constructed the ''RIG'' plasmid to overcome the potential codon-bias problem seen in Plasmodium genes. RIG contains the genes that encode three tRNAs (Arg, Ile, Gly), which recognise rare codons found

Arthur M. Baca; Wim G. J. Hol

382

Quantitative codon optimisation of DNA libraries encoding sub-random peptides: design and characterisation of a novel library encoding transmembrane domain peptides  

Microsoft Academic Search

Codons for amino acids sharing similar chemical properties seem to cluster on the genetic codon table. Such a geographical distribution of the codons was exploited to create chemically synthe- sised DNA that encodes peptide libraries containing only a subset of the 20 natural amino acids. The frequency of each amino acid in the subset was further optimised by quantitatively manipulating

Ola Larsson; Dorit Thormeyer; Arian Asinger; Bjorn Wihlen; Claes Wahlestedt; Zicai Liang

2002-01-01

383

Specific Mutations in KRAS Codons 12 and 13, and Patient Prognosis in 1075 BRAF-wild-type Colorectal Cancers  

PubMed Central

Purpose To assess prognostic roles of various KRAS oncogene mutations in colorectal cancer, BRAF mutation status must be controlled for because BRAF mutation is associated with poor prognosis, and almost all BRAF mutants are present among KRAS-wild-type tumors. Taking into account experimental data supporting a greater oncogenic effect of codon 12 mutations compared to codon 13 mutations, we hypothesized that KRAS codon 12 mutated colorectal cancers might behave more aggressively than KRAS-wild-type tumors and codon 13 mutants. Experimental design Utilizing molecular pathological epidemiology database of 1261 rectal and colon cancers, we examined clinical outcome and tumor biomarkers of KRAS codon 12 and 13 mutations in 1075 BRAF-wild-type cancers (i.e., controlling for BRAF status). Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for potential confounders, including stage, PIK3CA mutations, microsatellite instability, CpG island methylator phenotype, and LINE-1 methylation. Results Compared to patients with KRAS-wild-type/BRAF-wild-type cancers (N=635), those with KRAS codon 12 mutations (N=332) experienced significantly higher colorectal cancer-specific mortality [log-rank P=0.0001; multivariate HR=1.30; 95% confidence interval (CI), 1.02–1.67; P=0.037], whereas KRAS codon 13 mutated cases (N=108) were not significantly associated with prognosis. Among the seven most common KRAS mutations, c.35G>T (p.G12V; N=93) was associated with significantly higher colorectal cancer-specific mortality (log-rank P=0.0007; multivariate HR=2.00, 95% CI, 1.38–2.90, P=0.0003) compared to KRAS-wild-type/BRAF-wild-type cases. Conclusions KRAS codon 12 mutations (in particular, c.35G>T), but not codon 13 mutations, are associated with inferior survival in BRAF-wild-type colorectal cancer. Our data highlight the importance of accurate molecular characterization in colorectal cancer.

Imamura, Yu; Morikawa, Teppei; Liao, Xiaoyun; Lochhead, Paul; Kuchiba, Aya; Yamauchi, Mai; Qian, Zhi Rong; Nishihara, Reiko; Meyerhardt, Jeffrey A.; Haigis, Kevin M.; Fuchs, Charles S.; Ogino, Shuji

2013-01-01

384

The human mitochondrial tRNAMet: Structure/function relationship of a unique modification in the decoding of unconventional codons  

PubMed Central

Human mitochondrial mRNAs utilize the universal AUG and the unconventional isoleucine AUA codons for methionine. In contrast to translation in the cytoplasm, human mitochondria use one tRNA, hmtRNAMetCAU, to read AUG and AUA codons at both the peptidyl- (P-), and aminoacyl-(A-) sites of the ribosome. The hmtRNAMetCAU has a unique post-transcriptional modification, 5-formylcytidine, at the wobble position 34 (f5C34), and a cytidine substituting for the invariant uridine at position 33 of the canonical “U-turn” in tRNAs. The structure of the tRNA's anticodon stem and loop domain (hmtASLMetCAU), determined by NMR restrained molecular modeling, revealed how the f5C34 modification facilitates the decoding of AUA at the P- and A-sites. The f5C34 defined a reduced conformational space for the nucleoside, in what appears to have restricted the conformational dynamics of the anticodon bases of the modified hmtASLMetCAU. The hmtASLMetCAU exhibited a “C-turn” conformation that has some characteristics of the U-turn motif. Codon binding studies with both E. coli and bovine mitochondrial ribosomes revealed that the f5C34 facilitates AUA binding in the A-site and suggested that the modification favorably alters the ASL's binding kinetics. Mitochondrial translation by many organisms including humans sometimes initiates with the universal isoleucine codons AUU and AUC. The f5C34 enabled P-site codon binding to these normally isoleucine codons. Thus, the physicochemical properties of this one modification, f5C34, expand codon recognition from the traditional AUG to the non-traditional, synonymous codons AUU and AUC as well as AUA, in the reassignment of universal codons in the mitochondria.

Bilbille, Yann; Gustilo, Estella M.; Harris, Kimberly A.; Jones, Christie N.; Lusic, Hrvoje; Kaiser, Robert J.; Delaney, Michael O.; Spremulli, Linda L.; Deiters, Alexander; Agris, Paul F.

2011-01-01

385

An assessment of worldwide supercomputer usage  

SciTech Connect

This report provides a comparative study of advanced supercomputing usage in Japan and the United States as of Spring 1994. It is based on the findings of a group of US scientists whose careers have centered on programming, evaluating, and designing high-performance supercomputers for over ten years. The report is a follow-on to an assessment of supercomputing technology in Europe and Japan that was published in 1993. Whereas the previous study focused on supercomputer manufacturing capabilities, the primary focus of the current work was to compare where and how supercomputers are used. Research for this report was conducted through both literature studies and field research in Japan.

Wasserman, H.J.; Simmons, M.L.; Hayes, A.H.

1995-01-01

386

Clinical significance of HIV-1 coreceptor usage  

PubMed Central

The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage.

2011-01-01

387

Degradation of mRNAs that lack a stop codon: A decade of nonstop progress  

PubMed Central

Nonstop decay is the mechanism of identifying and disposing aberrant transcripts that lack in-frame stop codons. It is hypothesized that these transcripts are identified during translation when the ribosome arrives at the 3? end of the mRNA and stalls. Presumably the ribosome stalling recruits additional cofactors, Ski7 and the exosome complex. The exosome degrades the transcript using either one of is ribonucleolytic activities and the ribosome and the peptide are both released. Additional precautionary measures by the nonstop decay pathway may include translational repression of the nonstop transcript after translation, and proteolysis of the released peptide by the proteasome. This surveillance mechanism protects the cells from potentially harmful truncated proteins, but it may also be involved in mediating critical cellular functions of transcripts that are prone to stop codon read-through. Important advances have been made in the past decade as we learn that nonstop decay may have implications in human disease.

Klauer, A. Alejandra; van Hoof, Ambro

2013-01-01

388

A POPULATION-SPECIFIC HTR2B STOP CODON PREDISPOSES TO SEVERE IMPULSIVITY  

PubMed Central

SUMMARY Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behavior. The complex origins of impulsivity hinder identification of the genes influencing both it and diseases with which it is associated. We performed exon-centric sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B that is common (MAF >1%) but exclusive to Finns was identified. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon that was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviors in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioral phenotypes using founder populations, and suggests a role for HTR2B in impulsivity.

Bevilacqua, Laura; Doly, Stephane; Kaprio, Jaakko; Yuan, Qiaoping; Tikkanen, Roope; Paunio, Tiina; Zhou, Zhifeng; Wedenoja, Juho; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud; Hodgkinson, Colin A.; Dell'Osso, Liliana; Suvisaari, Jaana; Coccaro, Emil; Rose, Richard J; Peltonen, Leena; Virkkunen, Matti; Goldman, David

2011-01-01

389

Lack of IRS-1 codon 513 and 972 polymorphism in Pima Indians  

SciTech Connect

Insulin receptor substrate-1 (IRS-1), a 1242 amino acid protein, an endogenous substrate for the insulin receptor tyrosine kinase, mediates many or all of the metabolic actions of insulin. Recently, polymorphism at codons 513 and 972 of the IRS-1 gene resulting in 2 amino acid substitutions that were associated with type II diabetes were found in a Caucasian population. Using allele specific oligonucleotide (ASO) hybridization, we screened 242 diabetic and 190 nondiabetic Pima Indians, a population with a very high prevalence of type II diabetes. Neither of the two mutations was present in either diabetic or nondiabetic subjects. We conclude that polymorphism at codons 513 and 972 of the IRS-1 gene observed in certain Caucasian populations is very rare or absent in Pima Indians. 20 refs., 2 figs., 1 tab.

Celi, F.S.; Silver, K.; Walston, J. [and others

1995-09-01

390

Translation efficiency is determined by both codon bias and folding energy.  

PubMed

Synonymous mutations do not alter the protein produced yet can have a significant effect on protein levels. The mechanisms by which this effect is achieved are controversial; although some previous studies have suggested that codon bias is the most important determinant of translation efficiency, a recent study suggested that mRNA folding at the beginning of genes is the dominant factor via its effect on translation initiation. Using the Escherichia coli and Saccharomyces cerevisiae transcriptomes, we conducted a genome-scale study aiming at dissecting the determinants of translation efficiency. There is a significant association between codon bias and translation efficiency across all endogenous genes in E. coli and S. cerevisiae but no association between folding energy and translation efficiency, demonstrating the role of codon bias as an important determinant of translation efficiency. However, folding energy does modulate the strength of association between codon bias and translation efficiency, which is maximized at very weak mRNA folding (i.e., high folding energy) levels. We find a strong correlation between the genomic profiles of ribosomal density and genomic profiles of folding energy across mRNA, suggesting that lower folding energies slow down the ribosomes and decrease translation efficiency. Accordingly, we find that selection forces act near uniformly to decrease the folding energy at the beginning of genes. In summary, these findings testify that in endogenous genes, folding energy affects translation efficiency in a global manner that is not related to the expression levels of individual genes, and thus cannot be detected by correlation with their expression levels. PMID:20133581

Tuller, Tamir; Waldman, Yedael Y; Kupiec, Martin; Ruppin, Eytan

2010-02-02

391

Translation efficiency is determined by both codon bias and folding energy  

PubMed Central

Synonymous mutations do not alter the protein produced yet can have a significant effect on protein levels. The mechanisms by which this effect is achieved are controversial; although some previous studies have suggested that codon bias is the most important determinant of translation efficiency, a recent study suggested that mRNA folding at the beginning of genes is the dominant factor via its effect on translation initiation. Using the Escherichia coli and Saccharomyces cerevisiae transcriptomes, we conducted a genome-scale study aiming at dissecting the determinants of translation efficiency. There is a significant association between codon bias and translation efficiency across all endogenous genes in E. coli and S. cerevisiae but no association between folding energy and translation efficiency, demonstrating the role of codon bias as an important determinant of translation efficiency. However, folding energy does modulate the strength of association between codon bias and translation efficiency, which is maximized at very weak mRNA folding (i.e., high folding energy) levels. We find a strong correlation between the genomic profiles of ribosomal density and genomic profiles of folding energy across mRNA, suggesting that lower folding energies slow down the ribosomes and decrease translation efficiency. Accordingly, we find that selection forces act near uniformly to decrease the folding energy at the beginning of genes. In summary, these findings testify that in endogenous genes, folding energy affects translation efficiency in a global manner that is not related to the expression levels of individual genes, and thus cannot be detected by correlation with their expression levels.

Tuller, Tamir; Waldman, Yedael Y.; Kupiec, Martin; Ruppin, Eytan

2010-01-01

392

Mutant 16S Ribosomal RNA: A Codon-Specific Translational Suppressor  

Microsoft Academic Search

We have isolated an unusual codon-specific translational suppressor in Escherichia coli. The suppressor resulted from a spontaneous mutation in a chromosomal gene during a selection for suppressors of the auxotrophic nonsense mutation trpA(UGA211). The suppressor allows readthrough of UGA mutations at two positions in trpA and at two sites in bacteriophage T4. It does not, however, suppress amber (UAG) or

Emanuel J. Murgola; Kathryn A. Hijazi; H. Ulrich Goringer; Albert E. Dahlberg

1988-01-01

393

When nonsense makes sense and vice versa: Noncanonical decoding events at stop codons in eukaryotes  

Microsoft Academic Search

Regulation of protein synthesis at the level of translation termination is a relatively underexplored, but rapidly expanding\\u000a field. Recent advances in elucidating the mechanism of translation termination are helping to understand noncanonical events\\u000a associated with translation termination. These “recording” events include read-through of stop codons, insertion of unusual\\u000a amino acids such as selenocysteine, and production of several polypeptides from one

V. A. Doronina; J. D. Brown

2006-01-01

394

?- l-Iduronidase Premature Stop Codons and Potential Read-Through in Mucopolysaccharidosis Type I Patients  

Microsoft Academic Search

?-l-Iduronidase is a glycosyl hydrolase involved in the sequential degradation of the glycosaminoglycans heparan sulphate and dermatan sulphate. A deficiency in ?-l-iduronidase results in the lysosomal accumulation and urinary secretion of partially degraded glycosaminoglycans and is the cause of the lysosomal storage disorder mucopolysaccharidosis type I (MPS I; Hurler and Scheie syndromes; McKusick 25280). The premature stop codons Q70X and

Leanne K Hein; Michael Bawden; Vivienne J Muller; David Sillence; John J Hopwood; Doug A Brooks

2004-01-01

395

Ethnic variation in the HER2 codon 655 genetic polymorphism previously associated with breast cancer  

Microsoft Academic Search

HER-2, a protooncogene located on chromosome 17q21, encodes a transmembrane glycoprotein (p185) with tyrosine kinase activity.\\u000a Alterations of the HER-2 gene have been implicated in the carcinogenesis and prognosis of breast cancer and other solid tumors. It is also a cancer-therapeutic\\u000a target for antibody-based therapy against the HER-2 protein. A single-nucleotide polymorphism (SNP) at codon 655, resulting in a G-to-A

Margaret-Mary Ameyaw; Mohammed Tayeb; Nadia Thornton; Gbolahan Folayan; Mohammed Tariq; Abeer Mobarek; David A. Price Evans; David Ofori-Adjei; Howard L. McLeod

2002-01-01

396

Glutathione Peroxidase Codon 198 Polymorphism Variant Increases Lung Cancer Risk1  

Microsoft Academic Search

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-depen- dent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the a-Tocopherol, b-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymor- phism at codon 198 of hGPX1 and lung cancer risk.

Duminda Ratnasinghe; Joseph A. Tangrea; Mark R. Andersen; Michael J. Barrett; Jarmo Virtamo; Philip R. Taylor; Demetrius Albanes

397

GTP Hydrolysis by eRF3 Facilitates Stop Codon Decoding during Eukaryotic Translation Termination  

Microsoft Academic Search

Translation termination in eukaryotes is mediated by two release factors, eRF1 and eRF3. eRF1 recognizes each of the three stop codons (UAG, UAA, and UGA) and facilitates release of the nascent polypeptide chain. eRF3 is a GTPase that stimulates the translation termination process by a poorly characterized mechanism. In this study, we examined the functional importance of GTP hydrolysis by

Joe Salas-Marco; David M. Bedwell

2004-01-01

398

Translational Polarity of a Mutation in the Initiator AUG Codon of the X cl Gene  

Microsoft Academic Search

A P-cI-lac2 fusion inserted into the 62 region of bacteriophage X was used to isolate mutations affecting expression of both the X cI gene and the lac2 gene. One such mutation, a change in the CI initiator codon from AUG to AUA, reduces immunity of a X prophage to superinfection, and causes a 60-70% reduction in &galactosidase synthesis, even when

Gary N. Gussin; Susan Brown; Karen Matz

1987-01-01

399

TP53 codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis  

Microsoft Academic Search

Colorectal cancer constitutes a significant proportion of the global burden of cancer morbidity and mortality. A number of\\u000a studies have been conducted to explore whether TP53 codon 72 polymorphism is associated with colorectal cancer susceptibility. However, controversial results were obtained.\\u000a In order to derive a more precise estimation of the relationship, we systematically searched Medline, Google scholar, and\\u000a Ovid database

Jing-Jun WangYuan; Yuan Zheng; Liang Sun; Li Wang; Peng-Bo Yu; Jian-Hua Dong; Lei Zhang; Jing Xu; Wei Shi; Yu-Chun Ren

400

Aminoglycoside suppression at UAG, UAA and UGA codons in Escherichia coli and human tissue culture cells  

Microsoft Academic Search

Summary  We have compared the suppression of nonsense mutations by aminoglycoside antibiotics inEscherichia coli and in human 293 cells. Six nonsense alleles of the chloramphenicol acetyl transferase (cat) gene, in the vector pRSVcat, were suppressed by growth in G418 and paromomycin. Readthrough at UAG, UAA and UGA codons was monitored with enzyme assays\\u000a for chloramphenicol acetyl transferase (CAT), in stably transformed

Robin Martin; Anne E. Mogg; Louise A. Heywood; Lars Nitschke; Julian F. Burke

1989-01-01

401

Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia  

Microsoft Academic Search

AimsOphthalmic pterygium is a potentially vision-threatening lesion of unknown etiology, related to an exposure to solar light. Mutations to the ras genes are frequently observed in lesions related to an exposure to solar light. The present study aims at screening pterygia for mutations at codons 12 and 13 of the ras genes.MethodsIn all, 50 pterygia were examined, together with respective

E T Detorakis; A Zafiropoulos; D A Arvanitis; D A Spandidos

2005-01-01

402

Better Living Through Metadata: Examining Archive Usage  

NASA Astrophysics Data System (ADS)

The primary purpose of an observatory's archive is to provide access to the data through various interfaces. User interactions with the archive are recorded in server logs, which can be used to answer basic questions like: Who has downloaded dataset X? When did she do this? Which tools did she use? The answers to questions like these fill in patterns of data access (e.g., how many times dataset X has been downloaded in the past three years). Analysis of server logs provides metrics of archive usage and provides feedback on interface use which can be used to guide future interface development. The Chandra X-ray Observatory is fortunate in that a database to track data access and downloads has been continuously recording such transactions for years; however, it is overdue for an update. We will detail changes we hope to effect and the differences the changes may make to our usage metadata picture. We plan to gather more information about the geographic location of users without compromising privacy; create improved archive statistics; and track and assess the impact of web “crawlers” and other scripted access methods on the archive. With the improvements to our download tracking we hope to gain a better understanding of the dissemination of Chandra's data; how effectively it is being done; and perhaps discover ideas for new services.

Becker, G.; Winkelman, S.; Rots, A.

2013-10-01

403

Recognition of the amber UAG stop codon by release factor RF1  

SciTech Connect

We report the crystal structure of a termination complex containing release factor RF1 bound to the 70S ribosome in response to an amber (UAG) codon at 3.6-{angstrom} resolution. The amber codon is recognized in the 30S subunit-decoding centre directly by conserved elements of domain 2 of RF1, including T186 of the PVT motif. Together with earlier structures, the mechanisms of recognition of all three stop codons by release factors RF1 and RF2 can now be described. Our structure confirms that the backbone amide of Q230 of the universally conserved GGQ motif is positioned to contribute directly to the catalysis of the peptidyl-tRNA hydrolysis reaction through stabilization of the leaving group and/or transition state. We also observe synthetic-negative interactions between mutations in the switch loop of RF1 and in helix 69 of 23S rRNA, revealing that these structural features interact functionally in the termination process. These findings are consistent with our proposal that structural rearrangements of RF1 and RF2 are critical to accurate translation termination.

Korostelev, Andrei; Zhu, Jianyu; Asahara, Haruichi; Noller, Harry F. (UCSC)

2010-08-23

404

A method for multi-codon scanning mutagenesis of proteins based on asymmetric transposons  

PubMed Central

Random mutagenesis followed by selection or screening is a commonly used strategy to improve protein function. Despite many available methods for random mutagenesis, nearly all generate mutations at the nucleotide level. An ideal mutagenesis method would allow for the generation of ‘codon mutations’ to change protein sequence with defined or mixed amino acids of choice. Herein we report a method that allows for mutations of one, two or three consecutive codons. Key to this method is the development of a Mu transposon variant with asymmetric terminal sequences. As a demonstration of the method, we performed multi-codon scanning on the gene encoding superfolder GFP (sfGFP). Characterization of 50 randomly chosen clones from each library showed that more than 40% of the mutants in these three libraries contained seamless, in-frame mutations with low site preference. By screening only 500 colonies from each library, we successfully identified several spectra-shift mutations, including a S205D variant that was found to bear a single excitation peak in the UV region.

Liu, Jia; Cropp, T.Ashton

2012-01-01

405

Codon conservation in the influenza A virus genome defines RNA packaging signals.  

PubMed

Genome segmentation facilitates reassortment and rapid evolution of influenza A virus. However, segmentation complicates particle assembly as virions must contain all eight vRNA species to be infectious. Specific packaging signals exist that extend into the coding regions of most if not all segments, but these RNA motifs are poorly defined. We measured codon variability in a large dataset of sequences to identify areas of low nucleotide sequence variation independent of amino acid conservation in each segment. Most clusters of codons showing very little synonymous variation were located at segment termini, consistent with previous experimental data mapping packaging signals. Certain internal regions of conservation, most notably in the PA gene, may however signify previously unidentified functions in the virus genome. To experimentally test the bioinformatics analysis, we introduced synonymous mutations into conserved codons within known packaging signals and measured incorporation of the mutant segment into virus particles. Surprisingly, in most cases, single nucleotide changes dramatically reduced segment packaging. Thus our analysis identifies cis-acting sequences in the influenza virus genome at the nucleotide level. Furthermore, we propose that strain-specific differences exist in certain packaging signals, most notably the haemagglutinin gene; this finding has major implications for the evolution of pandemic viruses. PMID:17332012

Gog, Julia R; Afonso, Emmanuel Dos Santos; Dalton, Rosa M; Leclercq, India; Tiley, Laurence; Elton, Debra; von Kirchbach, Johann C; Naffakh, Nadia; Escriou, Nicolas; Digard, Paul

2007-03-01

406

p53 codon 72 polymorphism and coronary artery disease: Evidence of interaction with ACP1  

PubMed Central

Summary Background Common biological features between cancer and atherosclerosis suggest possible association of p53 with atherosclerotic diseases, but data on such a relationship are controversial, suggesting interactions with other variables. Acid phosphatase locus 1 (ACP1) is a polymorphic gene that controls the synthesis of an enzyme involved in important metabolic functions. Since ACP1 is associated with coronary artery disease (CAD), we searched for possible interactions between this enzyme and p53 codon 72 polymorphism with regard to their effects on susceptibility to CAD. Material/Methods The study included 381 patients admitted to the hospital for cardiovascular disease (232 patients with CAD and 149 with other cardiovascular problems) and 97 healthy newborns. Results The proportion of subjects carrying the *Pro allele of p53 codon 72 and the high activity *B*C genotype of ACP1 is higher in CAD (10.3%) than in non-CAD patients (2.0%) and in healthy newborns (6.2%). Conclusions The data suggest an interaction between p53 codon 72 and ACP1 wherein a positive effect of the p53 *Pro allele on susceptibility to CAD occurs, but only in the presence of the ACP1 genotype characterized by high enzymatic activity.

Gloria-Bottini, Fulvia; Banci, Maria; Saccucci, Patrizia; Neri, Anna; Bottini, Egidio; Magrini, Andrea

2012-01-01

407

Codon Optimization Significantly Improves the Expression Level of a Keratinase Gene in Pichia pastoris  

PubMed Central

The main keratinase (kerA) gene from the Bacillus licheniformis S90 was optimized by two codon optimization strategies and expressed in Pichia pastoris in order to improve the enzyme production compared to the preparations with the native kerA gene. The results showed that the corresponding mutations (synonymous codons) according to the codon bias in Pichia pastoris were successfully introduced into keratinase gene. The highest keratinase activity produced by P. pastoris pPICZ?A-kerAwt, pPICZ?A-kerAopti1 and pPICZ?A-kerAopti2 was 195 U/ml, 324 U/ml and 293 U/ml respectively. In addition, there was no significant difference in biomass concentration, target gene copy numbers and relative mRNA expression levels of every positive strain. The molecular weight of keratinase secreted by recombinant P. pastori was approx. 39 kDa. It was optimally active at pH 7.5 and 50°C. The recombinant keratinase could efficiently degrade both ?-keratin (keratin azure) and ?-keratin (chicken feather meal). These properties make the P. pastoris pPICZ?A-kerAopti1 a suitable candidate for industrial production of keratinases.

Hu, Hong; Gao, Jie; He, Jun; Yu, Bing; Zheng, Ping; Huang, Zhiqing; Mao, Xiangbing; Yu, Jie; Han, Guoquan; Chen, Daiwen

2013-01-01

408

Codon optimization significantly improves the expression level of a keratinase gene in Pichia pastoris.  

PubMed

The main keratinase (kerA) gene from the Bacillus licheniformis S90 was optimized by two codon optimization strategies and expressed in Pichia pastoris in order to improve the enzyme production compared to the preparations with the native kerA gene. The results showed that the corresponding mutations (synonymous codons) according to the codon bias in Pichia pastoris were successfully introduced into keratinase gene. The highest keratinase activity produced by P. pastoris pPICZ?A-kerAwt, pPICZ?A-kerAopti1 and pPICZ?A-kerAopti2 was 195 U/ml, 324 U/ml and 293 U/ml respectively. In addition, there was no significant difference in biomass concentration, target gene copy numbers and relative mRNA expression levels of every positive strain. The molecular weight of keratinase secreted by recombinant P. pastori was approx. 39 kDa. It was optimally active at pH 7.5 and 50°C. The recombinant keratinase could efficiently degrade both ?-keratin (keratin azure) and ?-keratin (chicken feather meal). These properties make the P. pastoris pPICZ?A-kerAopti1 a suitable candidate for industrial production of keratinases. PMID:23472192

Hu, Hong; Gao, Jie; He, Jun; Yu, Bing; Zheng, Ping; Huang, Zhiqing; Mao, Xiangbing; Yu, Jie; Han, Guoquan; Chen, Daiwen

2013-03-05

409

A method for multi-codon scanning mutagenesis of proteins based on asymmetric transposons.  

PubMed

Random mutagenesis followed by selection or screening is a commonly used strategy to improve protein function. Despite many available methods for random mutagenesis, nearly all generate mutations at the nucleotide level. An ideal mutagenesis method would allow for the generation of 'codon mutations' to change protein sequence with defined or mixed amino acids of choice. Herein we report a method that allows for mutations of one, two or three consecutive codons. Key to this method is the development of a Mu transposon variant with asymmetric terminal sequences. As a demonstration of the method, we performed multi-codon scanning on the gene encoding superfolder GFP (sfGFP). Characterization of 50 randomly chosen clones from each library showed that more than 40% of the mutants in these three libraries contained seamless, in-frame mutations with low site preference. By screening only 500 colonies from each library, we successfully identified several spectra-shift mutations, including a S205D variant that was found to bear a single excitation peak in the UV region. PMID:22184456

Liu, Jia; Cropp, T Ashton

2011-12-18

410

Widespread Polymorphism in the Positions of Stop Codons in Drosophila melanogaster  

PubMed Central

The mechanisms underlying evolutionary changes in protein length are poorly understood. Protein domains are lost and gained between species and must have arisen first as within-species polymorphisms. Here, we use Drosophila melanogaster population genomic data combined with between species divergence information to understand the evolutionary forces that generate and maintain polymorphisms causing changes in protein length in D. melanogaster. Specifically, we looked for protein length variations resulting from premature termination codons (PTCs) and stop codon losses (SCLs). We discovered that 438 genes contained polymorphisms resulting in truncation of the translated region (PTCs) and 119 genes contained polymorphisms predicted to lengthen the translated region (SCLs). Stop codon polymorphisms (SCPs) (especially PTCs) appear to be more deleterious than other polymorphisms, including protein amino acid changes. Genes harboring SCPs are in general less selectively constrained, more narrowly expressed, and enriched for dispensable biological functions. However, we also observed exceptional cases such as genes that have multiple independent SCPs, alleles that are shared between D. melanogaster and Drosophila simulans, and high-frequency alleles that cause extreme changes in gene length. SCPs likely have an important role in the evolution of these genes.

Lee, Yuh Chwen G.; Reinhardt, Josephine A.

2012-01-01

411

Recognition of the amber UAG stop codon by release factor RF1  

PubMed Central

We report the crystal structure of a termination complex containing release factor RF1 bound to the 70S ribosome in response to an amber (UAG) codon at 3.6-Å resolution. The amber codon is recognized in the 30S subunit-decoding centre directly by conserved elements of domain 2 of RF1, including T186 of the PVT motif. Together with earlier structures, the mechanisms of recognition of all three stop codons by release factors RF1 and RF2 can now be described. Our structure confirms that the backbone amide of Q230 of the universally conserved GGQ motif is positioned to contribute directly to the catalysis of the peptidyl-tRNA hydrolysis reaction through stabilization of the leaving group and/or transition state. We also observe synthetic-negative interactions between mutations in the switch loop of RF1 and in helix 69 of 23S rRNA, revealing that these structural features interact functionally in the termination process. These findings are consistent with our proposal that structural rearrangements of RF1 and RF2 are critical to accurate translation termination.

Korostelev, Andrei; Zhu, Jianyu; Asahara, Haruichi; Noller, Harry F

2010-01-01

412

The rare codon 24 (T>A) (beta+) mutation in association with the common codon 39 (C> T) (beta0) mutation causes transfusion-dependent beta-thalassemia in a Moroccan patient.  

PubMed

We present the rare codon 24 (T > A) (beta(+)) mutation causing transfusion-dependent beta-thalassemia (beta-thal) in combination with the common codon 39 (C > T) (beta(0)) defect in a Moroccan boy. We report the characterization of the mutation, phenotype, haplotype and possible origin of the first case in Morocco and discuss the significance of this genotype combination with a beta(0) defect. PMID:19373592

Agouti, Imane; Bennani, Mohcine; Levy, Nicolas; Giordano, Piero; Badens, Catherine

2009-01-01

413

Near-cognate suppression of amber, opal and quadruplet codons competes with aminoacyl-tRNAPyl for genetic code expansion.  

PubMed

Over 300 amino acids are found in proteins in nature, yet typically only 20 are genetically encoded. Reassigning stop codons and use of quadruplet codons emerged as the main avenues for genetically encoding non-canonical amino acids (NCAAs). Canonical aminoacyl-tRNAs with near-cognate anticodons also read these codons to some extent. This background suppression leads to 'statistical protein' that contains some natural amino acid(s) at a site intended for NCAA. We characterize near-cognate suppression of amber, opal and a quadruplet codon in common Escherichia coli laboratory strains and find that the PylRS/tRNA(Pyl) orthogonal pair cannot completely outcompete contamination by natural amino acids. PMID:23036644

O'Donoghue, Patrick; Prat, Laure; Heinemann, Ilka U; Ling, Jiqiang; Odoi, Keturah; Liu, Wenshe R; Söll, Dieter

2012-10-01

414

Allelic frequency and genotypes of prion protein at codon 136 and 171 in Iranian Ghezel sheep breeds  

PubMed Central

PrP genotypes at codons 136 and 171 in 120 Iranian Ghezel sheep breeds were studied using allele-specific PCR amplification and compared with the well-known sheep breeds in North America, the United States and Europe. The frequency of V allele and VV genotype at codon 136 of Ghezel sheep breed was significantly lower than AA and AV. At codon 171, the frequency of allele H was significantly lower than Q and R. Despite the similarities of PrP genotypes at codons 136 and 171 between Iranian Ghezel sheep breeds and some of the studied breeds, significant differences were found with others. Planning of effective breeding control and successful eradication of susceptible genotypes in Iranian Ghezel sheep breeds will not be possible unless the susceptibility of various genotypes in Ghezel sheep breeds to natural or experimental scrapie has been elucidated.

Zadeh, Reza Ashrafi; Omrani, Mir Davood; Ramezani, Fatemeh; Amniattalab, Amir

2011-01-01

415

The Bacterial Toxin RelE Displays Codon-Specific Cleavage of mRNAs in the Ribosomal A Site  

Microsoft Academic Search

The Escherichia coli relBE operon encodes a toxin-antitoxin pair, RelE-RelB. RelB can reverse inhibition of protein synthesis by RelE in vivo. We have found that although RelE does not degrade free RNA, it cleaves mRNA in the ribosomal A site with high codon specificity. Among stop codons UAG is cleaved with fast, UAA intermediate and UGA slow rate, while UCG

Kim Pedersen; Andrey V. Zavialov; Michael Yu. Pavlov; Johan Elf; Kenn Gerdes; Måns Ehrenberg

2003-01-01

416

Apolipoprotein B48 is the Product of a Messenger RNA with an Organ-Specific In-Frame Stop Codon  

Microsoft Academic Search

The primary structure of human apolipoprotein (apo) B-48 has been deduced and shown by a combination of DNA excess hybridization, sequencing of tryptic peptides, cloned complementary DNAs, and intestinal messenger RNAs (mRNAs) to be the product of an intestinal mRNA with an in-frame UAA stop codon resulting from a C to U change in the codon CAA encoding Gln2153 in

San-Hwan Chen; Geetha Habib; Chao-Yuh Yang; Zi-Wei Gu; Bo Rong Lee; Shi-Ai Weng; Steven R. Silberman; Sheng-Jian Cai; J. P. Deslypere; Maryvonne Rosseneu; Antonio M. Gotto; Wen-Hsiung Li; Lawrence Chan

1987-01-01

417

UV-induced mutations affecting codon 12 of the K- ras gene are suppressed by interferon-? in human RSa cells  

Microsoft Academic Search

K-ras gene sequences mutant at codon 12 were recovered following differential dot-blot hybridization of genomic DNA from human RSa cells up to 12 days after the cells had been irradiated with far-UV (principally 254 nm). By contrast, no mutant codon 12 sequences were recovered from cells which had been treated with 50 IU\\/ml human interferon (HuIFN)-? for 24 h prior

Nobuo Suzuki; Hideko Suzuki; Toshiharu Ishizuka; Hideo Yamamori; Hidetoshi Ino

1997-01-01

418

Technology Empowerment as a Determinant of Salesforce Technology Usage  

Microsoft Academic Search

Abstract The purpose,of,this research,was to investigate how salespeople technology empowerment,impacts,their usage of technology. Although empowerment,has been investigated in the area of sales, no research has yet investigated technology empowerment,and its impact on salespeople technology usage. The relationship between technology empowerment, a multidimensional construct composed of four underlying dimensions (competence, autonomy, motivation, and impact) and technology usage was tested using a

Amy Chou

419

Convergence and constraint in eukaryotic release factor 1 (eRF1) domain 1: the evolution of stop codon specificity  

PubMed Central

Class 1 release factor in eukaryotes (eRF1) recognizes stop codons and promotes peptide release from the ribosome. The ‘molecular mimicry’ hypothesis suggests that domain 1 of eRF1 is analogous to the tRNA anticodon stem–loop. Recent studies strongly support this hypothesis and several models for specific interactions between stop codons and residues in domain 1 have been proposed. In this study we have sequenced and identified novel eRF1 sequences across a wide diversity of eukaryotes and re-evaluated the codon-binding site by bioinformatic analyses of a large eRF1 dataset. Analyses of the eRF1 structure combined with estimates of evolutionary rates at amino acid sites allow us to define the residues that are under structural (i.e. those involved in intramolecular interactions) versus non-structural selective constraints. Furthermore, we have re-assessed convergent substitutions in the ciliate variant code eRF1s using maximum likelihood-based phylogenetic approaches. Our results favor the model proposed by Bertram et al. that stop codons bind to three ‘cavities’ on the protein surface, although we suggest that the stop codon may bind in the opposite orientation to the original model. We assess the feasibility of this alternative binding orientation with a triplet stop codon and the eRF1 domain 1 structures using molecular modeling techniques.

Inagaki, Yuji; Blouin, Christian; Doolittle, W. Ford; Roger, Andrew J.

2002-01-01

420

Cleaning optimization for reduced chemical usage  

SciTech Connect

The use of dilute SC-1 (NH40H:H202:H20) chemistry cleaning processes for particle removal from silicon surfaces has been investigated. Dilute chemistries can be highly effective, especially when high- frequency acoustic energy (megasonics) is applied. The high particle removal efficacy of the dilute chemistry processes presumably arises due to increased double layer effects caused by reduced ionic strength. Dilute chemistry SC- I solutions exhibit somewhat reduced efficacy for removal of certain light organics; however, when dilute SC-1 is used along with other pre-gate cleaning steps (e.g. HF, SC-2, and piranha), then the overall cleaning sequence is quite effective. In addition to providing robust cleaning processes, dilute chemistries also result in significantly lower chemical and rinse water usage. Waste water treatment requirements are also lessened when dilute chemistry cleaning solutions are employed.

Resnick, P.J.; Simonson, G.C.; Matlock, C.A.; Kelly, M.J.

1996-11-01

421

Usage-Oriented Topic Maps Building Approach  

NASA Astrophysics Data System (ADS)

In this paper, we present a collaborative and incremental construction approach of multilingual Topic Maps based on enrichment and merging techniques. In recent years, several Topic Map building approaches have been proposed endowed with different characteristics. Generally, they are dedicated to particular data types like text, semi-structured data, relational data, etc. We note also that most of these approaches take as input monolingual documents to build the Topic Map. The problem is that the large majority of resources available today are written in various languages, and these resources could be relevant even to non-native speakers. Thus, our work is driven towards a collaborative and incremental method for Topic Map construction from textual documents available in different languages. To enrich the Topic Map, we take as input a domain thesaurus and we propose also to explore the Topic Map usage which means available potential questions related to the source documents.

Ellouze, Nebrasse; Lammari, Nadira; Métais, Elisabeth; Ben Ahmed, Mohamed

422

Functional polypeptides can be synthesized from human mitochondrial transcripts lacking termination codons.  

PubMed Central

The human mitochondrial genome (mtDNA) is a small, circular DNA duplex found in multi-copy in the mitochondrial matrix. It is almost fully transcribed from both strands to produce large polycistronic RNA units that are processed and matured. The 13 mtDNA-encoded polypeptides are translated from mt-mRNAs that have been matured by polyadenylation of their free 3'-termini. A patient with clinical features consistent with an mtDNA disorder was recently shown to carry a microdeletion, resulting in the loss of the termination codon for MTATP6 and in its juxtaposition with MTCO3. Cell lines from this patient exhibited low steady-state levels of RNA14, the bi-cistronic transcript encoding subunits 6 and 8 of the F(o)F(1)-ATP synthase, complex V, consistent with a decreased stability. Recent reports of 'non-stop' mRNA decay systems in the cytosol have failed to determine the fate of gene products derived from transcripts lacking termination codons, although enhanced decay clearly required the 'non-stop' transcripts to be translated. We wished to determine whether functional translation products could still be expressed from non-stop transcripts in the human mitochondrion. Although a minor defect in complex V assembly was noted in the patient-derived cell lines, the steady-state level of ATPase 6 was similar to controls, consistent with the pattern of de novo mitochondrial protein synthesis. Moreover, no significant difference in ATP synthase activity could be detected. We conclude that, in the absence of a functional termination codon, although mitochondrial transcripts are more rapidly degraded, they are also translated to generate stable polypeptides that are successfully integrated into functional enzyme complexes.

Chrzanowska-Lightowlers, Zofia M A; Temperley, Richard J; Smith, Paul M; Seneca, Sara H; Lightowlers, Robert N

2004-01-01

423

P53 Codon 72 polymorphisms: a case-control study of gastric cancer and potential interactions.  

PubMed

P53 codon 72 polymorphisms have been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the interaction of select risk factors and p53 codon 72 polymorphisms in gastric cancer susceptibility. 155 gastric cancer cases and 134 cancer-free controls were enrolled at the Memorial Sloan Kettering Cancer Center (MSKCC) from November 1992 to November 1994. The crude odds ratio (OR1) associated with the (Pro/Pro) polymorphism and the risk of gastric cancer was 1.27 (0.70-2.33). Adjusting for age, sex, race and education (OR2) and further adjusting for BMI, calories, sodium, smoking, vitamin C, fiber, alcohol, fat, and H. pylori status (OR3) did not yield significant results. Significant joint effects were associated with high fat consumption (OR1=2.61 (95% CI:1.13-6.06); OR2=2.85 (95% CI:1.14-7.15) for total cancers and for proximal tumors (OR1=2.56 (95%CI:1.00-6.54)). The low vitamin C intake/high-risk polymorphism group (Pro/Pro) had an OR1 of 4.82 (95% CI: 1.72-13.45) and the OR2 was 6.19 (95% CI: 2.08-18.40) for distal tumors. The point estimates were increased for interaction odds ratios but not statistically significant (OR1=4.25 (95% CI: 0.66-27.50); OR2=4.73 (95% CI: 0.67-33.43); OR3=5.55 (95% CI: 0.66-46.47)). Further studies specifically looking at proximal and distal tumors are required to confirm any potential interaction between the p53 codon 72 polymorphisms and environmental risk, in particular low dietary vitamin C and high fat consumption. PMID:16111803

Sul, James; Yu, Guo-Pei; Lu, Qing-Yi; Lu, Ming-Lan; Setiawan, Veronica Wendy; Wang, Ming-Rong; Guo, Chun Hua; Yu, Shun-Zhang; Mu, Lina; Cai, Lin; Kurtz, Robert C; Zhang, Zuo-Feng

2005-08-19

424

Genetic Inactivation of Poliovirus Infectivity by Increasing the Frequencies of CpG and UpA Dinucleotides within and across Synonymous Capsid Region Codons? †  

PubMed Central

Replicative fitness of poliovirus can be modulated systematically by replacement of preferred capsid region codons with synonymous unpreferred codons. To determine the key genetic contributors to fitness reduction, we introduced different sets of synonymous codons into the capsid coding region of an infectious clone derived from the type 2 prototype strain MEF-1. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased sharply with increased frequencies of the dinucleotides CpG (suppressed in higher eukaryotes and most RNA viruses) and UpA (suppressed nearly universally). Replacement of MEF-1 capsid codons with the corresponding codons from another type 2 prototype strain (Lansing), a randomization of MEF-1 synonymous codons, increased the %G+C without increasing CpG, and reductions in the effective number of codons used had much smaller individual effects on fitness. Poliovirus fitness was reduced to the threshold of viability when CpG and UpA dinucleotides were saturated within and across synonymous codons of a capsid region interval representing only ?9% of the total genome. Codon replacements were associated with moderate decreases in total virion production but large decreases in the specific infectivities of intact poliovirions and viral RNAs. Replication of codon replacement viruses, but not MEF-1, was temperature sensitive at 39.5°C. Synthesis and processing of viral intracellular proteins were largely unaltered in most codon replacement constructs. Replacement of natural codons with synonymous codons with increased frequencies of CpG and UpA dinucleotides may offer a general approach to the development of attenuated vaccines with well-defined antigenicities and very high genetic stabilities.

Burns, Cara C.; Campagnoli, Ray; Shaw, Jing; Vincent, Annelet; Jorba, Jaume; Kew, Olen

2009-01-01

425

Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment  

SciTech Connect

Aminoacyl-tRNA synthetases (aaRSs) ensure faithful translation of mRNA into protein by coupling an amino acid to a set of tRNAs with conserved anticodon sequences. Here, we show that in mitochondria of Saccharomyces cerevisiae, a single aaRS (MST1) recognizes and aminoacylates two natural tRNAs that contain anticodon loops of different size and sequence. Besides a regular ?? with a threonine (Thr) anticodon, MST1 also recognizes an unusual ??, which contains an enlarged anticodon loop and an anticodon triplet that reassigns the CUN codons from leucine to threonine. Our data show that MST1 recognizes the anticodon loop in both tRNAs, but employs distinct recognition mechanisms. The size but not the sequence of the anticodon loop is critical for ?? recognition, whereas the anticodon sequence is essential for aminoacylation of ??. The crystal structure of MST1 reveals that, while lacking the N-terminal editing domain, the enzyme closely resembles the bacterial threonyl-tRNA synthetase (ThrRS). A detailed structural comparison with Escherichia coli ThrRS, which is unable to aminoacylate ??, reveals differences in the anticodon-binding domain that probably allow recognition of the distinct anticodon loops. Finally, our mutational and modeling analyses identify the structural elements in MST1 (e.g., helix {alpha}11) that define tRNA selectivity. Thus, MTS1 exemplifies that a single aaRS can recognize completely divergent anticodon loops of natural isoacceptor tRNAs and that in doing so it facilitates the reassignment of the genetic code in yeast mitochondria.

Ling, Jiqiang; Peterson, Kaitlyn M.; Simonovic, Ivana; Cho, Chris; Soll, Dieter; Simonovic, Miljan (Yale); (UIC)

2012-03-13

426

Constitutive high-level expression of a codon-optimized ?-fructosidase gene from the hyperthermophile Thermotoga maritima in Pichia pastoris.  

PubMed

Enzymes for use in the sugar industry are preferred to be thermotolerant. In this study, a synthetic codon-optimized gene encoding a highly thermostable ?-fructosidase (BfrA, EC 3.2.1.26) from the bacterium Thermotoga maritima was expressed in the yeast Pichia pastoris. The gradual increase of the transgene dosage from one to four copies under the control of the constitutive glyceraldehyde 3-phosphate dehydrogenase promoter had an additive effect on BfrA yield without causing cell toxicity. Maximal values of cell biomass (115 g/l, dry weight) and overall invertase activity (241 U/ml) were reached at 72 h in fed-batch fermentations using cane sugar as the main carbon source for growth. Secretion driven by the Saccharomyces cerevisiae ?-factor signal peptide resulted in periplasmic retention (44 %) and extracellular release (56 %) of BfrA. The presence of N-linked oligosaccharides did not influence the optimal activity, thermal stability, kinetic properties, substrate specificity, and exo-type action mode of the yeast-secreted BfrA in comparison to the native unglycosylated enzyme. Complete inversion of cane sugar at initial concentration of 60 % (w/v) was achieved by periplasmic BfrA in undisrupted cells reacting at pH 5.5 and 70 °C, with average productivity of 4.4 g of substrate hydrolyzed per grams of biomass (wet weight) per hour. The high yield of fully active glycosylated BfrA here attained by recombinant P. pastoris in a low-cost fermentation process appears to be attractive for the large-scale production of this thermostable enzyme useful for the manufacture of inverted sugar syrup. PMID:22821437

Menéndez, Carmen; Martínez, Duniesky; Trujillo, Luis E; Mazola, Yuliet; González, Ernesto; Pérez, Enrique R; Hernández, Lázaro

2012-07-21

427

Novel dominant ?-thalassemia: Hb Boston-Kuwait [codon 139/140(+T)].  

PubMed

Dominant ?-thalassemias exhibit a hybrid phenotype of unstable hemoglobin and ineffective erythropoiesis. Most arise from heterozygous ?-globin gene mutations in exons 3 or 2 and present in adulthood as thalassemia intermedia. We report a novel, de novo ?-globin mutation presenting in a toddler with features of thalassemia major and chromaturia. Hemoglobin Boston-Kuwait is an elongated ?-chain variant (163 amino acids) that results from a frameshift mutation caused by a thymidine insertion in codons 139/140. Hematopoietic stem cell transplant provided a successful alternative therapy for this severe form of dominant ?-thalassemia. PMID:23776097

Croteau, Stacy E; Luo, Hong-Yuan; Lehmann, Leslie E; Chui, David H K; Neufeld, Ellis J

2013-06-15

428

Likelihood models of somatic mutation and codon substitution in cancer genes.  

PubMed Central

The role of somatic mutation in cancer is well established and several genes have been identified that are frequent targets. This has enabled large-scale screening studies of the spectrum of somatic mutations in cancers of particular organs. Cancer gene mutation databases compile the results of many studies and can provide insight into the importance of specific amino acid sequences and functional domains in cancer, as well as elucidate aspects of the mutation process. Past studies of the spectrum of cancer mutations (in particular genes) have examined overall frequencies of mutation (at specific nucleotides) and of missense, nonsense, and silent substitution (at specific codons) both in the sequence as a whole and in a specific functional domain. Existing methods ignore features of the genetic code that allow some codons to mutate to missense, or stop, codons more readily than others (i.e., by one nucleotide change, vs. two or three). A new codon-based method to estimate the relative rate of substitution (fixation of a somatic mutation in a cancer cell lineage) of nonsense vs. missense mutations in different functional domains and in different tumor tissues is presented. Models that account for several potential influences on rates of somatic mutation and substitution in cancer progenitor cells and allow biases of mutation rates for particular dinucleotide sequences (CGs and dipyrimidines), transition vs. transversion bias, and variable rates of silent substitution across functional domains (useful in detecting investigator sampling bias) are considered. Likelihood-ratio tests are used to choose among models, using cancer gene mutation data. The method is applied to analyze published data on the spectrum of p53 mutations in cancers. A novel finding is that the ratio of the probability of nonsense to missense substitution is much lower in the DNA-binding and transactivation domains (ratios near 1) than in structural domains such as the linker, tetramerization (oligomerization), and proline-rich domains (ratios exceeding 100 in some tissues), implying that the specific amino acid sequence may be less critical in structural domains (e.g., amino acid changes less often lead to cancer). The transition vs. transversion bias and effect of CpG dinucleotides on mutation rates in p53 varied greatly across cancers of different organs, likely reflecting effects of different endogenous and exogenous factors influencing mutation in specific organs.

Yang, Ziheng; Ro, Simon; Rannala, Bruce

2003-01-01

429

Effects of Different Metaphor Usage on Hypertext Learning  

ERIC Educational Resources Information Center

|There are many studies that offer different opinions on the effects of hypertext usage as an educational tool. Given the differences of opinion, it is useful to research the effects of metaphor usage in hypertext education and the use of hypertext as an educational tool. In this study, the effects of metaphors' uses in constructing the…

Merdivan, Ece; Ozdener, Nesrin

2011-01-01

430

Towards a Fluid Spectrum Market for Exclusive Usage Rights  

Microsoft Academic Search

This paper focuses on highly fluid markets for trading exclusive spectrum usage-rights. The purpose of the paper is to underline the need for flexible usage-rights policies, as a core facilitator of such markets as well as to stress the need for a greater technical input to the debate. The paper builds on current work in the field of spectrum property

Linda Doyle; Tim Forde

2007-01-01

431

Towards usage control models: beyond traditional access control  

Microsoft Academic Search

In this paper we develop the concept of Usage Control (UCON) that encompasses traditional access control, trust management, and digital rights management and goes beyond them in its definition and scope. While usage control concepts have been mentioned off and on in the security literature for some time, there has been no systematic treatment so far. By unifying these three

Jaehong Park; Ravi S. Sandhu

2002-01-01

432

Emotions as determinants of electric car usage intention  

Microsoft Academic Search

In a sample of 1202 Belgians, the determining factors of the usage intention of an electric car and the differences between early and late usage intention segments are investigated. The Theory of Planned Behaviour (TPB) framework is extended with emotional reactions towards the electric car and car driving in general. Emotions and the attitude towards the electric car are the

Ingrid Moons; Patrick De Pelsmacker

2012-01-01

433

An Exploratory Study of Internet Addiction, Usage and Communication Pleasure.  

ERIC Educational Resources Information Center

This study examined the correlation between Internet addiction, usage, and communication pleasure. Research questions were: (1) What is computer network addiction? (2) How can one measure the degree of computer network addiction? (3) What is the correlation between the degree of users' network addiction and their network usage? (4) What is the…

Chou, Chien; Chou, Jung; Tyan, Nay-Ching Nancy

434

What Is the next Trend in Usage Statistics in Libraries?  

ERIC Educational Resources Information Center

In answering the question "What is the next trend in usage statistics in libraries?" an eclectic group of respondents has presented an assortment of possibilities, suggestions, complaints and, of course, questions of their own. Undoubtedly, usage statistics collection, interpretation, and application are areas of growth and increasing complexity…

King, Douglas

2009-01-01

435

Reviewing and Critiquing Computer Learning and Usage among Older Adults  

ERIC Educational Resources Information Center

|By searching the keywords of "older adult" and "computer" in ERIC, Academic Search Premier, and PsycINFO, this study reviewed 70 studies published after 1990 that address older adults' computer learning and usage. This study revealed 5 prominent themes among reviewed literature: (a) motivations and barriers of older adults' usage of computers,…

Kim, Young Sek

2008-01-01

436

Query suggestions for mobile search: understanding usage patterns  

Microsoft Academic Search

Entering search terms on mobile phones is a time consuming and cumbersome task. In this paper, we explore the usage patterns of query entry interfaces that display suggestions. Our primary goal is to build a usage model of query suggestions in order to provide user interface guidelines for mobile text prediction interfaces. We find that users who were asked to

Maryam Kamvar; Shumeet Baluja

2008-01-01

437

UCON LEGAL : a usage control model for HIPAA  

Microsoft Academic Search

Developing an access control system that satisfies the requirements expressed in regulations, such as the Health Insurance Portability and Accountability Act (HIPAA), can help ensure regulatory compliance in software systems. A usage control model that specifies the rules governing information access and usage, as expressed in law, is an important step towards achieving such compliance. Software systems that handle health

Ramya Gopalan; Annie Antón; Jon Doyle

2012-01-01

438

Addictive, dependent, compulsive? A study of mobile phone usage  

Microsoft Academic Search

In order to address the claims that mobile phone usage is addictive, a study was undertaken to categorize mobile phone usage behaviour based on the underlying motivation. Six categories were identified: addictive, compulsive, dependent, habitual, voluntary and mandatory. A survey of 184 students found that the behaviour cannot be conclusively categorized as any specific type, although there was stronger support

Val Hooper; You Zhou

2007-01-01

439

Benchmarking Usage Statistics in Collection Management Decisions for Serials  

ERIC Educational Resources Information Center

Usage statistics are an important metric for making decisions on serials. Although the University of Nevada, Las Vegas (UNLV) Libraries have been collecting usage statistics, the statistics had not frequently been used to make decisions and had not been included in collection development policy. After undergoing a collection assessment, the…

Tucker, Cory

2009-01-01

440

Influences on free samples usage within the luxury cosmetic market  

Microsoft Academic Search

Purpose – The goals of this paper are to determine the effectiveness of product sampling in terms of usage, to draw a consumer profile who is reactive to free samples and to determine product characteristics that would lead to free samples usage. Design\\/methodology\\/approach – An experiment and a questionnaire inquiry were conducted. An outlet database was also used. Perfume, skin

Insaf Ben Amor; Francis Guilbert

2009-01-01

441

Modifications modulate anticodon loop dynamics and codon recognition of E. coli tRNA(Arg1,2).  

PubMed

Three of six arginine codons are read by two tRNA(Arg) isoacceptors in Escherichia coli. The anticodon stem and loop of these isoacceptors (ASL(Arg1,2)) differs only in that the position 32 cytidine of tRNA(Arg1) is posttranscriptionally modified to 2-thiocytidine (s(2)C(32)). The tRNA(Arg1,2) are also modified at positions 34 (inosine, I(34)) and 37 (2-methyladenosine, m(2)A(37)). To investigate the roles of modifications in the structure and function, we analyzed six ASL(Arg1,2) constructs differing in their array of modifications by spectroscopy and codon binding assays. Thermal denaturation and circular dichroism spectroscopy indicated that modifications contribute thermodynamic and base stacking properties, resulting in more order but less stability. NMR-derived structures of the ASL(Arg1,2) showed that the solution structures of the ASLs were nearly identical. Surprisingly, none possessed the U-turn conformation required for effective codon binding on the ribosome. Yet, all ASL(Arg1,2) constructs efficiently bound the cognate CGU codon. Three ASLs with I(34) were able to decode CGC, whereas only the singly modified ASL(Arg1,2)(ICG) with I(34) was able to decode CGA. The dissociation constants for all codon bindings were physiologically relevant (0.4-1.4 ?M). However, with the introduction of s(2)C(32) or m(2)A(37) to ASL(Arg1,2)(ICG), the maximum amount of ASL bound to CGU and CGC was significantly reduced. These results suggest that, by allowing loop flexibility, the modifications modulate the conformation of the ASL(Arg1,2), which takes one structure free in solution and two others when bound to the cognate arginyl-tRNA synthetase or to codons on the ribosome where modifications reduce or restrict binding to specific codons. PMID:22240457

Cantara, William A; Bilbille, Yann; Kim, Jia; Kaiser, Rob; Leszczy?ska, Gra?yna; Malkiewicz, Andrzej; Agris, Paul F

2012-01-03

442

What should we measure? Conceptualizing usage in health information exchange  

PubMed Central

Under the provisions of the Health Information Technology for Economic & Clinical Health act providers need to demonstrate their ‘meaningful use’ of electronic health record systems' health information exchange (HIE) capability. HIE usage is not a simple construct, but the choice of its measurement must attend to the users, context, and objectives of the system being examined. This review examined how usage is reported in the existing literature and also what conceptualizations of usage might best reflect the nature and objectives of HIE. While existing literature on HIE usage included a diverse set of measures, most were theoretically weak, did not attend to the interplay of measure, level of analysis and architectural strategy, and did not reflect how HIE usage affected the actual process of care. Attention to these issues will provide greater insight into the effects of previously inaccessible information on medical decision-making and the process of care.

Jasperson, Jon

2010-01-01

443

Trofile HIV co-receptor usage assay.  

PubMed

Background: The introduction of CCR5 antagonists increases the options available for constructing therapeutic drug regimens for HIV-positive patients. However, as these drugs do not inhibit HIV variants that use the CXCR4 co-receptor, a pretreatment test is requir