Science.gov

Sample records for codon usage patterns

  1. Synonymous codon usage pattern in glycoprotein gene of rabies virus.

    PubMed

    Morla, Sudhir; Makhija, Aditi; Kumar, Sachin

    2016-06-10

    Rabies virus (RABV) is the causative agent of a fatal nervous system ailment. The disease is zoonotic and prevalent in many developing countries. The glycoprotein (G) of RABV is the major antigenic determinant of the virus and plays a pivotal role in its neurovirulence. Various aspects of 'G' protein biology have been explored, but the factors affecting the nucleotide choice and synonymous codon usage have never been reported. In the present study, we have analyzed the relative synonymous codon usage and effective number of codons (Nc) using 132 'G' protein genes of RABV. Corresponding analysis was used to calculate major trends in codon usage. The correlation between base composition and codon usage as well as the plot between Nc and GC3 suggest that mutational pressure is the major factor that influences the codon usage in the G gene of RABV. In addition, factors like aromaticity, aliphatic index and hydropathy have shown slight correlation suggesting that natural selection also contributes to the codon usage variations of the 'G' gene. In conclusion, codon usage bias in 'G' gene of RABV is mainly by mutational pressure and natural selection. PMID:26945626

  2. Codon usage patterns in Nematoda: analysis based on over 25 million codons in thirty-two species

    PubMed Central

    2006-01-01

    Background Codon usage has direct utility in molecular characterization of species and is also a marker for molecular evolution. To understand codon usage within the diverse phylum Nematoda, we analyzed a total of 265,494 expressed sequence tags (ESTs) from 30 nematode species. The full genomes of Caenorhabditis elegans and C. briggsae were also examined. A total of 25,871,325 codons were analyzed and a comprehensive codon usage table for all species was generated. This is the first codon usage table available for 24 of these organisms. Results Codon usage similarity in Nematoda usually persists over the breadth of a genus but then rapidly diminishes even within each clade. Globodera, Meloidogyne, Pristionchus, and Strongyloides have the most highly derived patterns of codon usage. The major factor affecting differences in codon usage between species is the coding sequence GC content, which varies in nematodes from 32% to 51%. Coding GC content (measured as GC3) also explains much of the observed variation in the effective number of codons (R = 0.70), which is a measure of codon bias, and it even accounts for differences in amino acid frequency. Codon usage is also affected by neighboring nucleotides (N1 context). Coding GC content correlates strongly with estimated noncoding genomic GC content (R = 0.92). On examining abundant clusters in five species, candidate optimal codons were identified that may be preferred in highly expressed transcripts. Conclusion Evolutionary models indicate that total genomic GC content, probably the product of directional mutation pressure, drives codon usage rather than the converse, a conclusion that is supported by examination of nematode genomes. PMID:26271136

  3. Codon usage and protein sequence pattern dependency in different organisms: A Bioinformatics approach.

    PubMed

    Foroughmand-Araabi, Mohammad-Hadi; Goliaei, Bahram; Alishahi, Kasra; Sadeghi, Mehdi; Goliaei, Sama

    2015-04-01

    Although it is known that synonymous codons are not chosen randomly, the role of the codon usage in gene regulation is not clearly understood, yet. Researchers have investigated the relation between the codon usage and various properties, such as gene regulation, translation rate, translation efficiency, mRNA stability, splicing, and protein domains. Recently, a universal codon usage based mechanism for gene regulation is proposed. We studied the role of protein sequence patterns on the codons usage by related genes. Considering a subsequence of a protein that matches to a pattern or motif, we showed that, parts of the genes, which are translated to this subsequence, use specific ratios of synonymous codons. Also, we built a multinomial logistic regression statistical model for codon usage, which considers the effect of patterns on codon usage. This model justifies the observed codon usage preference better than the classic organism dependent codon usage. Our results showed that the codon usage plays a role in controlling protein levels, for genes that participate in a specific biological function. This is the first time that this phenomenon is reported. PMID:25409941

  4. Bioinformatics analysis of codon usage patterns and influencing factors in Penaeus monodon nudivirus.

    PubMed

    Tyagi, Anuj; Singh, Niraj K; Gurtler, Volker; Karunasagar, Indrani

    2016-02-01

    Penaeus monodon nudivirus (PmNV) is one of the most important and most commonly reported shrimp viruses. In the present study, codon usage of PmNV was studied in detail. Based on effective number of codons (ENC) values, strong to low codon usage bias was observed in PmNV genes. Nucleotide composition-ENC correlation analysis and the GC3 versus ENC relationship indicated that compositional constraint has a major effect on codon usage of PmNV. At the whole-genome level, relative synonymous codon usage (RSCU) analysis showed almost complete antagonism between the codon usage pattern of PmNV and its host P. monodon. However, codon adaptive index (CAI) values indicated that forces of selective/translational constraints have been able to overcome this antagonism in some genes. PMID:26586333

  5. Codon usage patterns in Chinese bayberry (Myrica rubra) based on RNA-Seq data

    PubMed Central

    2013-01-01

    Background Codon usage analysis has been a classical topic for decades and has significances for studies of evolution, mRNA translation, and new gene discovery, etc. While the codon usage varies among different members of the plant kingdom, indicating the necessity for species-specific study, this work has mostly been limited to model organisms. Recently, the development of deep sequencing, especial RNA-Seq, has made it possible to carry out studies in non-model species. Result RNA-Seq data of Chinese bayberry was analyzed to investigate the bias of codon usage and codon pairs. High frequency codons (AGG, GCU, AAG and GAU), as well as low frequency ones (NCG and NUA codons) were identified, and 397 high frequency codon pairs were observed. Meanwhile, 26 preferred and 141 avoided neighboring codon pairs were also identified, which showed more significant bias than the same pairs with one or more intervening codons. Codon patterns were also analyzed at the plant kingdom, organism and gene levels. Changes during plant evolution were evident using RSCU (relative synonymous codon usage), which was even more significant than GC3s (GC content of 3rd synonymous codons). Nine GO categories were differentially and independently influenced by CAI (codon adaptation index) or GC3s, especially in 'Molecular function’ category. Within a gene, the average CAI increased from 0.720 to 0.785 in the first 50 codons, and then more slowly thereafter. Furthermore, the preferred as well as avoided codons at the position just following the start codon AUG were identified and discussed in relation to the key positions in Kozak sequences. Conclusion A comprehensive codon usage Table and number of high-frequency codon pairs were established. Bias in codon usage as well as in neighboring codon pairs was observed, and the significance of this in avoiding DNA mutation, increasing protein production and regulating protein synthesis rate was proposed. Codon usage patterns at three levels were

  6. Characterization of codon usage pattern and influencing factors in Japanese encephalitis virus.

    PubMed

    Singh, Niraj K; Tyagi, Anuj; Kaur, Rajinder; Verma, Ramneek; Gupta, Praveen K

    2016-08-01

    Recently, several outbreaks of Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV), have been reported and it has become cause of concern across the world. In this study, detailed analysis of JEV codon usage pattern was performed. The relative synonymous codon usage (RSCU) values along with mean effective number of codons (ENC) value of 55.30 indicated the presence of low codon usages bias in JEV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations of A3s, U3s, G3s, C3s, GC3s, ENC values, with overall nucleotide contents (A%, U%, G%, C%, and GC%). The correlation analysis of A3s, U3s, G3s, C3s, GC3s, with axis values of correspondence analysis (CoA) further confirmed the role of mutational pressure. However, the correlation analysis of Gravy values and Aroma values with A3s, U3s, G3s, C3s, and GC3s, indicated the presence of natural selection on codon usage bias in addition to mutational pressure. The natural selection was further confirmed by codon adaptation index (CAI) analysis. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern to some extent. PMID:27189042

  7. Comparative Analysis of Codon Usage Bias Patterns in Microsporidian Genomes

    PubMed Central

    Xiang, Heng; Zhang, Ruizhi; Butler, Robert R.; Liu, Tie; Zhang, Li; Pombert, Jean-François; Zhou, Zeyang

    2015-01-01

    The sub-3 Mbp genomes from microsporidian species of the Encephalitozoon genus are the smallest known among eukaryotes and paragons of genomic reduction and compaction in parasites. However, their diminutive stature is not characteristic of all Microsporidia, whose genome sizes vary by an order of magnitude. This large variability suggests that different evolutionary forces are applied on the group as a whole. In this study, we have compared the codon usage bias (CUB) between eight taxonomically distinct microsporidian genomes: Encephalitozoon intestinalis, Encephalitozoon cuniculi, Spraguea lophii, Trachipleistophora hominis, Enterocytozoon bieneusi, Nematocida parisii, Nosema bombycis and Nosema ceranae. While the CUB was found to be weak in all eight Microsporidia, nearly all (98%) of the optimal codons in S. lophii, T. hominis, E. bieneusi, N. parisii, N. bombycis and N. ceranae are fond of A/U in third position whereas most (64.6%) optimal codons in the Encephalitozoon species E. intestinalis and E. cuniculi are biased towards G/C. Although nucleotide composition biases are likely the main factor driving the CUB in Microsporidia according to correlation analyses, directed mutational pressure also likely affects the CUB as suggested by ENc-plots, correspondence and neutrality analyses. Overall, the Encephalitozoon genomes were found to be markedly different from the other microsporidians and, despite being the first sequenced representatives of this lineage, are uncharacteristic of the group as a whole. The disparities observed cannot be attributed solely to differences in host specificity and we hypothesize that other forces are at play in the lineage leading to Encephalitozoon species. PMID:26057384

  8. Comparative Analysis of Codon Usage Bias Patterns in Microsporidian Genomes.

    PubMed

    Xiang, Heng; Zhang, Ruizhi; Butler, Robert R; Liu, Tie; Zhang, Li; Pombert, Jean-François; Zhou, Zeyang

    2015-01-01

    The sub-3 Mbp genomes from microsporidian species of the Encephalitozoon genus are the smallest known among eukaryotes and paragons of genomic reduction and compaction in parasites. However, their diminutive stature is not characteristic of all Microsporidia, whose genome sizes vary by an order of magnitude. This large variability suggests that different evolutionary forces are applied on the group as a whole. In this study, we have compared the codon usage bias (CUB) between eight taxonomically distinct microsporidian genomes: Encephalitozoon intestinalis, Encephalitozoon cuniculi, Spraguea lophii, Trachipleistophora hominis, Enterocytozoon bieneusi, Nematocida parisii, Nosema bombycis and Nosema ceranae. While the CUB was found to be weak in all eight Microsporidia, nearly all (98%) of the optimal codons in S. lophii, T. hominis, E. bieneusi, N. parisii, N. bombycis and N. ceranae are fond of A/U in third position whereas most (64.6%) optimal codons in the Encephalitozoon species E. intestinalis and E. cuniculi are biased towards G/C. Although nucleotide composition biases are likely the main factor driving the CUB in Microsporidia according to correlation analyses, directed mutational pressure also likely affects the CUB as suggested by ENc-plots, correspondence and neutrality analyses. Overall, the Encephalitozoon genomes were found to be markedly different from the other microsporidians and, despite being the first sequenced representatives of this lineage, are uncharacteristic of the group as a whole. The disparities observed cannot be attributed solely to differences in host specificity and we hypothesize that other forces are at play in the lineage leading to Encephalitozoon species. PMID:26057384

  9. Analysis of synonymous codon usage patterns in seven different citrus species.

    PubMed

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

    2013-01-01

    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. PMID:23761955

  10. A Comparative Analysis of Synonymous Codon Usage Bias Pattern in Human Albumin Superfamily

    PubMed Central

    Mirsafian, Hoda; Mat Ripen, Adiratna; Singh, Aarti; Teo, Phaik Hwan; Merican, Amir Feisal; Mohamad, Saharuddin Bin

    2014-01-01

    Synonymous codon usage bias is an inevitable phenomenon in organismic taxa across the three domains of life. Though the frequency of codon usage is not equal across species and within genome in the same species, the phenomenon is non random and is tissue-specific. Several factors such as GC content, nucleotide distribution, protein hydropathy, protein secondary structure, and translational selection are reported to contribute to codon usage preference. The synonymous codon usage patterns can be helpful in revealing the expression pattern of genes as well as the evolutionary relationship between the sequences. In this study, synonymous codon usage bias patterns were determined for the evolutionarily close proteins of albumin superfamily, namely, albumin, α-fetoprotein, afamin, and vitamin D-binding protein. Our study demonstrated that the genes of the four albumin superfamily members have low GC content and high values of effective number of codons (ENC) suggesting high expressivity of these genes and less bias in codon usage preferences. This study also provided evidence that the albumin superfamily members are not subjected to mutational selection pressure. PMID:24707212

  11. Analysis of codon usage pattern evolution in avian rotaviruses and their preferred host.

    PubMed

    Kattoor, Jobin Jose; Malik, Yashpal Singh; Sasidharan, Aravind; Rajan, Vishnuraj Mangalathu; Dhama, Kuldeep; Ghosh, Souvik; Bányai, Krisztián; Kobayashi, Nobumichi; Singh, Raj Kumar

    2015-08-01

    Rotavirus infection is a worldwide problem, with occurrence of highly divergent viruses classified in 8 species (A-H). We report here the evolution assessment of codon usage patterns in virus-host system in avian rotavirus (AvRV) of species RVA, RVD, RVF and RVG (preferentially affecting birds). The nucleotide contents, codon usage bias (CUB), relative synonymous codon usage (RSCU), and effective number of codons (ENCs) values were investigated targeting overexpressing major inner capsid viral protein (VP6) of these AvRV species. The results confirm that the evolutionary characteristics influences the rotavirus (RV) genetic diversity and impact of host's natural selection on the AvRVs codons. Synonymous codon usage patterns were evaluated following multivariate statistical procedures on all available AvRV coding gene sequences. RSCU trees accommodated all AvRV species and preferred host sequences in one topology confirming greater imminence of AvRVs with the host chicken cell genes. Similarly, the codon adaptation index (CAI) results also displayed a higher adaptation of AvRVs to its chicken host. The codon preference analysis of RVs revealed that VP6 gene express more proficiently in the yeast system, whereas, codon optimization might be required for the effectual expression in Escherichia coli and Homo sapiens. The findings provide basic evidence on the dynamics of AvRV evolution and its host adaptation, which could be exploited for additional research on avian species in future. PMID:26086995

  12. Evolutionary characterization of Tembusu virus infection through identification of codon usage patterns.

    PubMed

    Zhou, Hao; Yan, Bing; Chen, Shun; Wang, Mingshu; Jia, Renyong; Cheng, Anchun

    2015-10-01

    Tembusu virus (TMUV) is a single-stranded, positive-sense RNA virus. As reported, TMUV infection has resulted in significant poultry losses, and the virus may also pose a threat to public health. To characterize TMUV evolutionarily and to understand the factors accounting for codon usage properties, we performed, for the first time, a comprehensive analysis of codon usage bias for the genomes of 60 TMUV strains. The most recently published TMUV strains were found to be widely distributed in coastal cities of southeastern China. Codon preference among TMUV genomes exhibits a low bias (effective number of codons (ENC)=53.287) and is maintained at a stable level. ENC-GC3 plots and the high correlation between composition constraints and principal component factor analysis of codon usage demonstrated that mutation pressure dominates over natural selection pressure in shaping the TMUV coding sequence composition. The high correlation between the major components of the codon usage pattern and hydrophobicity (Gravy) or aromaticity (Aromo) was obvious, indicating that properties of viral proteins also account for the observed variation in TMUV codon usage. Principal component analysis (PCA) showed that CQW1 isolated from Chongqing may have evolved from GX2013H or GX2013G isolated from Guangxi, thus indicating that TMUV likely disseminated from southeastern China to the mainland. Moreover, the preferred codons encoding eight amino acids were consistent with the optimal codons for human cells, indicating that TMUV may pose a threat to public health due to possible cross-species transmission (birds to birds or birds to humans). The results of this study not only have theoretical value for uncovering the characteristics of synonymous codon usage patterns in TMUV genomes but also have significant meaning with regard to the molecular evolutionary tendencies of TMUV. PMID:26205688

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

    PubMed

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

    2013-04-01

    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

  14. Genome-Wide Analysis of the Synonymous Codon Usage Patterns in Riemerella anatipestifer

    PubMed Central

    Liu, Jibin; Zhu, Dekang; Ma, Guangpeng; Liu, Mafeng; Wang, Mingshu; Jia, Renyong; Chen, Shun; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    Riemerella anatipestifer (RA) belongs to the Flavobacteriaceae family and can cause a septicemia disease in poultry. The synonymous codon usage patterns of bacteria reflect a series of evolutionary changes that enable bacteria to improve tolerance of the various environments. We detailed the codon usage patterns of RA isolates from the available 12 sequenced genomes by multiple codon and statistical analysis. Nucleotide compositions and relative synonymous codon usage (RSCU) analysis revealed that A or U ending codons are predominant in RA. Neutrality analysis found no significant correlation between GC12 and GC3 (p > 0.05). Correspondence analysis and ENc-plot results showed that natural selection dominated over mutation in the codon usage bias. The tree of cluster analysis based on RSCU was concordant with dendrogram based on genomic BLAST by neighbor-joining method. By comparative analysis, about 50 highly expressed genes that were orthologs across all 12 strains were found in the top 5% of high CAI value. Based on these CAI values, we infer that RA contains a number of predicted highly expressed coding sequences, involved in transcriptional regulation and metabolism, reflecting their requirement for dealing with diverse environmental conditions. These results provide some useful information on the mechanisms that contribute to codon usage bias and evolution of RA. PMID:27517915

  15. Genome-Wide Analysis of the Synonymous Codon Usage Patterns in Riemerella anatipestifer.

    PubMed

    Liu, Jibin; Zhu, Dekang; Ma, Guangpeng; Liu, Mafeng; Wang, Mingshu; Jia, Renyong; Chen, Shun; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    Riemerella anatipestifer (RA) belongs to the Flavobacteriaceae family and can cause a septicemia disease in poultry. The synonymous codon usage patterns of bacteria reflect a series of evolutionary changes that enable bacteria to improve tolerance of the various environments. We detailed the codon usage patterns of RA isolates from the available 12 sequenced genomes by multiple codon and statistical analysis. Nucleotide compositions and relative synonymous codon usage (RSCU) analysis revealed that A or U ending codons are predominant in RA. Neutrality analysis found no significant correlation between GC12 and GC₃ (p > 0.05). Correspondence analysis and ENc-plot results showed that natural selection dominated over mutation in the codon usage bias. The tree of cluster analysis based on RSCU was concordant with dendrogram based on genomic BLAST by neighbor-joining method. By comparative analysis, about 50 highly expressed genes that were orthologs across all 12 strains were found in the top 5% of high CAI value. Based on these CAI values, we infer that RA contains a number of predicted highly expressed coding sequences, involved in transcriptional regulation and metabolism, reflecting their requirement for dealing with diverse environmental conditions. These results provide some useful information on the mechanisms that contribute to codon usage bias and evolution of RA. PMID:27517915

  16. Gaining Insights into the Codon Usage Patterns of TP53 Gene across Eight Mammalian Species

    PubMed Central

    Mazumder, Tarikul Huda; Chakraborty, Supriyo

    2015-01-01

    TP53 gene is known as the “guardian of the genome” as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB) is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution. PMID:25807269

  17. Codon Usage Patterns in Corynebacterium glutamicum: Mutational Bias, Natural Selection and Amino Acid Conservation.

    PubMed

    Liu, Guiming; Wu, Jinyu; Yang, Huanming; Bao, Qiyu

    2010-01-01

    The alternative synonymous codons in Corynebacterium glutamicum, a well-known bacterium used in industry for the production of amino acid, have been investigated by multivariate analysis. As C. glutamicum is a GC-rich organism, G and C are expected to predominate at the third position of codons. Indeed, overall codon usage analyses have indicated that C and/or G ending codons are predominant in this organism. Through multivariate statistical analysis, apart from mutational selection, we identified three other trends of codon usage variation among the genes. Firstly, the majority of highly expressed genes are scattered towards the positive end of the first axis, whereas the majority of lowly expressed genes are clustered towards the other end of the first axis. Furthermore, the distinct difference in the two sets of genes was that the C ending codons are predominate in putatively highly expressed genes, suggesting that the C ending codons are translationally optimal in this organism. Secondly, the majority of the putatively highly expressed genes have a tendency to locate on the leading strand, which indicates that replicational and transciptional selection might be invoked. Thirdly, highly expressed genes are more conserved than lowly expressed genes by synonymous and nonsynonymous substitutions among orthologous genes fromthe genomes of C. glutamicum and C. diphtheriae. We also analyzed other factors such as the length of genes and hydrophobicity that might influence codon usage and found their contributions to be weak. PMID:20445740

  18. Analysis of Codon Usage Patterns in Herbaceous Peony (Paeonia lactiflora Pall.) Based on Transcriptome Data.

    PubMed

    Wu, Yanqing; Zhao, Daqiu; Tao, Jun

    2015-01-01

    Codon usage bias, which exists in many genomes, is mainly determined by mutation and selection. To elucidate the genetic features and evolutionary history of herbaceous peony (Paeonia lactiflora), a well-known symbol of prosperity in China, we examined synonymous codon usage in 24,216 reconstructed genes from the P. lactiflora transcriptome. The mean GC content was 44.4%, indicating that the nucleotide content of P. lactiflora genes is slightly AT rich and GC poor. The P. lactiflora genome has a wide range of GC3 (GC content at the third synonymous codon position) distribution, with a significant correlation between GC12 and GC3. ENC (effective number of codons) analysis suggested that mutational bias played a major role in shaping codon usage. Parity Rule 2 (PR2) analysis revealed that GC and AU were not used proportionally. We identified 22 "optimal codons", most ending with an A or U. Our results suggested that nucleotide composition mutation bias and translational selection were the main driving factors of codon usage bias in P. lactiflora. These results lay the foundation for exploring the evolutionary mechanisms and heterologous expression of functionally-important proteins in P. lactiflora. PMID:26506393

  19. Analysis of Codon Usage Patterns in Herbaceous Peony (Paeonia lactiflora Pall.) Based on Transcriptome Data

    PubMed Central

    Wu, Yanqing; Zhao, Daqiu; Tao, Jun

    2015-01-01

    Codon usage bias, which exists in many genomes, is mainly determined by mutation and selection. To elucidate the genetic features and evolutionary history of herbaceous peony (Paeonia lactiflora), a well-known symbol of prosperity in China, we examined synonymous codon usage in 24,216 reconstructed genes from the P. lactiflora transcriptome. The mean GC content was 44.4%, indicating that the nucleotide content of P. lactiflora genes is slightly AT rich and GC poor. The P. lactiflora genome has a wide range of GC3 (GC content at the third synonymous codon position) distribution, with a significant correlation between GC12 and GC3. ENC (effective number of codons) analysis suggested that mutational bias played a major role in shaping codon usage. Parity Rule 2 (PR2) analysis revealed that GC and AU were not used proportionally. We identified 22 “optimal codons”, most ending with an A or U. Our results suggested that nucleotide composition mutation bias and translational selection were the main driving factors of codon usage bias in P. lactiflora. These results lay the foundation for exploring the evolutionary mechanisms and heterologous expression of functionally-important proteins in P. lactiflora. PMID:26506393

  20. Comparative investigation of the various determinants that influence the codon and amino acid usage patterns in the genus Bifidobacterium.

    PubMed

    Roy, Ayan; Mukhopadhyay, Subhasish; Sarkar, Indrani; Sen, Arnab

    2015-06-01

    Various strains of the genus Bifidobacterium are crucial members of the human, animal and insect gut, associated with beneficial probiotic activities. An extensive analysis on codon and amino acid usage of the GC rich genus Bifidobacterium has been executed in the present study. Multivariate statistical analysis revealed a coupled effect of GC compositional constraint and natural selection for translational efficiency to be operative in producing the observed codon usage variations. Gene expression level was inferred to be the most crucial factor governing the codon usage patterns. Amino acid usage was found to be influenced significantly by hydrophobic and aromatic character of the encoded proteins. Gene expressivity and protein energetic cost also had considerable impact on the differential mode of amino acid usage. The genus was found to strictly obey the cost-minimization hypothesis as was reflected from the amino acid usage patterns of the potential highly expressed gene products. Evolutionary analysis revealed that the highly expressed genes were candidates to extreme evolutionary selection pressure and indicated a high degree of conservation at the proteomic level. Interestingly, the complimentary strands of replication appeared to evolve under similar evolutionary constraints which might be addressed as a consequence of absence of replicational selection and lack of strand-specific asymmetry among the members of the genus. Thus, the present endeavor confers considerable know-how pertaining to the codon and amino acid usage intricacies in Bifidobacterium and might prove handy for further scientific investigations associated with the concerned domain. PMID:25842224

  1. The effect of context on synonymous codon usage in genes with low codon usage bias.

    PubMed Central

    Bulmer, M

    1990-01-01

    The effect of neighbouring bases on the usage of synonymous codons in genes with low codon usage bias in yeast and E. coli is examined. The codon adaptation index is employed to identify a group of genes in each organism with low codon usage bias, which are likely to be weakly expressed. A similar pattern is found in complementary sequences with respect to synonymous usage of A vs G or of U vs C. It is suggested that this may reflect an effect of context on mutation rates in weakly expressed genes. PMID:2190183

  2. Analysis of synonymous codon usage patterns in sixty-four different bivalve species

    PubMed Central

    De Moro, Gianluca; Venier, Paola; Pallavicini, Alberto

    2015-01-01

    Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates. PMID:26713259

  3. Effects of nucleotide usage on the synonymous codon usage patterns of biofilm-associated genes in Haemophilus parasuis.

    PubMed

    Wang, L Y; Ma, L N; Liu, Y S

    2016-01-01

    To provide a new perspective on the evolutionary characteristics shaping the genetic diversity of Haemophilus parasuis biofilms, the relative synonymous codon usage values, codon usage bias values, effective number of codons (ENC) values, codon adaptation index (CAI) values, and the base components were calculated. Our objective was to implement a comparative analysis to evaluate the dynamic evolution of biofilm-associated genes in H. parasuis. The analysis of genetic diversity provides evidence that some biofilm-associated genes have similar genetic features. However, other genes show some variations in genetic direction. Furthermore, preferential selection of the synonymous codons and amino acids is apparent in biofilm-associated genes. Additionally, the ENC and CAI data from this study all strongly suggested that biofilm-associated genes may depend on deoptimization to adapt to environmental changes, and the mutation effect of biofilm-associated genes in H. parasuis plays an important role in shaping the genetic features. Our results reveal that the mutations of biofilm-associated genes form a set of sophisticated strategies for combating the environmental changes arising from the host cell in the evolution of H. parasuis. PMID:27323145

  4. Codon usage trend in mitochondrial CYB gene.

    PubMed

    Uddin, Arif; Chakraborty, Supriyo

    2016-07-15

    Here we reported the pattern of codon usage and the factors which influenced the codon usage pattern in mitochondrial cytochrome B (MT-CYB) gene among pisces, aves and mammals. The F1 axis of correspondence analysis showed highly significant positive correlation with nucleobases A3, C and C3 and significant negative correlation with T and T3 while F2 of correspondence analysis showed significant positive correlation with C and C3 and significant negative correlation with A and A3. From the neutrality plot, it was evident that the GC12 was influenced by mutation pressure and natural selection with a ratio of 0.10/0.90=0.11 in pisces, 0.024/0.976=0.0245 in aves and in mammals 0.215/0.785=0.273, which indicated that the role of natural selection was more than mutation pressure on structuring the bases at the first and second codon positions. Natural selection played the major role; but compositional constraint and mutation pressure also played a significant role in codon usage pattern. Analysis of codon usage pattern has contributed to the better understanding of the mechanism of distribution of codons and the evolution of MT-CYB gene. PMID:27063508

  5. Di-codon Usage for Gene Classification

    NASA Astrophysics Data System (ADS)

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

    Classification of genes into biologically related groups facilitates inference of their functions. Codon usage bias has been described previously as a potential feature for gene classification. In this paper, we demonstrate that di-codon usage can further improve classification of genes. By using both codon and di-codon features, we achieve near perfect accuracies for the classification of HLA molecules into major classes and sub-classes. The method is illustrated on 1,841 HLA sequences which are classified into two major classes, HLA-I and HLA-II. Major classes are further classified into sub-groups. A binary SVM using di-codon usage patterns achieved 99.95% accuracy in the classification of HLA genes into major HLA classes; and multi-class SVM achieved accuracy rates of 99.82% and 99.03% for sub-class classification of HLA-I and HLA-II genes, respectively. Furthermore, by combining codon and di-codon usages, the prediction accuracies reached 100%, 99.82%, and 99.84% for HLA major class classification, and for sub-class classification of HLA-I and HLA-II genes, respectively.

  6. Modal Codon Usage: Assessing the Typical Codon Usage of a Genome

    PubMed Central

    Davis, James J.; Olsen, Gary J.

    2010-01-01

    Most genomes are heterogeneous in codon usage, so a codon usage study should start by defining the codon usage that is typical to the genome. Although this is commonly taken to be the genomewide average, we propose that the mode—the codon usage that matches the most genes—provides a more useful approximation of the typical codon usage of a genome. We provide a method for estimating the modal codon usage, which utilizes a continuous approximation to the number of matching genes and a simplex optimization. In a survey of bacterial and archaeal genomes, as many as 20% more of the genes in a given genome match the modal codon usage than the average codon usage. We use the mode to examine the evolution of the multireplicon genomes of Agrobacterium tumefaciens C58 and Borrelia burgdorferi B31. In A. tumefaciens, the circular and linear chromosomes are characterized by a common “chromosome-like” codon usage, whereas both plasmids share a distinct “plasmid-like” codon usage. In B. burgdorferi, in addition to different codon-usage biases on the leading and lagging strands of DNA replication found by McInerney (McInerney JO. 1998. Replicational and transcriptional selection on codon usage in Borrelia burgdorferi. Proc Natl Acad Sci USA. 95:10698–10703), we also detect a codon-usage similarity between linear plasmid lp38 and the leading strand of the chromosome and a high similarity among the cp32 family of plasmids. PMID:20018979

  7. Genome-wide analysis of codon usage bias in Ebolavirus.

    PubMed

    Cristina, Juan; Moreno, Pilar; Moratorio, Gonzalo; Musto, Héctor

    2015-01-22

    Ebola virus (EBOV) is a member of the family Filoviridae and its genome consists of a 19-kb, single-stranded, negative sense RNA. EBOV is subdivided into five distinct species with different pathogenicities, being Zaire ebolavirus (ZEBOV) the most lethal species. The interplay of codon usage among viruses and their hosts is expected to affect overall viral survival, fitness, evasion from host's immune system and evolution. In the present study, we performed comprehensive analyses of codon usage and composition of ZEBOV. Effective number of codons (ENC) indicates that the overall codon usage among ZEBOV strains is slightly biased. Different codon preferences in ZEBOV genes in relation to codon usage of human genes were found. Highly preferred codons are all A-ending triplets, which strongly suggests that mutational bias is a main force shaping codon usage in ZEBOV. Dinucleotide composition also plays a role in the overall pattern of ZEBOV codon usage. ZEBOV does not seem to use the most abundant tRNAs present in the human cells for most of their preferred codons. PMID:25445348

  8. Codon catalog usage and the genome hypothesis.

    PubMed Central

    Grantham, R; Gautier, C; Gouy, M; Mercier, R; Pavé, A

    1980-01-01

    Frequencies for each of the 61 amino acid codons have been determined in every published mRNA sequence of 50 or more codons. The frequencies are shown for each kind of genome and for each individual gene. A surprising consistency of choices exists among genes of the same or similar genomes. Thus each genome, or kind of genome, appears to possess a "system" for choosing between codons. Frameshift genes, however, have widely different choice strategies from normal genes. Our work indicates that the main factors distinguishing between mRNA sequences relate to choices among degenerate bases. These systematic third base choices can therefore be used to establish a new kind of genetic distance, which reflects differences in coding strategy. The choice patterns we find seem compatible with the idea that the genome and not the individual gene is the unit of selection. Each gene in a genome tends to conform to its species' usage of the codon catalog; this is our genome hypothesis. PMID:6986610

  9. Codon usage in Chlamydia trachomatis is the result of strand-specific mutational biases and a complex pattern of selective forces

    PubMed Central

    Romero, Héctor; Zavala, Alejandro; Musto, Héctor

    2000-01-01

    The patterns of synonymous codon choices of the completely sequenced genome of the bacterium Chlamydia trachomatis were analysed. We found that the most important source of variation among the genes results from whether the sequence is located on the leading or lagging strand of replication, resulting in an over representation of G or C, respectively. This can be explained by different mutational biases associated to the different enzymes that replicate each strand. Next we found that most highly expressed sequences are located on the leading strand of replication. From this result, replicational-transcriptional selection can be invoked. Then, when the genes located on the leading strand are studied separately, the correspondence analysis detects a principal trend which discriminates between lowly and highly expressed sequences, the latter displaying a different codon usage pattern than the former, suggesting selection for translation, which is reinforced by the fact that Ks values between orthologous sequences from C.trachomatis and Chlamydia pneumoniae are much smaller in highly expressed genes. Finally, synonymous codon choices appear to be influenced by the hydropathy of each encoded protein and by the degree of amino acid conservation. Therefore, synonymous codon usage in C.trachomatis seems to be the result of a very complex balance among different factors, which rises the problem of whether the forces driving codon usage patterns among microorganisms are rather more complex than generally accepted. PMID:10773076

  10. Genome-Wide Analysis of Codon Usage Bias in Epichloë festucae.

    PubMed

    Li, Xiuzhang; Song, Hui; Kuang, Yu; Chen, Shuihong; Tian, Pei; Li, Chunjie; Nan, Zhibiao

    2016-01-01

    Analysis of codon usage data has both practical and theoretical applications in understanding the basics of molecular biology. Differences in codon usage patterns among genes reflect variations in local base compositional biases and the intensity of natural selection. Recently, there have been several reports related to codon usage in fungi, but little is known about codon usage bias in Epichloë endophytes. The present study aimed to assess codon usage patterns and biases in 4870 sequences from Epichloë festucae, which may be helpful in revealing the constraint factors such as mutation or selection pressure and improving the bioreactor on the cloning, expression, and characterization of some special genes. The GC content with 56.41% is higher than the AT content (43.59%) in E. festucae. The results of neutrality and effective number of codons plot analyses showed that both mutational bias and natural selection play roles in shaping codon usage in this species. We found that gene length is strongly correlated with codon usage and may contribute to the codon usage patterns observed in genes. Nucleotide composition and gene expression levels also shape codon usage bias in E. festucae. E. festucae exhibits codon usage bias based on the relative synonymous codon usage (RSCU) values of 61 sense codons, with 25 codons showing an RSCU larger than 1. In addition, we identified 27 optimal codons that end in a G or C. PMID:27428961

  11. Genome-Wide Analysis of Codon Usage Bias in Epichloë festucae

    PubMed Central

    Li, Xiuzhang; Song, Hui; Kuang, Yu; Chen, Shuihong; Tian, Pei; Li, Chunjie; Nan, Zhibiao

    2016-01-01

    Analysis of codon usage data has both practical and theoretical applications in understanding the basics of molecular biology. Differences in codon usage patterns among genes reflect variations in local base compositional biases and the intensity of natural selection. Recently, there have been several reports related to codon usage in fungi, but little is known about codon usage bias in Epichloë endophytes. The present study aimed to assess codon usage patterns and biases in 4870 sequences from Epichloë festucae, which may be helpful in revealing the constraint factors such as mutation or selection pressure and improving the bioreactor on the cloning, expression, and characterization of some special genes. The GC content with 56.41% is higher than the AT content (43.59%) in E. festucae. The results of neutrality and effective number of codons plot analyses showed that both mutational bias and natural selection play roles in shaping codon usage in this species. We found that gene length is strongly correlated with codon usage and may contribute to the codon usage patterns observed in genes. Nucleotide composition and gene expression levels also shape codon usage bias in E. festucae. E. festucae exhibits codon usage bias based on the relative synonymous codon usage (RSCU) values of 61 sense codons, with 25 codons showing an RSCU larger than 1. In addition, we identified 27 optimal codons that end in a G or C. PMID:27428961

  12. Bicluster Pattern of Codon Context Usages between Flavivirus and Vector Mosquito Aedes aegypti: Relevance to Infection and Transcriptional Response of Mosquito Genes

    PubMed Central

    Behura, Susanta K.; Severson, David W.

    2014-01-01

    The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in most of the subtropical and tropical countries. Besides DENV, yellow fever virus (YFV) is also transmitted by A. aegypti. Susceptibility of A. aegypti to West Nile virus (WNV) has also been confirmed. Although studies have indicated correlation of codon bias between flaviviridae and their animal/insect hosts, it is not clear if codon sequences have any relation to susceptibility of A. aegypti to DENV, YFV and WNV. In the current study, usages of codon context sequences (codon pairs for neighboring amino acids) of the vector (A. aegypti) genome as well as the flaviviral genomes are investigated. We used bioinformatics methods to quantify codon context bias in a genome-wide manner of A. aegypti as well as DENV, WNV and YFV sequences. Mutual information statistics was applied to perform bicluster analysis of codon context bias between vector and flaviviral sequences. Functional relevance of the bicluster pattern was inferred from published microarray data. Our study shows that codon context bias of DENV, WNV and YFV sequences varies in a bicluster manner with that of specific sets of genes of A. aegypti. Many of these mosquito genes are known to be differentially expressed in response to flaviviral infection suggesting that codon context sequences of A. aegypti and the flaviviruses may play a role in the susceptible interaction between flaviviruses and this mosquito. The bias inusages of codon context sequences likely has a functional association with susceptibility of A. aegypti to flaviviral infection. The results from this study will allow us to conduct hypothesis driven tests to examine the role of codon contexts bias in evolution of vector-virus interactions at the molecular level. PMID:24838953

  13. [Codon usage bias in the straw mushroom Volvariella volvacea].

    PubMed

    Jiang, Wei; Lü, Beibei; He, Jianhua; Wang, Jinbin; Wu, Xiao; Wu, Guogan; Bao, Dapeng; Chen, Mingjie; Zhang, Jinsong; Tan, Qi; Tang, Xueming

    2014-09-01

    We analyzed the whole genome coding sequence of Volvariella volvacea to study the pattern utilization of codons by Codon W 1.4.2. As results, 24 optimal codons were identified. Moreover, the frequency of codons usage was calculated by CUSP program. We compared the frequency of codons usage of V. volvacea with other organisms including 6 modal value species (Homo sapiens, Saccharomys cerevisiae, Arabidopsis thalian, Mus musculus, Danio rerio and Drosophila melanogaster) and 4 edible fungi (Coprinopsis cinerea, Agaricus bisporus, Lentinula edodes and Pleurotus ostreatus). We found that there were less differences in 3 edible fungi (excluding Pleurotus ostreatus) than 6 modal value species, comparing with the frequency of codons usage of V. volvacea. With software SPSS16.0, cluster analysis which showed differences in the size of codon bias, reflects the evolutionary relationships between species, which can be used as a reference of evolutionary relationships of species. This was the first time for analysis the codon preference among the whole coding sequences of edible fungi, serving as theoretical basis to apply genetic engineering of V. volvacea. PMID:25720157

  14. Genome-wide analysis of synonymous codon usage in Huaiyangshan virus and other bunyaviruses.

    PubMed

    Luo, Xuelian; Liu, Qingzhen; Xiong, Yanwen; Ye, Changyun; Jin, Dong; Xu, Jianguo

    2015-12-01

    Huaiyangshan virus (HYSV) is a newly discovered bunyavirus, which is transmitted by ticks and causes hemorrhagic fever-like illness in human. The interplay of codon usage among viruses and their hosts is expected to affect viral survival, evasion from host's immune system and evolution. However, little is known about the codon usage in HYSV genome. In the present study, we analyzed synonymous codon usage in 120 available full-length HYSV sequences and performed a comparative analysis of synonymous codon usage patterns in HYSV and 42 other bunyaviruses. The relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C-ended. A comparative analysis of RSCU between HYSV and its hosts reflected that codon usage patterns of HYSV were mostly coincident with that of its hosts. Our data suggested that although mutational bias dominated codon usage, patterns of codon usage in HYSV were also under the influence of nature selection. Phylogenetic analysis based on RSCU values across different HYSV strains and 42 other bunyaviruses suggested that codon usage pattern in HYSV was the most similar with that of Uukuniemi virus among these bunyaviruses and that viruses belonged to Phlebovirus showed a diversity of codon usage patterns. PMID:26173646

  15. Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses

    PubMed Central

    Tong, Yigang

    2014-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp. mosquitoes. Its genome comprises a 12 kb single-strand positive-sense RNA. In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended. A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism. Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution. The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI). Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography. To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes. The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment. PMID:24595095

  16. Analysis of synonymous codon usage in porcine reproductive and respiratory syndrome virus.

    PubMed

    Liu, Yong-sheng; Zhou, Jian-hua; Chen, Hao-tai; Ma, Li-na; Ding, Yao-zhong; Wang, Meng; Zhang, Jie

    2010-08-01

    In this study, we calculated the relative synonymous codon usage (RSCU) values and codon usage bias (CUB) values to implement a comparative analysis of codon usage pattern of open reading frames (ORFs) which belong to the two main genotypes of porcine reproductive and respiratory syndrome virus (PRRSV). By analysis of synonymous codon usage values in each ORF of PRRSV, the optimal codons for most amino acids were all C or G-ended codons except GAU for Asp, CAU for His, UUU for Phe and CCU for Pro. The synonymous codon usage patterns in different ORFs of PRRSV were different and genetically conserved. Among them, ORF1a, ORF4, ORF5 and ORF7 could cluster these strains into the two main serotypes (EU and US). Due to mutational pressure, compositional constraint played an important role in shaping the synonymous codon usage pattern in different ORFs, and the synonymous codon usage diversity in ORFs was correlated with gene function. The degree of CUB for some particular amino acids under strong selection pressure probably served as a potential genetic marker for each ORF in PRRSV. However, gene length and translational selection in nature had no effect on the synonymous codon usage pattern in PRRSV. These conclusions could not only offer an insight into the synonymous codon usage pattern and differentiation of gene function, but also assist in understanding the discrepancy of evolution among ORFs in PRRSV. PMID:20438864

  17. Codon Usage Bias and Determining Forces in Taenia solium Genome.

    PubMed

    Yang, Xing; Ma, Xusheng; Luo, Xuenong; Ling, Houjun; Zhang, Xichen; Cai, Xuepeng

    2015-12-01

    The tapeworm Taenia solium is an important human zoonotic parasite that causes great economic loss and also endangers public health. At present, an effective vaccine that will prevent infection and chemotherapy without any side effect remains to be developed. In this study, codon usage patterns in the T. solium genome were examined through 8,484 protein-coding genes. Neutrality analysis showed that T. solium had a narrow GC distribution, and a significant correlation was observed between GC12 and GC3. Examination of an NC (ENC vs GC3s)-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENC (the effective number of codons) values were detected below the expected curve, suggesting that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally. We also identified 26 optimal codons in the T. solium genome, all of which ended with either a G or C residue. These optimal codons in the T. solium genome are likely consistent with tRNAs that are highly expressed in the cell, suggesting that mutational and translational selection forces are probably driving factors of codon usage bias in the T. solium genome. PMID:26797435

  18. Codon Usage Bias and Determining Forces in Taenia solium Genome

    PubMed Central

    Yang, Xing; Ma, Xusheng; Luo, Xuenong; Ling, Houjun; Zhang, Xichen; Cai, Xuepeng

    2015-01-01

    The tapeworm Taenia solium is an important human zoonotic parasite that causes great economic loss and also endangers public health. At present, an effective vaccine that will prevent infection and chemotherapy without any side effect remains to be developed. In this study, codon usage patterns in the T. solium genome were examined through 8,484 protein-coding genes. Neutrality analysis showed that T. solium had a narrow GC distribution, and a significant correlation was observed between GC12 and GC3. Examination of an NC (ENC vs GC3s)-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENC (the effective number of codons) values were detected below the expected curve, suggesting that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally. We also identified 26 optimal codons in the T. solium genome, all of which ended with either a G or C residue. These optimal codons in the T. solium genome are likely consistent with tRNAs that are highly expressed in the cell, suggesting that mutational and translational selection forces are probably driving factors of codon usage bias in the T. solium genome. PMID:26797435

  19. Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome

    PubMed Central

    Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Liu, Zhen-Xing; Hao, Le; Ma, Jiang-Yao; Li, Yu-Gu

    2016-01-01

    Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts. PMID:26927064

  20. Different patterns of codon usage in the overlapping polymerase and surface genes of hepatitis B virus suggest a de novo origin by modular evolution.

    PubMed

    Pavesi, Angelo

    2015-12-01

    The polymerase (P) and surface (S) genes of hepatitis B virus (HBV) show the longest gene overlap in animal viruses. Gene overlaps originate by the overprinting of a novel frame onto an ancestral pre-existing frame. Identifying which frame is ancestral and which frame is de novo (the genealogy of the overlap) is an appealing topic. However, the P/S overlap of HBV is an intriguing paradox, because both genes are indispensable for virus survival. Thus, the hypothesis of a primordial virus without the surface protein or without the polymerase makes no biological sense. With the aim to determine the genealogy of the overlap, the codon usage of the overlapping frames P and S was compared to that of the non-overlapping region. It was found that the overlap of human HBV had two patterns of codon usage. One was localized in the 59 one-third of the overlap and the other in the 39 two-thirds. By extending the analysis to non-human HBVs, it was found that this feature occurred in all hepadnaviruses. Under the assumption that the ancestral frame has a codon usage significantly closer to that of the non-overlapping region than the de novo frame, the ancestral frames in the 59 and 39 region of the overlap could be predicted. They were, respectively, frame S and frame P. These results suggest that the spacer domain of the polymerase and the S domain of the surface protein originated de novo by overprinting. They support a modular evolution hypothesis for the origin of the overlap. PMID:26446206

  1. Revelation of Influencing Factors in Overall Codon Usage Bias of Equine Influenza Viruses

    PubMed Central

    Bhatia, Sandeep; Sood, Richa; Selvaraj, Pavulraj

    2016-01-01

    Equine influenza viruses (EIVs) of H3N8 subtype are culprits of severe acute respiratory infections in horses, and are still responsible for significant outbreaks worldwide. Adaptability of influenza viruses to a particular host is significantly influenced by their codon usage preference, due to an absolute dependence on the host cellular machinery for their replication. In the present study, we analyzed genome-wide codon usage patterns in 92 EIV strains, including both H3N8 and H7N7 subtypes by computing several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis disclosed bias of preferred synonymous codons towards A/U-ended codons. The overall codon usage bias in EIVs was slightly lower, and mainly affected by the nucleotide compositional constraints as inferred from the RSCU and effective number of codon (ENc) analysis. Our data suggested that codon usage pattern in EIVs is governed by the interplay of mutation pressure, natural selection from its hosts and undefined factors. The H7N7 subtype was found less fit to its host (horse) in comparison to H3N8, by possessing higher codon bias, lower mutation pressure and much less adaptation to tRNA pool of equine cells. To the best of our knowledge, this is the first report describing the codon usage analysis of the complete genomes of EIVs. The outcome of our study is likely to enhance our understanding of factors involved in viral adaptation, evolution, and fitness towards their hosts. PMID:27119730

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    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.

  3. Analysis of synonymous codon usage in spike protein gene of infectious bronchitis virus.

    PubMed

    Makhija, Aditi; Kumar, Sachin

    2015-12-01

    Infectious bronchitis virus (IBV) is responsible for causing respiratory, renal, and urogenital diseases in poultry. IBV infection in poultry leads to high mortality rates in affected flocks and to severe economic losses due to a drop in egg production and a reduced gain in live weight of the broiler birds. IBV-encoded spike protein (S) is the major protective immunogen for the host. Although the functions of the S protein have been well studied, the factors shaping synonymous codon usage bias and nucleotide composition in the S gene have not been reported yet. In the present study, we analyzed the relative synonymous codon usage and effective number of codons (Nc) using the 53 IBV S genes. The major trend in codon usage variation was studied using correspondence analysis. The plot of Nc values against GC3 as well as the correlation between base composition and codon usage bias suggest that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in the S gene. Interestingly, no association of aromaticity, degree of hydrophobicity, and aliphatic index was observed with the codon usage variation in IBV S genes. The study represents a comprehensive analysis of IBV S gene codon usage patterns and provides a basic understanding of the codon usage bias. PMID:26452019

  4. Codon Usage Domains over Bacterial Chromosomes

    PubMed Central

    Bailly-Bechet, Marc; Danchin, Antoine; Iqbal, Mudassar; Marsili, Matteo; Vergassola, Massimo

    2006-01-01

    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 the organisms is found to be related to expression levels, as expected, but other groups feature an over-representation of genes belonging to different functional groups, namely horizontally transferred genes, motility, and intermediary metabolism. Furthermore, we show that genes with a similar bias tend to be close to each other on the chromosome and organized in coherent domains, more extended than operons, demonstrating a role of translation in structuring bacterial chromosomes. It is argued that a sizeable contribution to this effect comes from the dynamical compartimentalization induced by the recycling of tRNAs, leading to gene expression rates dependent on their genomic and expression context. PMID:16683018

  5. Analysis of the synonymous codon usage bias in recently emerged enterovirus D68 strains.

    PubMed

    Karniychuk, Uladzimir U

    2016-09-01

    Understanding the codon usage pattern of a pathogen and relationship between pathogen and host's codon usage patterns has fundamental and applied interests. Enterovirus D68 (EV-D68) is an emerging pathogen with a potentially high public health significance. In the present study, the synonymous codon usage bias of 27 recently emerged, and historical EV-D68 strains was analyzed. In contrast to previously studied enteroviruses (enterovirus 71 and poliovirus), EV-D68 and human host have a high discrepancy between favored codons. Analysis of viral synonymous codon usage bias metrics, viral nucleotide/dinucleotide compositional parameters, and viral protein properties showed that mutational pressure is more involved in shaping the synonymous codon usage bias of EV-D68 than translation selection. Computation of codon adaptation indices allowed to estimate expression potential of the EV-D68 genome in several commonly used laboratory animals. This approach requires experimental validation and may provide an auxiliary tool for the rational selection of laboratory animals to model emerging viral diseases. Enterovirus D68 genome compositional and codon usage data can be useful for further pathogenesis, animal model, and vaccine design studies. PMID:27364082

  6. The characteristics of synonymous codon usage in the initial and terminal translation regions of encephalomyocarditis virus.

    PubMed

    Ma, X-X; Feng, Y-P; Liu, J-L; Zhao, Y-Q; Chen, L; Guo, P-H; Guo, J-Z; Ma, Z-R

    2014-01-01

    The synonymous codon usage patterns in the initial and terminal translation regions (ITR, TTR) of the whole coding sequence of encephalomyocarditis virus (EMCV) were analyzed in relation to those in its natural hosts using the sequences accessible in databases. In general, some low-usage host codons were found over-represented in the ITR and TTR of the virus, while some high-usage host codons were found under-represented in the two viral regions. These relationships are thought to participate in the regulation of the speed of translation of viral proteins and in the suppression of ribosomal traffic jams, both aiming at the increase of virus yields. PMID:24720745

  7. Analysis of amino acid and codon usage in Paramecium bursaria.

    PubMed

    Dohra, Hideo; Fujishima, Masahiro; Suzuki, Haruo

    2015-10-01

    The ciliate Paramecium bursaria harbors the green-alga Chlorella symbionts. We reassembled the P. bursaria transcriptome to minimize falsely fused transcripts, and investigated amino acid and codon usage using the transcriptome data. Surface proteins preferentially use smaller amino acid residues like cysteine. Unusual synonymous codon and amino acid usage in highly expressed genes can reflect a balance between translational selection and other factors. A correlation of gene expression level with synonymous codon or amino acid usage is emphasized in genes down-regulated in symbiont-bearing cells compared to symbiont-free cells. Our results imply that the selection is associated with P. bursaria-Chlorella symbiosis. PMID:26341535

  8. Selective Factors Associated with the Evolution of Codon Usage in Natural Populations of Arboviruses

    PubMed Central

    Velazquez-Salinas, Lauro; Zarate, Selene; Eschbaumer, Michael; Pereira Lobo, Francisco; Gladue, Douglas P.; Arzt, Jonathan; Novella, Isabel S.; Rodriguez, Luis L.

    2016-01-01

    Arboviruses (arthropod borne viruses) have life cycles that include both vertebrate and invertebrate hosts with substantial differences in vector and host specificity between different viruses. Most arboviruses utilize RNA for their genetic material and are completely dependent on host tRNAs for their translation, suggesting that virus codon usage could be a target for selection. In the current study we analyzed the relative synonymous codon usage (RSCU) patterns of 26 arboviruses together with 25 vectors and hosts, including 8 vertebrates and 17 invertebrates. We used hierarchical cluster analysis (HCA) and principal component analysis (PCA) to identify trends in codon usage. HCA demonstrated that the RSCU of arboviruses reflects that of their natural hosts, but not that of dead-end hosts. Of the two major components identified by PCA, the first accounted for 62.1% of the total variance, and among the 59 codons analyzed in this study, the leucine codon CTG had the highest correlation with the first principal component, however isoleucine had the highest correlation during amino acid analysis. Nucleotide and dinucleotide composition were the variables that explained most of the total codon usage variance. The results suggest that the main factors driving the evolution of codon usage in arboviruses is based on the nucleotide and dinucleotide composition present in the host. Comparing codon usage of arboviruses and potential vector hosts can help identifying potential vectors for emerging arboviruses. PMID:27455096

  9. Selective Factors Associated with the Evolution of Codon Usage in Natural Populations of Arboviruses.

    PubMed

    Velazquez-Salinas, Lauro; Zarate, Selene; Eschbaumer, Michael; Pereira Lobo, Francisco; Gladue, Douglas P; Arzt, Jonathan; Novella, Isabel S; Rodriguez, Luis L

    2016-01-01

    Arboviruses (arthropod borne viruses) have life cycles that include both vertebrate and invertebrate hosts with substantial differences in vector and host specificity between different viruses. Most arboviruses utilize RNA for their genetic material and are completely dependent on host tRNAs for their translation, suggesting that virus codon usage could be a target for selection. In the current study we analyzed the relative synonymous codon usage (RSCU) patterns of 26 arboviruses together with 25 vectors and hosts, including 8 vertebrates and 17 invertebrates. We used hierarchical cluster analysis (HCA) and principal component analysis (PCA) to identify trends in codon usage. HCA demonstrated that the RSCU of arboviruses reflects that of their natural hosts, but not that of dead-end hosts. Of the two major components identified by PCA, the first accounted for 62.1% of the total variance, and among the 59 codons analyzed in this study, the leucine codon CTG had the highest correlation with the first principal component, however isoleucine had the highest correlation during amino acid analysis. Nucleotide and dinucleotide composition were the variables that explained most of the total codon usage variance. The results suggest that the main factors driving the evolution of codon usage in arboviruses is based on the nucleotide and dinucleotide composition present in the host. Comparing codon usage of arboviruses and potential vector hosts can help identifying potential vectors for emerging arboviruses. PMID:27455096

  10. SENCA: A Multilayered Codon Model to Study the Origins and Dynamics of Codon Usage.

    PubMed

    Pouyet, Fanny; Bailly-Bechet, Marc; Mouchiroud, Dominique; Guéguen, Laurent

    2016-01-01

    Gene sequences are the target of evolution operating at different levels, including the nucleotide, codon, and amino acid levels. Disentangling the impact of those different levels on gene sequences requires developing a probabilistic model with three layers. Here we present SENCA (site evolution of nucleotides, codons, and amino acids), a codon substitution model that separately describes 1) nucleotide processes which apply on all sites of a sequence such as the mutational bias, 2) preferences between synonymous codons, and 3) preferences among amino acids. We argue that most synonymous substitutions are not neutral and that SENCA provides more accurate estimates of selection compared with more classical codon sequence models. We study the forces that drive the genomic content evolution, intraspecifically in the core genome of 21 prokaryotes and interspecifically for five Enterobacteria. We retrieve the existence of a universal mutational bias toward AT, and that taking into account selection on synonymous codon usage has consequences on the measurement of selection on nonsynonymous substitutions. We also confirm that codon usage bias is mostly driven by selection on preferred codons. We propose new summary statistics to measure the relative importance of the different evolutionary processes acting on sequences. PMID:27401173

  11. SENCA: A Multilayered Codon Model to Study the Origins and Dynamics of Codon Usage

    PubMed Central

    Pouyet, Fanny; Bailly-Bechet, Marc; Mouchiroud, Dominique; Guéguen, Laurent

    2016-01-01

    Gene sequences are the target of evolution operating at different levels, including the nucleotide, codon, and amino acid levels. Disentangling the impact of those different levels on gene sequences requires developing a probabilistic model with three layers. Here we present SENCA (site evolution of nucleotides, codons, and amino acids), a codon substitution model that separately describes 1) nucleotide processes which apply on all sites of a sequence such as the mutational bias, 2) preferences between synonymous codons, and 3) preferences among amino acids. We argue that most synonymous substitutions are not neutral and that SENCA provides more accurate estimates of selection compared with more classical codon sequence models. We study the forces that drive the genomic content evolution, intraspecifically in the core genome of 21 prokaryotes and interspecifically for five Enterobacteria. We retrieve the existence of a universal mutational bias toward AT, and that taking into account selection on synonymous codon usage has consequences on the measurement of selection on nonsynonymous substitutions. We also confirm that codon usage bias is mostly driven by selection on preferred codons. We propose new summary statistics to measure the relative importance of the different evolutionary processes acting on sequences. PMID:27401173

  12. Mutation and Selection Cause Codon Usage and Bias in Mitochondrial Genomes of Ribbon Worms (Nemertea)

    PubMed Central

    Chen, Haixia; Sun, Shichun; Norenburg, Jon L.; Sundberg, Per

    2014-01-01

    The phenomenon of codon usage bias is known to exist in many genomes and it is mainly determined by mutation and selection. To understand the patterns of codon usage in nemertean mitochondrial genomes, we use bioinformatic approaches to analyze the protein-coding sequences of eight nemertean species. Neutrality analysis did not find a significant correlation between GC12 and GC3. ENc-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENc values are below it. ENc-plot suggested that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally and we propose that codons containing A or U at third position are used preferentially in nemertean species, regardless of whether corresponding tRNAs are encoded in the mitochondrial DNA. Context-dependent analysis indicated that the nucleotide at the second codon position slightly affects synonymous codon choices. These results suggested that mutational and selection forces are probably acting to codon usage bias in nemertean mitochondrial genomes. PMID:24454907

  13. Mutation and selection cause codon usage and bias in mitochondrial genomes of ribbon worms (Nemertea).

    PubMed

    Chen, Haixia; Sun, Shichun; Norenburg, Jon L; Sundberg, Per

    2014-01-01

    The phenomenon of codon usage bias is known to exist in many genomes and it is mainly determined by mutation and selection. To understand the patterns of codon usage in nemertean mitochondrial genomes, we use bioinformatic approaches to analyze the protein-coding sequences of eight nemertean species. Neutrality analysis did not find a significant correlation between GC12 and GC3. ENc-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENc values are below it. ENc-plot suggested that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally and we propose that codons containing A or U at third position are used preferentially in nemertean species, regardless of whether corresponding tRNAs are encoded in the mitochondrial DNA. Context-dependent analysis indicated that the nucleotide at the second codon position slightly affects synonymous codon choices. These results suggested that mutational and selection forces are probably acting to codon usage bias in nemertean mitochondrial genomes. PMID:24454907

  14. A backtranslation method based on codon usage strategy.

    PubMed Central

    Pesole, G; Attimonelli, M; Liuni, S

    1988-01-01

    This study describes a method for the backtranslation of an aminoacidic sequence, an extremely useful tool for various experimental approaches. It involves two computer programs CLUSTER and BACKTR written in Fortran 77 running on a VAX/VMS computer. CLUSTER generates a reliable codon usage table through a cluster analysis, based on a chi 2-like distance between the sequences. BACKTR produces backtranslated sequences according to different options when use is made of the codon usage table obtained in addition to selecting the least ambiguous potential oligonucleotide probes within an aminoacidic sequence. The method was tested by applying it to 158 yeast genes. PMID:3281142

  15. Mononucleotide and dinucleotide frequencies, and codon usage in poliovirion RNA.

    PubMed Central

    Rothberg, P G; Wimmer, E

    1981-01-01

    The polio type 1 (Mahoney) RNA sequence (1) has been analyzed in terms of the distribution of its mononucleotides, dinucleotides and trinucleotides (codons). The distribution of adenosine in the sequence is nonuniform, being lower at the 5' end and higher at the 3' end. The dinucleotide CG is relatively rare and the dinucleotides UG and CA are relatively more common than expected. Codon usage is decidedly nonrandom. Codons containing CG are avoided and those ending in adenosine are favored. The asymmetric use of mononucleotides, dinucleotides and codons in polio RNA is unexplained at the present time although the lowered CG frequency may be the result of a DNA origin for polio RNA. PMID:6275352

  16. Gene classification using codon usage and support vector machines.

    PubMed

    Ma, Jianmin; Nguyen, Minh N; Rajapakse, Jagath C

    2009-01-01

    A novel approach for gene classification, which adopts codon usage bias as input feature vector for classification by support vector machines (SVM) is proposed. The DNA sequence is first converted to a 59-dimensional feature vector where each element corresponds to the relative synonymous usage frequency of a codon. As the input to the classifier is independent of sequence length and variance, our approach is useful when the sequences to be classified are of different lengths, a condition that homology-based methods tend to fail. The method is demonstrated by using 1,841 Human Leukocyte Antigen (HLA) sequences which are classified into two major classes: HLA-I and HLA-II; each major class is further subdivided into sub-groups of HLA-I and HLA-II molecules. Using codon usage frequencies, binary SVM achieved accuracy rate of 99.3% for HLA major class classification and multi-class SVM achieved accuracy rates of 99.73% and 98.38% for sub-class classification of HLA-I and HLA-II molecules, respectively. The results show that gene classification based on codon usage bias is consistent with the molecular structures and biological functions of HLA molecules. PMID:19179707

  17. Solving the riddle of codon usage preferences: a test for translational selection

    PubMed Central

    Reis, Mario dos; Savva, Renos; Wernisch, Lorenz

    2004-01-01

    Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model. PMID:15448185

  18. Evolution of Synonymous Codon Usage in Neurospora tetrasperma and Neurospora discreta

    PubMed Central

    Whittle, C. A.; Sun, Y.; Johannesson, H.

    2011-01-01

    Neurospora comprises a primary model system for the study of fungal genetics and biology. In spite of this, little is known about genome evolution in Neurospora. For example, the evolution of synonymous codon usage is largely unknown in this genus. In the present investigation, we conducted a comprehensive analysis of synonymous codon usage and its relationship to gene expression and gene length (GL) in Neurospora tetrasperma and Neurospora discreta. For our analysis, we examined codon usage among 2,079 genes per organism and assessed gene expression using large-scale expressed sequenced tag (EST) data sets (279,323 and 453,559 ESTs for N. tetrasperma and N. discreta, respectively). Data on relative synonymous codon usage revealed 24 codons (and two putative codons) that are more frequently used in genes with high than with low expression and thus were defined as optimal codons. Although codon-usage bias was highly correlated with gene expression, it was independent of selectively neutral base composition (introns); thus demonstrating that translational selection drives synonymous codon usage in these genomes. We also report that GL (coding sequences [CDS]) was inversely associated with optimal codon usage at each gene expression level, with highly expressed short genes having the greatest frequency of optimal codons. Optimal codon frequency was moderately higher in N. tetrasperma than in N. discreta, which might be due to variation in selective pressures and/or mating systems. PMID:21402862

  19. A detailed comparative analysis of codon usage bias in Zika virus.

    PubMed

    Cristina, Juan; Fajardo, Alvaro; Soñora, Martín; Moratorio, Gonzalo; Musto, Héctor

    2016-09-01

    Zika virus (ZIKV) is a member of the family Flaviviridae and its genome consists of a single-stranded positive sense RNA molecule with 10,794 nucleotides. Clinical manifestations of disease caused by ZIKV infection range from asymptomatic cases to an influenza-like syndrome. There is an increasing concern about the possible relation among microcephaly and ZIKV infection. To get insight into the relation of codon usage among viruses and their hosts is extremely important to understand virus survival, fitness, evasion from host's immune system and evolution. In this study, we performed a comprehensive analysis of codon usage and composition of ZIKV. The overall codon usage among ZIKV strains is similar and slightly biased. Different codon preferences in ZIKV genes in relation to codon usage of human, Aedes aegypti and Aedes albopictus genes were found. Most of the highly frequent codons are A-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. G+C compositional constraint as well as dinucleotide composition also influence the codon usage of ZIKV. The results of these studies suggest that the emergence of ZIKV outside Africa, in the Pacific and the Americas may also be reflected in ZIKV codon usage. No significant differences were found in codon usage among strains isolated from microcephaly cases and the rest of strains from the Asian cluster enrolled in these studies. PMID:27449601

  20. Importance of codon usage for the temporal regulation of viral gene expression.

    PubMed

    Shin, Young C; Bischof, Georg F; Lauer, William A; Desrosiers, Ronald C

    2015-11-10

    The glycoproteins of herpesviruses and of HIV/SIV are made late in the replication cycle and are derived from transcripts that use an unusual codon usage that is quite different from that of the host cell. Here we show that the actions of natural transinducers from these two different families of persistent viruses (Rev of SIV and ORF57 of the rhesus monkey rhadinovirus) are dependent on the nature of the skewed codon usage. In fact, the transinducibility of expression of these glycoproteins by Rev and by ORF57 can be flipped simply by changing the nature of the codon usage. Even expression of a luciferase reporter could be made Rev dependent or ORF57 dependent by distinctive changes to its codon usage. Our findings point to a new general principle in which different families of persisting viruses use a poor codon usage that is skewed in a distinctive way to temporally regulate late expression of structural gene products. PMID:26504241

  1. Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding.

    PubMed

    Yu, Chien-Hung; Dang, Yunkun; Zhou, Zhipeng; Wu, Cheng; Zhao, Fangzhou; Sachs, Matthew S; Liu, Yi

    2015-09-01

    Codon usage bias is a universal feature of eukaryotic and prokaryotic genomes and has been proposed to regulate translation efficiency, accuracy, and protein folding based on the assumption that codon usage affects translation dynamics. The roles of codon usage in translation, however, are not clear and have been challenged by recent ribosome profiling studies. Here we used a Neurospora cell-free translation system to directly monitor the velocity of mRNA translation. We demonstrated that the preferred codons enhance the rate of translation elongation, whereas non-optimal codons slow elongation. Codon usage also controls ribosome traffic on mRNA. These conclusions were supported by ribosome profiling results in vitro and in vivo with template mRNAs designed to increase the signal-to-noise ratio. Finally, we demonstrate that codon usage regulates protein function by affecting co-translational protein folding. These results resolve a long-standing fundamental question and suggest the existence of a codon usage code for protein folding. PMID:26321254

  2. AT2-AT3-profiling: a new look at synonymous codon usage.

    PubMed

    Pluhar, Wolfgang

    2006-12-01

    The teleology of synonymous codon usage (SCU) still awaits a unifying concept. Here the 2nd codon letter of human mRNA-codons was graphically, aided by a computer program, put in relation to the 3rd codon letter, the carrier of SCU: AT2, the density of A+T in 2nd codon position, behaves to AT3, the analogous density of the 3rd codon position, mostly in an inverse fashion that can be expressed as typical figures: mRNAs with an overall AT-density below 50% have a tendency to produce bulky figures called "red dragons" (when redness is attributed to graph-areas, where AT3< AT2), while mRNAs with an AT-density above 50% produce a pattern called "harlequin" consisting of alternating red and blue (blueness, in analogy, when AT3>AT2) diamonds. With more diversion of AT3 from AT2, the harlequin patterns can assume the pattern of a "blue dragon". By analysing the mRNA of known proteins, these patterns can be correlated with certain functional regions: proteins with multiple transmembrane passages show bulky "red dragons", structural proteins with a high glycine- and proline content such as collagen result in "blue dragons". Non-coding mRNAs tend to show a balance between AT2 and AT3 and hence "harlequin patterns". Signal peptides usually code red due to a low AT3 with an AT2-density at the expectance level. With this technique DNA-sequences of as yet unknown functional meaning were scanned. When stretches of harlequin patterns appear interrupted by red or blue dragons, closer scrutiny of these stretches can reveal ORFs which deserve to be looked at more closely for their protein-informational content. At least in humans, SCU appears to follow protein-dependent AT2-density in a reciprocal fashion and does not seem to serve the purpose of influencing mRNA secondary structure which is discussed in depth. PMID:16930630

  3. Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD.

    PubMed

    Fu, Jingjing; Murphy, Katherine A; Zhou, Mian; Li, Ying H; Lam, Vu H; Tabuloc, Christine A; Chiu, Joanna C; Liu, Yi

    2016-08-01

    Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which manifests into changes in molecular rhythmicity and abnormal circadian behavioral output. This study provides an in vivo example that demonstrates the role of codon usage in determining protein structure and function in an animal system. These results suggest a universal mechanism in eukaryotes that uses a codon usage "code" within genetic codons to regulate cotranslational protein folding. PMID:27542830

  4. Online CME usage patterns.

    PubMed

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

    2011-01-01

    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

  5. Cytochrome P450 genes in coronary artery diseases: Codon usage analysis reveals genomic GC adaptation.

    PubMed

    Malakar, Arup Kumar; Halder, Binata; Paul, Prosenjit; Chakraborty, Supriyo

    2016-09-15

    Establishing codon usage biases are imperative for understanding the etiology of coronary artery diseases (CAD) as well as the genetic factors associated with these diseases. The aim of this study was to evaluate the contribution of 18 responsible cytochrome P450 (CYP) genes for the risk of CAD. Effective number of codon (Nc) showed a negative correlation with both GC3 and synonymous codon usage order (SCUO) suggesting an antagonistic relationship between codon usage and Nc of genes. The dinucleotide analysis revealed that CG and TA dinucleotides have the lowest odds ratio in these genes. Principal component analysis showed that GC composition has a profound effect in separating the genes along the first major axis. Our findings revealed that mutational pressure and natural selection could possibly be the major factors responsible for codon bias in these genes. The study not only offers an insight into the mechanisms of genomic GC adaptation, but also illustrates the complexity of CYP genes in CAD. PMID:27275533

  6. Comprehensive Analysis of Stop Codon Usage in Bacteria and Its Correlation with Release Factor Abundance*

    PubMed Central

    Korkmaz, Gürkan; Holm, Mikael; Wiens, Tobias; Sanyal, Suparna

    2014-01-01

    We present a comprehensive analysis of stop codon usage in bacteria by analyzing over eight million coding sequences of 4684 bacterial sequences. Using a newly developed program called “stop codon counter,” the frequencies of the three classical stop codons TAA, TAG, and TGA were analyzed, and a publicly available stop codon database was built. Our analysis shows that with increasing genomic GC content the frequency of the TAA codon decreases and that of the TGA codon increases in a reciprocal manner. Interestingly, the release factor 1-specific codon TAG maintains a more or less uniform frequency (∼20%) irrespective of the GC content. The low abundance of TAG is also valid with respect to expression level of the genes ending with different stop codons. In contrast, the highly expressed genes predominantly end with TAA, ensuring termination with either of the two release factors. Using three model bacteria with different stop codon usage (Escherichia coli, Mycobacterium smegmatis, and Bacillus subtilis), we show that the frequency of TAG and TGA codons correlates well with the relative steady state amount of mRNA and protein for release factors RF1 and RF2 during exponential growth. Furthermore, using available microarray data for gene expression, we show that in both fast growing and contrasting biofilm formation conditions, the relative level of RF1 is nicely correlated with the expression level of the genes ending with TAG. PMID:25217634

  7. Codon Usage Selection Can Bias Estimation of the Fraction of Adaptive Amino Acid Fixations.

    PubMed

    Matsumoto, Tomotaka; John, Anoop; Baeza-Centurion, Pablo; Li, Boyang; Akashi, Hiroshi

    2016-06-01

    A growing number of molecular evolutionary studies are estimating the proportion of adaptive amino acid substitutions (α) from comparisons of ratios of polymorphic and fixed DNA mutations. Here, we examine how violations of two of the model assumptions, neutral evolution of synonymous mutations and stationary base composition, affect α estimation. We simulated the evolution of coding sequences assuming weak selection on synonymous codon usage bias and neutral protein evolution, α = 0. We show that weak selection on synonymous mutations can give polymorphism/divergence ratios that yield α-hat (estimated α) considerably larger than its true value. Nonstationary evolution (changes in population size, selection, or mutation) can exacerbate such biases or, in some scenarios, give biases in the opposite direction, α-hat < α. These results demonstrate that two factors that appear to be prevalent among taxa, weak selection on synonymous mutations and non-steady-state nucleotide composition, should be considered when estimating α. Estimates of the proportion of adaptive amino acid fixations from large-scale analyses of Drosophila melanogaster polymorphism and divergence data are positively correlated with codon usage bias. Such patterns are consistent with α-hat inflation from weak selection on synonymous mutations and/or mutational changes within the examined gene trees. PMID:26873577

  8. Codon Bias Patterns of E. coli’s Interacting Proteins

    PubMed Central

    Dilucca, Maddalena; Cimini, Giulio; Semmoloni, Andrea; Deiana, Antonio; Giansanti, Andrea

    2015-01-01

    Synonymous codons, i.e., DNA nucleotide triplets coding for the same amino acid, are used differently across the variety of living organisms. The biological meaning of this phenomenon, known as codon usage bias, is still controversial. In order to shed light on this point, we propose a new codon bias index, CompAI, that is based on the competition between cognate and near-cognate tRNAs during translation, without being tuned to the usage bias of highly expressed genes. We perform a genome-wide evaluation of codon bias for E.coli, comparing CompAI with other widely used indices: tAI, CAI, and Nc. We show that CompAI and tAI capture similar information by being positively correlated with gene conservation, measured by the Evolutionary Retention Index (ERI), and essentiality, whereas, CAI and Nc appear to be less sensitive to evolutionary-functional parameters. Notably, the rate of variation of tAI and CompAI with ERI allows to obtain sets of genes that consistently belong to specific clusters of orthologous genes (COGs). We also investigate the correlation of codon bias at the genomic level with the network features of protein-protein interactions in E.coli. We find that the most densely connected communities of the network share a similar level of codon bias (as measured by CompAI and tAI). Conversely, a small difference in codon bias between two genes is, statistically, a prerequisite for the corresponding proteins to interact. Importantly, among all codon bias indices, CompAI turns out to have the most coherent distribution over the communities of the interactome, pointing to the significance of competition among cognate and near-cognate tRNAs for explaining codon usage adaptation. Notably, CompAI may potentially correlate with translation speed measurements, by accounting for the specific delay induced by wobble-pairing between codons and anticodons. PMID:26566157

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

    PubMed

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

    2012-12-01

    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

  10. Codon and Amino Acid Usage Are Shaped by Selection Across Divergent Model Organisms of the Pancrustacea.

    PubMed

    Whittle, Carrie A; Extavour, Cassandra G

    2015-11-01

    In protein-coding genes, synonymous codon usage and amino acid composition correlate to expression in some eukaryotes, and may result from translational selection. Here, we studied large-scale RNA-seq data from three divergent arthropod models, including cricket (Gryllus bimaculatus), milkweed bug (Oncopeltus fasciatus), and the amphipod crustacean Parhyale hawaiensis, and tested for optimization of codon and amino acid usage relative to expression level. We report strong signals of AT3 optimal codons (those favored in highly expressed genes) in G. bimaculatus and O. fasciatus, whereas weaker signs of GC3 optimal codons were found in P. hawaiensis, suggesting selection on codon usage in all three organisms. Further, in G. bimaculatus and O. fasciatus, high expression was associated with lowered frequency of amino acids with large size/complexity (S/C) scores in favor of those with intermediate S/C values; thus, selection may favor smaller amino acids while retaining those of moderate size for protein stability or conformation. In P. hawaiensis, highly transcribed genes had elevated frequency of amino acids with large and small S/C scores, suggesting a complex dynamic in this crustacean. In all species, the highly transcribed genes appeared to favor short proteins, high optimal codon usage, specific amino acids, and were preferentially involved in cell-cycling and protein synthesis. Together, based on examination of 1,680,067, 1,667,783, and 1,326,896 codon sites in G. bimaculatus, O. fasciatus, and P. hawaiensis, respectively, we conclude that translational selection shapes codon and amino acid usage in these three Pancrustacean arthropods. PMID:26384771

  11. Codon and Amino Acid Usage Are Shaped by Selection Across Divergent Model Organisms of the Pancrustacea

    PubMed Central

    Whittle, Carrie A.; Extavour, Cassandra G.

    2015-01-01

    In protein-coding genes, synonymous codon usage and amino acid composition correlate to expression in some eukaryotes, and may result from translational selection. Here, we studied large-scale RNA-seq data from three divergent arthropod models, including cricket (Gryllus bimaculatus), milkweed bug (Oncopeltus fasciatus), and the amphipod crustacean Parhyale hawaiensis, and tested for optimization of codon and amino acid usage relative to expression level. We report strong signals of AT3 optimal codons (those favored in highly expressed genes) in G. bimaculatus and O. fasciatus, whereas weaker signs of GC3 optimal codons were found in P. hawaiensis, suggesting selection on codon usage in all three organisms. Further, in G. bimaculatus and O. fasciatus, high expression was associated with lowered frequency of amino acids with large size/complexity (S/C) scores in favor of those with intermediate S/C values; thus, selection may favor smaller amino acids while retaining those of moderate size for protein stability or conformation. In P. hawaiensis, highly transcribed genes had elevated frequency of amino acids with large and small S/C scores, suggesting a complex dynamic in this crustacean. In all species, the highly transcribed genes appeared to favor short proteins, high optimal codon usage, specific amino acids, and were preferentially involved in cell-cycling and protein synthesis. Together, based on examination of 1,680,067, 1,667,783, and 1,326,896 codon sites in G. bimaculatus, O. fasciatus, and P. hawaiensis, respectively, we conclude that translational selection shapes codon and amino acid usage in these three Pancrustacean arthropods. PMID:26384771

  12. Codon usage biases of transposable elements and host nuclear genes in Arabidopsis thaliana and Oryza sativa.

    PubMed

    Jia, Jia; Xue, Qingzhong

    2009-12-01

    Transposable elements (TEs) are mobile genetic entities ubiquitously distributed in nearly all genomes. High frequency of codons ending in A/T in TEs has been previously observed in some species. In this study, the biases in nucleotide composition and codon usage of TE transposases and host nuclear genes were investigated in the AT-rich genome of Arabidopsis thaliana and the GC-rich genome of Oryza sativa. Codons ending in A/T are more frequently used by TEs compared with their host nuclear genes. A remarkable positive correlation between highly expressed nuclear genes and C/G-ending codons were detected in O. sativa (r=0.944 and 0.839, respectively, P<0.0001) but not in A. thaliana, indicating a close association between the GC content and gene expression level in monocot species. In both species, TE codon usage biases are similar to that of weakly expressed genes. The expression and activity of TEs may be strictly controlled in plant genomes. Mutation bias and selection pressure have simultaneously acted on the TE evolution in A. thaliana and O. sativa. The consistently observed biases of nucleotide composition and codon usage of TEs may also provide a useful clue to accurately detect TE sequences in different species. PMID:20172490

  13. Evidence for Stabilizing Selection on Codon Usage in Chromosomal Rearrangements of Drosophila pseudoobscura

    PubMed Central

    Fuller, Zachary L.; Haynes, Gwilym D.; Zhu, Dianhui; Batterton, Matthew; Chao, Hsu; Dugan, Shannon; Javaid, Mehwish; Jayaseelan, Joy C.; Lee, Sandra; Li, Mingmei; Ongeri, Fiona; Qi, Sulan; Han, Yi; Doddapaneni, Harshavardhan; Richards, Stephen; Schaeffer, Stephen W.

    2014-01-01

    There has been a renewed interest in investigating the role of stabilizing selection acting on genome-wide traits such as codon usage bias. Codon bias, when synonymous codons are used at unequal frequencies, occurs in a wide variety of taxa. Standard evolutionary models explain the maintenance of codon bias through a balance of genetic drift, mutation and weak purifying selection. The efficacy of selection is expected to be reduced in regions of suppressed recombination. Contrary to observations in Drosophila melanogaster, some recent studies have failed to detect a relationship between the recombination rate, intensity of selection acting at synonymous sites, and the magnitude of codon bias as predicted under these standard models. Here, we examined codon bias in 2798 protein coding loci on the third chromosome of D. pseudoobscura using whole-genome sequences of 47 individuals, representing five common third chromosome gene arrangements. Fine-scale recombination maps were constructed using more than 1 million segregating sites. As expected, recombination was demonstrated to be significantly suppressed between chromosome arrangements, allowing for a direct examination of the relationship between recombination, selection, and codon bias. As with other Drosophila species, we observe a strong mutational bias away from the most frequently used codons. We find the rate of synonymous and nonsynonymous polymorphism is variable between different amino acids. However, we do not observe a reduction in codon bias or the strength of selection in regions of suppressed recombination as expected. Instead, we find that the interaction between weak stabilizing selection and mutational bias likely plays a role in shaping the composition of synonymous codons across the third chromosome in D. pseudoobscura. PMID:25326424

  14. Coevolution between Stop Codon Usage and Release Factors in Bacterial Species.

    PubMed

    Wei, Yulong; Wang, Juan; Xia, Xuhua

    2016-09-01

    Three stop codons in bacteria represent different translation termination signals, and their usage is expected to depend on their differences in translation termination efficiency, mutation bias, and relative abundance of release factors (RF1 decoding UAA and UAG, and RF2 decoding UAA and UGA). In 14 bacterial species (covering Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria and Spirochetes) with cellular RF1 and RF2 quantified, UAA is consistently over-represented in highly expressed genes (HEGs) relative to lowly expressed genes (LEGs), whereas UGA usage is the opposite even in species where RF2 is far more abundant than RF1. UGA usage relative to UAG increases significantly with PRF2 [=RF2/(RF1 + RF2)] as expected from adaptation between stop codons and their decoders. PRF2 is > 0.5 over a wide range of AT content (measured by PAT3 as the proportion of AT at third codon sites), but decreases rapidly toward zero at the high range of PAT3 This explains why bacterial lineages with high PAT3 often have UGA reassigned because of low RF2. There is no indication that UAG is a minor stop codon in bacteria as claimed in a recent publication. The claim is invalid because of the failure to apply the two key criteria in identifying a minor codon: (1) it is least preferred by HEGs (or most preferred by LEGs) and (2) it corresponds to the least abundant decoder. Our results suggest a more plausible explanation for why UAA usage increases, and UGA usage decreases, with PAT3, but UAG usage remains low over the entire PAT3 range. PMID:27297468

  15. Coevolution between Stop Codon Usage and Release Factors in Bacterial Species

    PubMed Central

    Wei, Yulong; Wang, Juan; Xia, Xuhua

    2016-01-01

    Three stop codons in bacteria represent different translation termination signals, and their usage is expected to depend on their differences in translation termination efficiency, mutation bias, and relative abundance of release factors (RF1 decoding UAA and UAG, and RF2 decoding UAA and UGA). In 14 bacterial species (covering Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria and Spirochetes) with cellular RF1 and RF2 quantified, UAA is consistently over-represented in highly expressed genes (HEGs) relative to lowly expressed genes (LEGs), whereas UGA usage is the opposite even in species where RF2 is far more abundant than RF1. UGA usage relative to UAG increases significantly with PRF2 [=RF2/(RF1 + RF2)] as expected from adaptation between stop codons and their decoders. PRF2 is > 0.5 over a wide range of AT content (measured by PAT3 as the proportion of AT at third codon sites), but decreases rapidly toward zero at the high range of PAT3. This explains why bacterial lineages with high PAT3 often have UGA reassigned because of low RF2. There is no indication that UAG is a minor stop codon in bacteria as claimed in a recent publication. The claim is invalid because of the failure to apply the two key criteria in identifying a minor codon: (1) it is least preferred by HEGs (or most preferred by LEGs) and (2) it corresponds to the least abundant decoder. Our results suggest a more plausible explanation for why UAA usage increases, and UGA usage decreases, with PAT3, but UAG usage remains low over the entire PAT3 range. PMID:27297468

  16. Pangenome Evidence for Higher Codon Usage Bias and Stronger Translational Selection in Core Genes of Escherichia coli

    PubMed Central

    Sun, Shixiang; Xiao, Jingfa; Zhang, Huiyong; Zhang, Zhang

    2016-01-01

    Codon usage bias, as a combined interplay from mutation and selection, has been intensively studied in Escherichia coli. However, codon usage analysis in an E. coli pangenome remains unexplored and the relative importance of mutation and selection acting on core genes and strain-specific genes is unknown. Here we perform comprehensive codon usage analyses based on a collection of multiple complete genome sequences of E. coli. Our results show that core genes that are present in all strains have higher codon usage bias than strain-specific genes that are unique to single strains. We further explore the forces in influencing codon usage and investigate the difference of the major force between core and strain-specific genes. Our results demonstrate that although mutation may exert genome-wide influences on codon usage acting similarly in different gene sets, selection dominates as an important force to shape biased codon usage as genes are present in an increased number of strains. Together, our results provide important insights for better understanding genome plasticity and complexity as well as evolutionary mechanisms behind codon usage bias. PMID:27536275

  17. Pangenome Evidence for Higher Codon Usage Bias and Stronger Translational Selection in Core Genes of Escherichia coli.

    PubMed

    Sun, Shixiang; Xiao, Jingfa; Zhang, Huiyong; Zhang, Zhang

    2016-01-01

    Codon usage bias, as a combined interplay from mutation and selection, has been intensively studied in Escherichia coli. However, codon usage analysis in an E. coli pangenome remains unexplored and the relative importance of mutation and selection acting on core genes and strain-specific genes is unknown. Here we perform comprehensive codon usage analyses based on a collection of multiple complete genome sequences of E. coli. Our results show that core genes that are present in all strains have higher codon usage bias than strain-specific genes that are unique to single strains. We further explore the forces in influencing codon usage and investigate the difference of the major force between core and strain-specific genes. Our results demonstrate that although mutation may exert genome-wide influences on codon usage acting similarly in different gene sets, selection dominates as an important force to shape biased codon usage as genes are present in an increased number of strains. Together, our results provide important insights for better understanding genome plasticity and complexity as well as evolutionary mechanisms behind codon usage bias. PMID:27536275

  18. Synonymous Codon Usage Affects the Expression of Wild Type and F508del CFTR

    PubMed Central

    Shah, Kalpit; Cheng, Yi; Hahn, Brian; Bridges, Robert; Bradbury, Neil; Mueller, David M.

    2015-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel composed of 1480 amino acids. The major mutation responsible for cystic fibrosis results in loss of amino acid residue, F508, (F508del). Loss of F508 in CFTR alters the folding pathway resulting in endoplasmic reticulum associated degradation (ERAD). This study investigates the role of synonymous codon in the expression of CFTR and CFTR F508del in human HEK293 cells. DNA encoding the open reading frame (ORF) for CFTR containing synonymous codon replacements, were expressed using a heterologous vector integrated into the genome. The results indicate that the codon usage greatly affects the expression of CFTR. While the promoter strength driving expression of the ORFs was largely unchanged and the mRNA half-lives were unchanged, the steady state levels of the mRNA varied by as much as 30 fold. Experiments support that this apparent inconsistency is attributed to exon junction complex independent nonsense mediated decay. The ratio of CFTR/mRNA indicates that mRNA containing native codons was more efficient in expressing mature CFTR as compared to mRNA containing synonymous high expression codons. However, when F508del CFTR was expressed after codon optimization, a greater percentage of the protein escaped ERAD resulting in considerable levels of mature F508del CFTR on the plasma membrane, which showed channel activity. These results indicate that for CFTR, codon usage has an effect on mRNA levels, protein expression and likely, for F508del CFTR, chaperone assisted folding pathway. PMID:25676312

  19. Effective population size does not predict codon usage bias in mammals.

    PubMed

    Kessler, Michael D; Dean, Matthew D

    2014-10-01

    Synonymous codons are not used at equal frequency throughout the genome, a phenomenon termed codon usage bias (CUB). It is often assumed that interspecific variation in the intensity of CUB is related to species differences in effective population sizes (N e), with selection on CUB operating less efficiently in species with small N e. Here, we specifically ask whether variation in N e predicts differences in CUB in mammals and report two main findings. First, across 41 mammalian genomes, CUB was not correlated with two indirect proxies of N e (body mass and generation time), even though there was statistically significant evidence of selection shaping CUB across all species. Interestingly, autosomal genes showed higher codon usage bias compared to X-linked genes, and high-recombination genes showed higher codon usage bias compared to low recombination genes, suggesting intraspecific variation in N e predicts variation in CUB. Second, across six mammalian species with genetic estimates of N e (human, chimpanzee, rabbit, and three mouse species: Mus musculus, M. domesticus, and M. castaneus), N e and CUB were weakly and inconsistently correlated. At least in mammals, interspecific divergence in N e does not strongly predict variation in CUB. One hypothesis is that each species responds to a unique distribution of selection coefficients, confounding any straightforward link between N e and CUB. PMID:25505518

  20. Effective population size does not predict codon usage bias in mammals

    PubMed Central

    Kessler, Michael D; Dean, Matthew D

    2014-01-01

    Synonymous codons are not used at equal frequency throughout the genome, a phenomenon termed codon usage bias (CUB). It is often assumed that interspecific variation in the intensity of CUB is related to species differences in effective population sizes (Ne), with selection on CUB operating less efficiently in species with small Ne. Here, we specifically ask whether variation in Ne predicts differences in CUB in mammals and report two main findings. First, across 41 mammalian genomes, CUB was not correlated with two indirect proxies of Ne (body mass and generation time), even though there was statistically significant evidence of selection shaping CUB across all species. Interestingly, autosomal genes showed higher codon usage bias compared to X-linked genes, and high-recombination genes showed higher codon usage bias compared to low recombination genes, suggesting intraspecific variation in Ne predicts variation in CUB. Second, across six mammalian species with genetic estimates of Ne (human, chimpanzee, rabbit, and three mouse species: Mus musculus, M. domesticus, and M. castaneus), Ne and CUB were weakly and inconsistently correlated. At least in mammals, interspecific divergence in Ne does not strongly predict variation in CUB. One hypothesis is that each species responds to a unique distribution of selection coefficients, confounding any straightforward link between Ne and CUB. PMID:25505518

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

    PubMed Central

    Morton, B R

    2001-01-01

    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. PMID:11560910

  2. Synonymous Codon Usage Bias in Plant Mitochondrial Genes Is Associated with Intron Number and Mirrors Species Evolution

    PubMed Central

    Zhao, Mingming; Yin, Xunhao; Xia, Guangmin; Wang, Mengcheng

    2015-01-01

    Synonymous codon usage bias (SCUB) is a common event that a non-uniform usage of codons often occurs in nearly all organisms. We previously found that SCUB is correlated with both intron number and exon position in the plant nuclear genome but not in the plastid genome; SCUB in both nuclear and plastid genome can mirror the evolutionary specialization. However, how about the rules in the mitochondrial genome has not been addressed. Here, we present an analysis of SCUB in the mitochondrial genome, based on 24 plant species ranging from algae to land plants. The frequencies of NNA and NNT (A- and T-ending codons) are higher than those of NNG and NNC, with the strongest preference in bryophytes and the weakest in land plants, suggesting an association between SCUB and plant evolution. The preference for NNA and NNT is more evident in genes harboring a greater number of introns in land plants, but the bias to NNA and NNT exhibits even among exons. The pattern of SCUB in the mitochondrial genome differs in some respects to that present in both the nuclear and plastid genomes. PMID:26110418

  3. Big Data, Evolution, and Metagenomes: Predicting Disease from Gut Microbiota Codon Usage Profiles.

    PubMed

    Fabijanić, Maja; Vlahoviček, Kristian

    2016-01-01

    Metagenomics projects use next-generation sequencing to unravel genetic potential in microbial communities from a wealth of environmental niches, including those associated with human body and relevant to human health. In order to understand large datasets collected in metagenomics surveys and interpret them in context of how a community metabolism as a whole adapts and interacts with the environment, it is necessary to extend beyond the conventional approaches of decomposing metagenomes into microbial species' constituents and performing analysis on separate components. By applying concepts of translational optimization through codon usage adaptation on entire metagenomic datasets, we demonstrate that a bias in codon usage present throughout the entire microbial community can be used as a powerful analytical tool to predict for community lifestyle-specific metabolism. Here we demonstrate this approach combined with machine learning, to classify human gut microbiome samples according to the pathological condition diagnosed in the human host. PMID:27115650

  4. Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses

    PubMed Central

    Félez-Sánchez, Marta; Trösemeier, Jan-Hendrik; Bedhomme, Stéphanie; González-Bravo, Maria Isabel; Kamp, Christel; Bravo, Ignacio G.

    2015-01-01

    Viruses rely completely on the hosts’ machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response. PMID:26139833

  5. Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses.

    PubMed

    Félez-Sánchez, Marta; Trösemeier, Jan-Hendrik; Bedhomme, Stéphanie; González-Bravo, Maria Isabel; Kamp, Christel; Bravo, Ignacio G

    2015-08-01

    Viruses rely completely on the hosts' machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response. PMID:26139833

  6. Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels

    PubMed Central

    Frenkel-Morgenstern, Milana; Danon, Tamar; Christian, Thomas; Igarashi, Takao; Cohen, Lydia; Hou, Ya-Ming; Jensen, Lars Juhl

    2012-01-01

    The cell cycle is a temporal program that regulates DNA synthesis and cell division. When we compared the codon usage of cell cycle-regulated genes with that of other genes, we discovered that there is a significant preference for non-optimal codons. Moreover, genes encoding proteins that cycle at the protein level exhibit non-optimal codon preferences. Remarkably, cell cycle-regulated genes expressed in different phases display different codon preferences. Here, we show empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase of the cell cycle, consistent with the non-optimal codon usage of genes expressed at this time, and lowest toward the end of G1, reflecting the optimal codon usage of G1 genes. Accordingly, protein levels of human glycyl-, threonyl-, and glutamyl-prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase. In light of our findings, we propose that non-optimal (wobbly) matching codons influence protein synthesis during the cell cycle. We describe a new mathematical model that shows how codon usage can give rise to cell-cycle regulation. In summary, our data indicate that cells exploit wobbling to generate cell cycle-dependent dynamics of proteins. PMID:22373820

  7. Predicting Gene Expression Level from Relative Codon Usage Bias: An Application to Escherichia coli Genome

    PubMed Central

    Roymondal, Uttam; Das, Shibsankar; Sahoo, Satyabrata

    2009-01-01

    We present an expression measure of a gene, devised to predict the level of gene expression from relative codon bias (RCB). There are a number of measures currently in use that quantify codon usage in genes. Based on the hypothesis that gene expressivity and codon composition is strongly correlated, RCB has been defined to provide an intuitively meaningful measure of an extent of the codon preference in a gene. We outline a simple approach to assess the strength of RCB (RCBS) in genes as a guide to their likely expression levels and illustrate this with an analysis of Escherichia coli (E. coli) genome. Our efforts to quantitatively predict gene expression levels in E. coli met with a high level of success. Surprisingly, we observe a strong correlation between RCBS and protein length indicating natural selection in favour of the shorter genes to be expressed at higher level. The agreement of our result with high protein abundances, microarray data and radioactive data demonstrates that the genomic expression profile available in our method can be applied in a meaningful way to the study of cell physiology and also for more detailed studies of particular genes of interest. PMID:19131380

  8. Codon Usage and 3' UTR Length Determine Maternal mRNA Stability in Zebrafish.

    PubMed

    Mishima, Yuichiro; Tomari, Yukihide

    2016-03-17

    The control of mRNA stability plays a central role in regulating gene expression. In metazoans, the earliest stages of development are driven by maternally supplied mRNAs. The degradation of these maternal mRNAs is critical for promoting the maternal-to-zygotic transition of developmental programs, although the underlying mechanisms are poorly understood in vertebrates. Here, we characterized maternal mRNA degradation pathways in zebrafish using a transcriptome analysis and systematic reporter assays. Our data demonstrate that ORFs enriched with uncommon codons promote deadenylation by the CCR4-NOT complex in a translation-dependent manner. This codon-mediated mRNA decay is conditional on the context of the 3' UTR, with long 3' UTRs conferring resistance to deadenylation. These results indicate that the combined effect of codon usage and 3' UTR length determines the stability of maternal mRNAs in zebrafish embryos. Our study thus highlights the codon-mediated mRNA decay as a conserved regulatory mechanism in eukaryotes. PMID:26990990

  9. JCat: a novel tool to adapt codon usage of a target gene to its potential expression host.

    PubMed

    Grote, Andreas; Hiller, Karsten; Scheer, Maurice; Münch, Richard; Nörtemann, Bernd; Hempel, Dietmar C; Jahn, Dieter

    2005-07-01

    A novel method for the adaptation of target gene codon usage to most sequenced prokaryotes and selected eukaryotic gene expression hosts was developed to improve heterologous protein production. In contrast to existing tools, JCat (Java Codon Adaptation Tool) does not require the manual definition of highly expressed genes and is, therefore, a very rapid and easy method. Further options of JCat for codon adaptation include the avoidance of unwanted cleavage sites for restriction enzymes and Rho-independent transcription terminators. The output of JCat is both graphically and as Codon Adaptation Index (CAI) values given for the pasted sequence and the newly adapted sequence. Additionally, a list of genes in FASTA-format can be uploaded to calculate CAI values. In one example, all genes of the genome of Caenorhabditis elegans were adapted to Escherichia coli codon usage and further optimized to avoid commonly used restriction sites. In a second example, the Pseudomonas aeruginosa exbD gene codon usage was adapted to E.coli codon usage with parallel avoidance of the same restriction sites. For both, the degree of introduced changes was documented and evaluated. JCat is integrated into the PRODORIC database that hosts all required information on the various organisms to fulfill the requested calculations. JCat is freely accessible at http://www.prodoric.de/JCat. PMID:15980527

  10. Equine schlafen 11 restricts the production of equine infectious anemia virus via a codon usage-dependent mechanism.

    PubMed

    Lin, Yue-Zhi; Sun, Liu-Ke; Zhu, Dan-Tong; Hu, Zhe; Wang, Xue-Feng; Du, Cheng; Wang, Yu-Hong; Wang, Xiao-Jun; Zhou, Jian-Hua

    2016-08-01

    Human schlafen11 is a novel restriction factor for HIV-1 based on bias regarding relative synonymous codon usage (RSCU). Here, we report the cloning of equine schlafen11 (eSLFN11) and the characteristics of its role in restricting the production of equine infectious anemia virus (EIAV), a retrovirus similar to HIV-1. Overexpression of eSLFN11 inhibited EIAV replication, whereas knockdown of endogenous eSLFN11 by siRNA enhanced the release of EIAV from its principal target cell. Notably, although eSLFN11 significantly suppressed expression of viral Gag protein and EIAV release into the culture medium, the levels of intracellular viral early gene proteins Tat and Rev and viral genomic RNA were unaffected. Coincidently, similar altered patterns of codon usage bias were observed for both the early and late genes of EIAV. Therefore, our data suggest that eSLFN11 restricts EIAV production by impairing viral mRNA translation via a mechanism that is similar to that employed by hSLFN11 for HIV-1. PMID:27200480

  11. Analysis of phylogeny and codon usage bias and relationship of GC content, amino acid composition with expression of the structural nif genes.

    PubMed

    Mondal, Sunil Kanti; Kundu, Sudip; Das, Rabindranath; Roy, Sujit

    2016-08-01

    Bacteria and archaea have evolved with the ability to fix atmospheric dinitrogen in the form of ammonia, catalyzed by the nitrogenase enzyme complex which comprises three structural genes nifK, nifD and nifH. The nifK and nifD encodes for the beta and alpha subunits, respectively, of component 1, while nifH encodes for component 2 of nitrogenase. Phylogeny based on nifDHK have indicated that Cyanobacteria is closer to Proteobacteria alpha and gamma but not supported by the tree based on 16SrRNA. The evolutionary ancestor for the different trees was also different. The GC1 and GC2% analysis showed more consistency than GC3% which appeared to below for Firmicutes, Cyanobacteria and Euarchaeota while highest in Proteobacteria beta and clearly showed the proportional effect on the codon usage with a few exceptions. Few genes from Firmicutes, Euryarchaeota, Proteobacteria alpha and delta were found under mutational pressure. These nif genes with low and high GC3% from different classes of organisms showed similar expected number of codons. Distribution of the genes and codons, based on codon usage demonstrated opposite pattern for different orientation of mirror plane when compared with each other. Overall our results provide a comprehensive analysis on the evolutionary relationship of the three structural nif genes, nifK, nifD and nifH, respectively, in the context of codon usage bias, GC content relationship and amino acid composition of the encoded proteins and exploration of crucial statistical method for the analysis of positive data with non-constant variance to identify the shape factors of codon adaptation index. PMID:26309237

  12. Ribosome collisions and translation efficiency: optimization by codon usage and mRNA destabilization.

    PubMed

    Mitarai, Namiko; Sneppen, Kim; Pedersen, Steen

    2008-09-26

    Individual mRNAs are translated by multiple ribosomes that initiate translation with an interval of a few seconds. The ribosome speed is codon dependent, and ribosome queuing has been suggested to explain specific data for translation of some mRNAs in vivo. By modeling the stochastic translation process as a traffic problem, we here analyze conditions and consequences of collisions and queuing. The model allowed us to determine the on-rate (0.8 to 1.1 initiations/s) and the time (1 s) the preceding ribosome occludes initiation for Escherichia coli lacZ mRNA in vivo. We find that ribosome collisions and queues are inevitable consequences of a stochastic translation mechanism that reduce the translation efficiency substantially on natural mRNAs. The cells minimize collisions by having its mRNAs being unstable and by a highly selected codon usage in the start of the mRNA. The cost of mRNA breakdown is offset by the concomitant increase in translation efficiency. PMID:18619977

  13. Use of molecular beacons to probe for messenger RNA release from ribosomes during 5'-translational blockage by consecutive low-usage codons in Escherichia coli

    NASA Astrophysics Data System (ADS)

    Gao, Wenwu; Tyagi, Sanjay; Kramer, Fred R.; Goldman, Emanuel

    2000-03-01

    In `5'-translational blockage,' significantly reduced yields of proteins are synthesized in Escherichia coli when consecutive low-usage codons are inserted near translation starts of messages (with reduced or no effect when these same codons are inserted downstream). We tested the hypothesis that ribosomes encountering these low-usage codons prematurely release the mRNA. RNA from polysome gradients was fractionated into pools of polysomes, monosomes and ribosomes-free. New hybridization probes, called `molecular beacons,' and standard slot-blots, were used to detect test messages containing either consecutive low-usage AGG (arginine) or synonymous high-usage CGU insertions near the 5' end. The results show an approximately twofold increase in the ratio of free to bound mRNA when the low-usage codons were present compared to high-usage codons. In contrast, there was no difference in the ratio of free to bound mRNA when consecutive low-usage CUA or high-usage CUG (leucine) codons were inserted, or when the arginine codons were inserted near the 3' end. These data indicate that at least some mRNA is released from ribosomes during 5'-translational blockage by arginine but not leucine codons, and they support proposals that premature termination of translation can occur in some conditions in vivo in the absence of a stop codon.

  14. Recurrent positive selection and heterogeneous codon usage bias events leading to coexistence of divergent pigeon circoviruses.

    PubMed

    Liao, Pei-Chun; Wang, Kung-Kai; Tsai, Shinn-Shyong; Liu, Hung-Jen; Huang, Bing-Hong; Chuang, Kuo-Pin

    2015-08-01

    The capsid genes from 14 pigeon circovirus (PiCV) sequences, collected from Taiwan between 2009 and 2010, were sequenced and compared with 14 PiCV capsid gene sequences from GenBank. Based on pairwise comparison, PiCV strains from Taiwan shared 73.9-100% nucleotide identity and 72-100% amino acid identity with those of the 14 reported PiCV sequences. Phylogenetic analyses revealed that Taiwanese PiCV isolates can be grouped into two clades: clade 1 comprising isolates from Belgium, Australia, USA, Italy and China, and clade 2 showing close relation to isolates from Germany and France. Recurrent positive selection was detected in clade 1 PiCV lineages, which may contribute to the diversification of predominant PiCV sequences in Taiwan. Further observations suggest that synonymous codon usage variations between PiCV clade 1 and clade 2 may reflect the adaptive divergence on translation efficiency of capsid genes in infectious hosts. Variation in selective pressures acting on the evolutionary divergence and codon usage bias of both clades explains the regional coexistence of virus sequences congeners prevented from competitive exclusion within an island such as Taiwan. Our genotyping results also provide insight into the aetiological agents of PiCV outbreak in Taiwan and we present a comparative analysis of the central coding region of PiCV genome. From the sequence comparison results of 28 PiCVs which differs in regard to the geographical origin and columbid species, we identified conserved regions within the capsid gene that are likely to be suitable for primer selection and vaccine development. PMID:25911731

  15. Enhanced production of recombinant Mycobacterium tuberculosis antigens in Escherichia coli by replacement of low-usage codons.

    PubMed

    Lakey, D L; Voladri, R K; Edwards, K M; Hager, C; Samten, B; Wallis, R S; Barnes, P F; Kernodle, D S

    2000-01-01

    A major obstacle to development of subunit vaccines and diagnostic reagents for tuberculosis is the inability to produce large quantities of these proteins. To test the hypothesis that poor expression of some mycobacterial genes in Escherichia coli is due, in part, to the presence of low-usage E. coli codons, we used site-directed mutagenesis to convert low-usage codons to high-usage codons for the same amino acid in the Mycobacterium tuberculosis genes for antigens 85A and 85B and superoxide dismutase. Replacement of five codons in the wild-type gene for antigen 85B increased recombinant protein production in E. coli 54-fold. The recombinant antigen elicited proliferation and gamma interferon production by lymphocytes from healthy tuberculin reactors and was recognized by monoclonal antibodies to native antigen 85, indicating that the recombinant antigen contained T-cell and B-cell epitopes. Northern blotting demonstrated only a 1.7- to 2.5-fold increase in antigen 85B mRNA, suggesting that the enhanced protein production was due primarily to enhanced efficiency of translation. Codon replacement in the genes encoding antigen 85A and superoxide dismutase yielded four- to sixfold increases in recombinant protein production, suggesting that this strategy may be generally applicable to overexpression of mycobacterial genes in E. coli. PMID:10603393

  16. Downregulating viral gene expression: codon usage bias manipulation for the generation of novel influenza A virus vaccines

    PubMed Central

    Baker, Steven F; Nogales, Aitor; Martínez-Sobrido, Luis

    2015-01-01

    Vaccination represents the best option to protect humans against influenza virus. However, improving the effectiveness of current vaccines could better stifle the health burden caused by viral infection. Protein synthesis from individual genes can be downregulated by synthetically deoptimizing a gene’s codon usage. With more rapid and affordable nucleotide synthesis, generating viruses that contain genes with deoptimized codons is now feasible. Attenuated, vaccine-candidate viruses can thus be engineered with hitherto uncharacterized properties. With eight gene segments, influenza A viruses with variably recoded genomes can produce a spectrum of attenuation that is contingent on the gene segment targeted and the number of codon changes. This review summarizes different targets and approaches to deoptimize influenza A virus codons for novel vaccine generation. PMID:26213563

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

    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 of its position in the genome. We show that the cumulative density of bases in bacterial genomes can be separated into an average (or secular) plus a fluctuating part. Bacterial genomes can be divided into two groups according to the qualitative description of their secular part: linear and piecewise linear. These two groups of genomes show different properties when their nucleotide spacing distribution is studied. In order to analyze genomes having a variable nucleotide density, statistically, the use of unfolding is necessary, i.e., to get a separation between the secular part and the fluctuations. The unfolding allows an adequate comparison with the statistical properties of other genomes. With this methodology, four genomes were analyzed Burkholderia, Bacillus, Clostridium and Corynebacterium. Interestingly, the nearest neighbor spacing distributions or detrended distance distributions are very similar for species within the same genus but they are very different for species from different genera. This difference can be attributed to the difference in the codon usage.

  18. Understanding Road Usage Patterns in Urban Areas

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    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.

  19. Usage of the three termination codons in a single eukaryotic cell, the Xenopus laevis oocyte.

    PubMed Central

    Bienz, M; Kubli, E; Kohli, J; deHenau, S; Huez, G; Marbaix, G; Grosjean, H

    1981-01-01

    Oocytes from Xenopus laevis were injected with purified amber (UAG), ochre (UAA), and opal (UGA) suppressor tRNAs from yeasts. The radioactively labeled proteins translated from the endogenous mRNAs were then separated on two-dimensional gels. All three termination codons are used in a single cell, the Xenopus laevis oocyte. But a surprisingly low number of readthrough polypeptides were observed from the 600 mRNAs studied in comparison to uninjected oocytes. The experimental data are compared with the conclusions obtained from the compilation of all available termination sequences on eukaryotic and prokaryotic mRNAs. This comparison indicates that the apparent resistance of natural termination codons against readthrough, as observed by the microinjection experiments, cannot be explained by tandem or very close second stop codons. Instead it suggests that specific context sequences around the termination codons may play a role in the efficiency of translation termination. Images PMID:7024919

  20. Synonymous Codon Usage Bias in the Plastid Genome is Unrelated to Gene Structure and Shows Evolutionary Heterogeneity

    PubMed Central

    Qi, Yueying; Xu, Wenjing; Xing, Tian; Zhao, Mingming; Li, Nana; Yan, Li; Xia, Guangmin; Wang, Mengcheng

    2015-01-01

    Synonymous codon usage bias (SCUB) is the nonuniform usage of codons, occurring often in nearly all organisms. Our previous study found that SCUB is correlated with intron number, is unequal among exons in the plant nuclear genome, and mirrors evolutionary specialization. However, whether this rule exists in the plastid genome has not been addressed. Here, we present an analysis of SCUB in the plastid genomes of 25 species from lower to higher plants (algae, bryophytes, pteridophytes, gymnosperms, and spermatophytes). We found NNA and NNT (A- and T-ending codons) are preferential in the plastid genomes of all plants. Interestingly, this preference is heterogeneous among taxonomies of plants, with the strongest preference in bryophytes and the weakest in pteridophytes, suggesting an association between SCUB and plant evolution. In addition, SCUB frequencies are consistent among genes with varied introns and among exons, indicating that the bias of NNA and NNT is unrelated to either intron number or exon position. Further, SCUB is associated with DNA methylation–induced conversion of cytosine to thymine in the vascular plants but not in algae or bryophytes. These data demonstrate that these SCUB profiles in the plastid genome are distinctly different compared with the nuclear genome. PMID:25922569

  1. Quantitative Effect of Suboptimal Codon Usage on Translational Efficiency of mRNA Encoding HIV-1 gag in Intact T Cells

    PubMed Central

    Ngumbela, Kholiswa C.; Ryan, Kieran P.; Sivamurthy, Rohini; Brockman, Mark A.; Gandhi, Rajesh T.; Bhardwaj, Nina; Kavanagh, Daniel G.

    2008-01-01

    Background The sequences of wild-isolate strains of Human Immunodeficiency Virus-1 (HIV-1) are characterized by low GC content and suboptimal codon usage. Codon optimization of DNA vectors can enhance protein expression both by enhancing translational efficiency, and by altering RNA stability and export. Although gag codon optimization is widely used in DNA vectors and experimental vaccines, the actual effect of altered codon usage on gag translational efficiency has not been quantified. Methodology and Principal Findings To quantify translational efficiency of gag mRNA in live T cells, we transfected Jurkat cells with increasing doses of capped, polyadenylated synthetic mRNA corresponding to wildtype or codon-optimized gag sequences, measured Gag production by quantitative ELISA and flow cytometry, and estimated the translational efficiency of each transcript as pg of Gag antigen produced per µg of input mRNA. We found that codon optimization yielded a small increase in gag translational efficiency (approximately 1.6 fold). In contrast when cells were transfected with DNA vectors requiring nuclear transcription and processing of gag mRNA, codon optimization resulted in a very large enhancement of Gag production. Conclusions We conclude that suboptimal codon usage by HIV-1 results in only a slight loss of gag translational efficiency per se, with the vast majority of enhancement in protein expression from DNA vectors due to altered processing and export of nuclear RNA. PMID:18523584

  2. Usage Patterns of Open Genomic Data

    ERIC Educational Resources Information Center

    Xia, Jingfeng; Liu, Ying

    2013-01-01

    This paper uses Genome Expression Omnibus (GEO), a data repository in biomedical sciences, to examine the usage patterns of open data repositories. It attempts to identify the degree of recognition of data reuse value and understand how e-science has impacted a large-scale scholarship. By analyzing a list of 1,211 publications that cite GEO data…

  3. Usage Patterns of an Online Search System.

    ERIC Educational Resources Information Center

    Cooper, Michael D.

    1983-01-01

    Examines usage patterns of ELHILL retrieval program of National Library of Medicine's MEDLARS system. Based on sample of 6,759 searches, the study analyzes frequency of various commands, classifies messages issued by system, and investigates searcher error rates. Suggestions for redesigning program and query language are noted. Seven references…

  4. Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses

    PubMed Central

    Pavesi, Angelo; Magiorkinis, Gkikas; Karlin, David G.

    2013-01-01

    A well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes, e.g. by duplication or horizontal transfer. In contrast, many viruses generate protein-coding genes de novo, via the overprinting of a new reading frame onto an existing (“ancestral”) frame. This mechanism is thought to play an important role in viral pathogenicity, but has been poorly explored, perhaps because identifying the de novo frames is very challenging. Therefore, a new approach to detect them was needed. We assembled a reference set of overlapping genes for which we could reliably determine the ancestral frames, and found that their codon usage was significantly closer to that of the rest of the viral genome than the codon usage of de novo frames. Based on this observation, we designed a method that allowed the identification of de novo frames based on their codon usage with a very good specificity, but intermediate sensitivity. Using our method, we predicted that the Rex gene of deltaretroviruses has originated de novo by overprinting the Tax gene. Intriguingly, several genes in the same genomic region have also originated de novo and encode proteins that regulate the functions of Tax. Such “gene nurseries” may be common in viral genomes. Finally, our results confirm that the genomic GC content is not the only determinant of codon usage in viruses and suggest that a constraint linked to translation must influence codon usage. PMID:23966842

  5. Codon usage determines the mutational robustness, evolutionary capacity and virulence of an RNA virus

    PubMed Central

    Lauring, Adam S.; Acevedo, Ashley; Cooper, Samantha B.; Andino, Raul

    2012-01-01

    Summary RNA viruses exist as dynamic and diverse populations shaped by constant mutation and selection. Yet little is known about how the mutant spectrum contributes to virus evolvability and pathogenesis. Because several codon choices are available for a given amino acid, a central question concerns whether viral sequences have evolved to optimize not only the protein coding consensus, but also the DNA/RNA sequences accessible through mutation. Here we directly test this hypothesis by comparing wild type poliovirus to synthetic viruses carrying reengineered capsid sequences with hundreds of synonymous mutations. Strikingly, such rewiring of the population's mutant network reduced its robustness and attenuated the virus in an animal model of infection. We conclude that the position of a virus in sequence space defines its mutant spectrum, evolutionary trajectory, and pathogenicity. This organizing principle for RNA virus populations confers tolerance to mutations and facilitates replication and spread within the dynamic host environment. PMID:23159052

  6. Classification of Arabidopsis thaliana gene sequences: clustering of coding sequences into two groups according to codon usage improves gene prediction.

    PubMed

    Mathé, C; Peresetsky, A; Déhais, P; Van Montagu, M; Rouzé, P

    1999-02-01

    While genomic sequences are accumulating, finding the location of the genes remains a major issue that can be solved only for about a half of them by homology searches. Prediction methods are thus required, but unfortunately are not fully satisfying. Most prediction methods implicitly assume a unique model for genes. This is an oversimplification as demonstrated by the possibility to group coding sequences into several classes in Escherichia coli and other genomes. As no classification existed for Arabidopsis thaliana, we classified genes according to the statistical features of their coding sequences. A clustering algorithm using a codon usage model was developed and applied to coding sequences from A. thaliana, E. coli, and a mixture of both. By using it, Arabidopsis sequences were clustered into two classes. The CU1 and CU2 classes differed essentially by the choice of pyrimidine bases at the codon silent sites: CU2 genes often use C whereas CU1 genes prefer T. This classification discriminated the Arabidopsis genes according to their expressiveness, highly expressed genes being clustered in CU2 and genes expected to have a lower expression, such as the regulatory genes, in CU1. The algorithm separated the sequences of the Escherichia-Arabidopsis mixed data set into five classes according to the species, except for one class. This mixed class contained 89 % Arabidopsis genes from CU1 and 11 % E. coli genes, mostly horizontally transferred. Interestingly, most genes encoding organelle-targeted proteins, except the photosynthetic and photoassimilatory ones, were clustered in CU1. By tailoring the GeneMark CDS prediction algorithm to the observed coding sequence classes, its quality of prediction was greatly improved. Similar improvement can be expected with other prediction systems. PMID:9925779

  7. Mitochondrial phylogenomics of early land plants: mitigating the effects of saturation, compositional heterogeneity, and codon-usage bias.

    PubMed

    Liu, Yang; Cox, Cymon J; Wang, Wei; Goffinet, Bernard

    2014-11-01

    Phylogenetic analyses using concatenation of genomic-scale data have been seen as the panacea for resolving the incongruences among inferences from few or single genes. However, phylogenomics may also suffer from systematic errors, due to the, perhaps cumulative, effects of saturation, among-taxa compositional (GC content) heterogeneity, or codon-usage bias plaguing the individual nucleotide loci that are concatenated. Here, we provide an example of how these factors affect the inferences of the phylogeny of early land plants based on mitochondrial genomic data. Mitochondrial sequences evolve slowly in plants and hence are thought to be suitable for resolving deep relationships. We newly assembled mitochondrial genomes from 20 bryophytes, complemented these with 40 other streptophytes (land plants plus algal outgroups), compiling a data matrix of 60 taxa and 41 mitochondrial genes. Homogeneous analyses of the concatenated nucleotide data resolve mosses as sister-group to the remaining land plants. However, the corresponding translated amino acid data support the liverwort lineage in this position. Both results receive weak to moderate support in maximum-likelihood analyses, but strong support in Bayesian inferences. Tests of alternative hypotheses using either nucleotide or amino acid data provide implicit support for their respective optimal topologies, and clearly reject the hypotheses that bryophytes are monophyletic, liverworts and mosses share a unique common ancestor, or hornworts are sister to the remaining land plants. We determined that land plant lineages differ in their nucleotide composition, and in their usage of synonymous codon variants. Composition heterogeneous Bayesian analyses employing a nonstationary model that accounts for variation in among-lineage composition, and inferences from degenerated nucleotide data that avoid the effects of synonymous substitutions that underlie codon-usage bias, again recovered liverworts being sister to the

  8. Over expression of a synthetic gene encoding interferon lambda using relative synonymous codon usage bias in Escherichia coli.

    PubMed

    Akhtar, Hashaam; Akhtar, Samar; Jan, Syed Umer; Khan, Azka; Zaidi, Najam us Sahar Sadaf; Qadri, Ishtiaq

    2013-11-01

    Interferon Lambda (IFN-λ) is a type III interferon which belongs to a novel family of cytokines and possesses antiviral and antitumor properties. It is unique in its own class of cytokines; because of the specificity towards its heterodimer receptors and its structural similarities with cytokines of other classes. This renders IFN-λ a better choice for the treatment against many diseases including viral hepatitis and human coronavirus (HCoV-EMC). The present study describes a computational approach known as relative synonymous codon usage (RSCU); used to enhance the expression of IFN-λ protein in a eukaryotic expression system. Manually designed and commercially synthesized IFN-λ gene was cloned into pET-22b expression plasmid under the control of inducible T7-lac promoter. Maximum levels of IFN-λ expression was observed with 0.4 mM IPTG in transformed E. coli incubated for 4 hours in LB medium. Higher concentrations of IPTG had no or negative effect on the expression of IFN-λ. This synthetically over expressed IFN-λ can be tested as a targeted treatment option for viral hepatitis after purification. PMID:24191324

  9. Hepatitis A Virus Adaptation to Cellular Shutoff Is Driven by Dynamic Adjustments of Codon Usage and Results in the Selection of Populations with Altered Capsids

    PubMed Central

    Costafreda, M. Isabel; Pérez-Rodriguez, Francisco J.; D'Andrea, Lucía; Guix, Susana; Ribes, Enric; Bosch, Albert

    2014-01-01

    ABSTRACT Hepatitis A virus (HAV) has a highly biased and deoptimized codon usage compared to the host cell and fails to inhibit host protein synthesis. It has been proposed that an optimal combination of abundant and rare codons controls the translation speed required for the correct capsid folding. The artificial shutoff host protein synthesis results in the selection of variants containing mutations in the HAV capsid coding region critical for folding, stability, and function. Here, we show that these capsid mutations resulted in changes in their antigenicity; in a reduced stability to high temperature, low pH, and biliary salts; and in an increased efficacy of cell entry. In conclusion, the adaptation to cellular shutoff resulted in the selection of large-plaque-producing virus populations. IMPORTANCE HAV has a naturally deoptimized codon usage with respect to that of its cell host and is unable to shut down the cellular translation. This fact contributes to the low replication rate of the virus, in addition to other factors such as the highly inefficient internal ribosome entry site (IRES), and explains the outstanding physical stability of this pathogen in the environment mediated by a folding-dependent highly cohesive capsid. Adaptation to artificially induced cellular transcription shutoff resulted in a redeoptimization of its capsid codon usage, instead of an optimization. These genomic changes are related to an overall change of capsid folding, which in turn induces changes in the cell entry process. Remarkably, the adaptation to cellular shutoff allowed the virus to significantly increase its RNA uncoating efficiency, resulting in the selection of large-plaque-producing populations. However, these populations produced much-debilitated virions. PMID:24554668

  10. Changing the Codon Usage of hfq Gene has Profound Effect on Phenotype and Pathogenicity of Salmonella Typhimurium.

    PubMed

    Behera, Parthasarathi; Kutty, V H Muhammed; Kumar, Ajeet; Sharma, Bhaskar

    2016-03-01

    Genome recoding with bias codons (synonymous rare codons) or codon pair bias is being used as a method to attenuate virulence mostly in viruses. The target gene chosen for attenuation in general in bacteria is mostly toxin or virulence gene. We have used RNA chaperone hfq, a global post-transcriptional regulator of bacterial gene expression that regulates about 20 % genes in Salmonella, as the target of recoding. The hfq gene was recoded by replacing the codons of hfq gene with synonymous rare codons. Recoding decreased the expression of Hfq protein about two-fold in the mutant as compared to the parent strain. Recoding did not affect growth kinetics, but in growth competition the mutant strain was outcompeted by the parent strain. There was significant decrease in survivability of mutant strain in macrophage as compared to the parent strain. The biofilm formation was significantly impaired in case of recoded mutant. The mutants were also less motile as compared to the parent strain. Intraperitoneal infection of mice with the mutant strain had shown better survival as compared to parent strain. The results show that recoding is an effective method of reducing virulence. PMID:26620536

  11. Gene Expression Levels Are Correlated with Synonymous Codon Usage, Amino Acid Composition, and Gene Architecture in the Red Flour Beetle, Tribolium castaneum

    PubMed Central

    Williford, Anna; Demuth, Jeffery P.

    2012-01-01

    Gene expression levels correlate with multiple aspects of gene sequence and gene structure in phylogenetically diverse taxa, suggesting an important role of gene expression levels in the evolution of protein-coding genes. Here we present results of a genome-wide study of the influence of gene expression on synonymous codon usage, amino acid composition, and gene structure in the red flour beetle, Tribolium castaneum. Consistent with the action of translational selection, we find that synonymous codon usage bias increases with gene expression. However, the correspondence between tRNA gene copy number and optimal codons is weak. At the amino acid level, translational selection is suggested by the positive correlation between tRNA gene numbers and amino acid usage, which is stronger for highly expressed genes. In addition, there is a clear trend for increased use of metabolically cheaper, less complex amino acids as gene expression increases. tRNA gene numbers also correlate negatively with amino acid size/complexity (S/C) score indicating the coupling between translational selection and selection to minimize the use of large/complex amino acids. Interestingly, the analysis of 10 additional genomes suggests that the correlation between tRNA gene numbers and amino acid S/C score is widespread and might be explained by selection against negative consequences of protein misfolding. At the level of gene structure, three major trends are detected: 1) complete coding region length increases across low and intermediate expression levels but decreases in highly expressed genes; 2) the average intron size shows the opposite trend, first decreasing with expression, followed by a slight increase in highly expressed genes; and 3) intron density remains nearly constant across all expression levels. These changes in gene architecture are only in partial agreement with selection favoring reduced cost of biosynthesis. PMID:22826459

  12. Web Usage, Advertising, and Shopping: Relationship Patterns.

    ERIC Educational Resources Information Center

    Korgaonkar, Pradeep; Wolin, Lori D.

    2002-01-01

    Discusses Web sales and explores the differences between heavy, medium, and light Web users in terms of their beliefs about Web advertising, attitudes toward Web advertising, purchasing patterns, and demographics. Suggests marketers need to target Web advertising to particular Web users. (Author/LRW)

  13. Investigating Learner Preparedness for and Usage Patterns of Mobile Learning

    ERIC Educational Resources Information Center

    Stockwell, Glenn

    2008-01-01

    While the use of mobile devices for language learning has sparked the interest of an increasing number of researchers in recent years (e.g., Aizawa & Kiernan, 2003; Thornton & Houser, 2005), our knowledge of learners' preferences for the mobile platform and their usage patterns remains limited. Are learners prepared to use mobile phones for…

  14. Mobile usage and sleep patterns among medical students.

    PubMed

    Yogesh, Saxena; Abha, Shrivastava; Priyanka, Singh

    2014-01-01

    Exposure of humans to radio frequency electromagnetic field (EMF) both during receiving and transmitting the signals has amplified public and scientific debate about possible adverse effects on human health. The study was designed with the objective of assessing the extent of mobile phone use amongst medical students and finding correlation if any between the hours of usage of mobile to sleep pattern and quality. hundred medical students grouped as cases (n = 57) (> 2 hours/day of mobile usage) and control (n = 43) (≤ 2 hours/day of mobile usage) were examined for their sleep quality & pattern by Pittsburg sleep Quality Index (PSQI). Differences between groups were examined with the Mann Whitney "U" test for proportions (Quantitative values) and with Student't' test for continuous variables. The association of variables was analyzed by Spearman Rank's correlation. Probability was set at < 0.05 as significant. Sleep disturbance, latency and day dysfunction was more in cases especially females. A significant association of hours of usage and sleep indices were observed in both genders (males r = 0.25; p = 0.04, females r = 0.31; p = 0.009). Evening usage of mobile phone in cases showed a statistically significant negative association (-0.606; p = 0.042) with Sleep quality (higher PSQI means sleep deprivation). Students using mobile for > 2 hours/day may cause sleep deprivation and day sleepiness affecting cognitive and learning abilities of medical students. PMID:25464686

  15. Mobile usage and sleep patterns among medical students.

    PubMed

    Yogesh, Saxena; Abha, Shrivastava; Priyanka, Singh

    2014-01-01

    Exposure of humans to radio frequency electromagnetic field (EMF) both during receiving and transmitting the signals has amplified public and scientific debate about possible adverse effects on human health. The study was designed with the objective of assessing the extent of mobile phone use amongst medical students and finding correlation if any between the hours of usage of mobile to sleep pattern and quality. hundred medical students grouped as cases (n = 57) (> 2 hours/day of mobile usage) and control (n = 43) (≤ 2 hours/day of mobile usage) were examined for their sleep quality & pattern by Pittsburg sleep Quality Index (PSQI). Differences between groups were examined with the Mann Whitney "U" test for proportions (Quantitative values) and with Student't' test for continuous variables. The association of variables was analyzed by Spearman Rank's correlation. Probability was set at < 0.05 as significant. Sleep disturbance, latency and day dysfunction was more in cases especially females. A significant association of hours of usage and sleep indices were observed in both genders (males r = 0.25; p = 0.04, females r = 0.31; p = 0.009). Evening usage of mobile phone in cases showed a statistically significant negative association (-0.606; p = 0.042) with Sleep quality (higher PSQI means sleep deprivation). Students using mobile for > 2 hours/day may cause sleep deprivation and day sleepiness affecting cognitive and learning abilities of medical students. PMID:25508317

  16. High-level accumulation of recombinant miraculin protein in transgenic tomatoes expressing a synthetic miraculin gene with optimized codon usage terminated by the native miraculin terminator.

    PubMed

    Hiwasa-Tanase, Kyoko; Nyarubona, Mpanja; Hirai, Tadayoshi; Kato, Kazuhisa; Ichikawa, Takanari; Ezura, Hiroshi

    2011-01-01

    In our previous study, a transgenic tomato line that expressed the MIR gene under control of the cauliflower mosaic virus 35S promoter and the nopaline synthase terminator (tNOS) produced the taste-modifying protein miraculin (MIR). However, the concentration of MIR in the tomatoes was lower than that in the MIR gene's native miracle fruit. To increase MIR production, the native MIR terminator (tMIR) was used and a synthetic gene encoding MIR protein (sMIR) was designed to optimize its codon usage for tomato. Four different combinations of these genes and terminators (MIR-tNOS, MIR-tMIR, sMIR-tNOS and sMIR-tMIR) were constructed and used for transformation. The average MIR concentrations in MIR-tNOS, MIR-tMIR, sMIR-tNOS and sMIR-tMIR fruits were 131, 197, 128 and 287 μg/g fresh weight, respectively. The MIR concentrations using tMIR were higher than those using tNOS. The highest MIR accumulation was detected in sMIR-tMIR fruits. On the other hand, the MIR concentration was largely unaffected by sMIR-tNOS. The expression levels of both MIR and sMIR mRNAs terminated by tMIR tended to be higher than those terminated by tNOS. Read-through mRNA transcripts terminated by tNOS were much longer than those terminated by tMIR. These results suggest that tMIR enhances mRNA expression and permits the multiplier effect of optimized codon usage. PMID:21076835

  17. Migraine prophylactic medication usage patterns in The Netherlands.

    PubMed

    Rahimtoola, H; Buurma, H; Tijssen, C C; Leufkens, H G; Egberts, A C G

    2003-05-01

    This study aims to investigate usage patterns of specific migraine prophylactic medications in ergotamine and triptan patients commencing this treatment for the first time during 1 January 1992 until 31 December 1998. Usage patterns of specific migraine prophylactic drugs were evaluated for each patient by accessing data from a large prescription database and were characterized as continued, switch or stop use during the patient observation period. Several patient and medication-related factors were explored in order to identify a possible relationship with the specific usage pattern defined. Approximately 75% of the study population (n = 729) had terminated (stop or switch) prophylactic treatment after 1 year. Age < 40 years (relative risk (RR) 1.9; 95% confidence interval (CI) 1.2-3.2) and the concomitant use of non-steroidal anti-inflammatory drugs (RR 3.2; 95% CI 1.2-5.5) or specific abortive migraine drugs resulted in a faster onset of treatment modification (switch). Overall, migraine prophylactic treatment is used for a relatively short period, probably attributable to the common limitations associated with migraine prophylaxis, such as poor compliance and/or limited therapeutic efficacy. Patterns of use can be influenced by a variety of factors, including age, type of prescriber and certain co-medication. Patient interview studies are required to clarify these issues further. PMID:12716348

  18. Usage pattern of personal care products in California households.

    PubMed

    Wu, Xiangmei May; Bennett, Deborah H; Ritz, Beate; Cassady, Diana L; Lee, Kiyoung; Hertz-Picciotto, Irva

    2010-11-01

    Given the concern over the potential for health risks associated with certain ingredients (e.g., phthalates) in personal care products, usage patterns of ∼30 types of personal care products (e.g., shampoo, sunscreen, fragrance, etc.) were collected in 604 California households through a telephone interview. Preferences in selecting products, e.g., scented or unscented, aerosol, and brand loyalty, were also investigated. Participants were recruited in three age groups, children (mostly preschoolers), their parents, and adults age 55 or older. Use frequencies of various product types varied by sex, age group, race, education, and climatic region. Product use by parent and child from the same household were correlated. Use frequencies of products in the same class (e.g., skincare) were moderately correlated, which may impact aggregate exposures. Use frequencies observed in this study were generally in the same range as those reported in the EPA Exposure Factor Handbook, but we found differences for some individual products. Our study provides additional data on population-based usage patterns of a large collection of commonly used personal care products pertaining to several age groups and socio-demographic strata. This information will be valuable for exposure and risk assessments. PMID:20696198

  19. Multi-omics data driven analysis establishes reference codon biases for synthetic gene design in microbial and mammalian cells.

    PubMed

    Ang, Kok Siong; Kyriakopoulos, Sarantos; Li, Wei; Lee, Dong-Yup

    2016-06-01

    In this study, we analyzed multi-omics data and subsets thereof to establish reference codon usage biases for codon optimization in synthetic gene design. Specifically, publicly available genomic, transcriptomic, proteomic and translatomic data for microbial and mammalian expression hosts, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris and Chinese hamster ovary (CHO) cells, were compiled to derive their individual codon and codon pair frequencies. Then, host dependent and -omics specific codon biases were generated and compared by principal component analysis and hierarchical clustering. Interestingly, our results indicated the similar codon bias patterns of the highly expressed transcripts, highly abundant proteins, and efficiently translated mRNA in microbial cells, despite the general lack of correlation between mRNA and protein expression levels. However, for CHO cells, the codon bias patterns among various -omics subsets are not distinguishable, forming one cluster. Thus, we further investigated the effect of different input codon biases on codon optimized sequences using the codon context (CC) and individual codon usage (ICU) design parameters, via in silico case study on the expression of human IFNγ sequence in CHO cells. The results supported that CC is more robust design parameter than ICU for improved heterologous gene design. PMID:26850284

  20. Codon Adaptation of Plastid Genes.

    PubMed

    Suzuki, Haruo; Morton, Brian R

    2016-01-01

    Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes. PMID:27196606

  1. Codon Adaptation of Plastid Genes

    PubMed Central

    Suzuki, Haruo; Morton, Brian R.

    2016-01-01

    Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes. PMID:27196606

  2. The Rare Codon AGA Is Involved in Regulation of Pyoluteorin Biosynthesis in Pseudomonas protegens Pf-5.

    PubMed

    Yan, Qing; Philmus, Benjamin; Hesse, Cedar; Kohen, Max; Chang, Jeff H; Loper, Joyce E

    2016-01-01

    The soil bacterium Pseudomonas protegens Pf-5 can colonize root and seed surfaces of many plants, protecting them from infection by plant pathogenic fungi and oomycetes. The capacity to suppress disease is attributed to Pf-5's production of a large spectrum of antibiotics, which is controlled by complex regulatory circuits operating at the transcriptional and post-transcriptional levels. In this study, we analyzed the genomic sequence of Pf-5 for codon usage patterns and observed that the six rarest codons in the genome are present in all seven known antibiotic biosynthesis gene clusters. In particular, there is an abundance of rare codons in pltR, which encodes a member of the LysR transcriptional regulator family that controls the expression of pyoluteorin biosynthetic genes. To test the hypothesis that rare codons in pltR influence pyoluteorin production, we generated a derivative of Pf-5 in which 23 types of rare codons in pltR were substituted with synonymous preferred codons. The resultant mutant produced pyoluteorin at levels 15 times higher than that of the wild-type Pf-5. Accordingly, the promoter activity of the pyoluteorin biosynthetic gene pltL was 20 times higher in the codon-modified stain than in the wild-type. pltR has six AGA codons, which is the rarest codon in the Pf-5 genome. Substitution of all six AGA codons with preferred Arg codons resulted in a variant of pltR that conferred increased pyoluteorin production and pltL promoter activity. Furthermore, overexpression of tRNA[Formula: see text], the cognate tRNA for the AGA codon, significantly increased pyoluteorin production by Pf-5. A bias in codon usage has been linked to the regulation of many phenotypes in eukaryotes and prokaryotes but, to our knowledge, this is the first example of the role of a rare codon in the regulation of antibiotic production by a Gram-negative bacterium. PMID:27148187

  3. The Rare Codon AGA Is Involved in Regulation of Pyoluteorin Biosynthesis in Pseudomonas protegens Pf-5

    PubMed Central

    Yan, Qing; Philmus, Benjamin; Hesse, Cedar; Kohen, Max; Chang, Jeff H.; Loper, Joyce E.

    2016-01-01

    The soil bacterium Pseudomonas protegens Pf-5 can colonize root and seed surfaces of many plants, protecting them from infection by plant pathogenic fungi and oomycetes. The capacity to suppress disease is attributed to Pf-5's production of a large spectrum of antibiotics, which is controlled by complex regulatory circuits operating at the transcriptional and post-transcriptional levels. In this study, we analyzed the genomic sequence of Pf-5 for codon usage patterns and observed that the six rarest codons in the genome are present in all seven known antibiotic biosynthesis gene clusters. In particular, there is an abundance of rare codons in pltR, which encodes a member of the LysR transcriptional regulator family that controls the expression of pyoluteorin biosynthetic genes. To test the hypothesis that rare codons in pltR influence pyoluteorin production, we generated a derivative of Pf-5 in which 23 types of rare codons in pltR were substituted with synonymous preferred codons. The resultant mutant produced pyoluteorin at levels 15 times higher than that of the wild-type Pf-5. Accordingly, the promoter activity of the pyoluteorin biosynthetic gene pltL was 20 times higher in the codon-modified stain than in the wild-type. pltR has six AGA codons, which is the rarest codon in the Pf-5 genome. Substitution of all six AGA codons with preferred Arg codons resulted in a variant of pltR that conferred increased pyoluteorin production and pltL promoter activity. Furthermore, overexpression of tRNAUCUArg, the cognate tRNA for the AGA codon, significantly increased pyoluteorin production by Pf-5. A bias in codon usage has been linked to the regulation of many phenotypes in eukaryotes and prokaryotes but, to our knowledge, this is the first example of the role of a rare codon in the regulation of antibiotic production by a Gram-negative bacterium. PMID:27148187

  4. Enhanced expression of codon optimized interferon gamma in CHO cells.

    PubMed

    Chung, Bevan Kai-Sheng; Yusufi, Faraaz N K; Mariati; Yang, Yuansheng; Lee, Dong-Yup

    2013-09-10

    The human interferon-gamma (IFN-γ) is a potential drug candidate for treating various diseases due to its immunomodulatory properties. The efficient production of this protein can be achieved through a popular industrial host, Chinese hamster ovary (CHO) cells. However, recombinant expression of foreign proteins is typically suboptimal possibly due to the usage of non-native codon patterns within the coding sequence. Therefore, we demonstrated the application of a recently developed codon optimization approach to design synthetic IFN-γ coding sequences for enhanced heterologous expression in CHO cells. For codon optimization, earlier studies suggested to establish the target usage distribution pattern in terms of selected design parameters such as individual codon usage (ICU) and codon context (CC), mainly based on the host's highly expressed genes. However, our RNA-Seq based transcriptome profiling indicated that the ICU and CC distribution patterns of different gene expression classes in CHO cell are relatively similar, unlike other microbial expression hosts, Escherichia coli and Saccharomyces cerevisiae. This finding was further corroborated through the in vivo expression of various ICU and CC optimized IFN-γ in CHO cells. Interestingly, the CC-optimized genes exhibited at least 13-fold increase in expression level compared to the wild-type IFN-γ while a maximum of 10-fold increase was observed for the ICU-optimized genes. Although design criteria based on individual codons, such as ICU, have been widely used for gene optimization, our experimental results suggested that codon context is relatively more effective parameter for improving recombinant IFN-γ expression in CHO cells. PMID:23876479

  5. Translation attenuation via 3' terminal codon usage in bovine csn1s2 is responsible for the difference in αs2- and β-casein profile in milk.

    PubMed

    Kim, Julie J; Yu, Jaeju; Bag, Jnanankur; Bakovic, Marica; Cant, John P

    2015-01-01

    The rate of secretion of αs2-casein into bovine milk is approximately 25% of that of β-casein, yet mammary expression of their respective mRNA transcripts (csn1s2 and csn2) is not different. Our objective was to identify molecular mechanisms that explain the difference in translation efficiency between csn1s2 and csn2. Cell-free translational efficiency of csn2 was 5 times that of csn1s2. Transcripts of csn1s2 distributed into heavier polysomes than csn2 transcripts, indicating an attenuation of elongation and/or termination. Stimulatory and inhibitory effects of the 5' and 3' UTRs on translational efficiency were different with luciferase and casein sequences in the coding regions. Substituting the 5' and 3' UTRs from csn2 into csn1s2 did not improve csn1s2 translation, implicating the coding region itself in the translation difference. Deletion of a 28-codon fragment from the 3' terminus of the csn1s2 coding region, which displays codons with low correlations to cell fitness, increased translation to a par with csn2. We conclude that the usage of the last 28 codons of csn1s2 is the main regulatory element that attenuates its expression and is responsible for the differential translational expression of csn1s2 and csn2. PMID:25826667

  6. Translation attenuation via 3′ terminal codon usage in bovine csn1s2 is responsible for the difference in αs2- and β-casein profile in milk

    PubMed Central

    Kim, Julie J; Yu, Jaeju; Bag, Jnanankur; Bakovic, Marica; Cant, John P

    2015-01-01

    The rate of secretion of αs2-casein into bovine milk is approximately 25% of that of β-casein, yet mammary expression of their respective mRNA transcripts (csn1s2 and csn2) is not different. Our objective was to identify molecular mechanisms that explain the difference in translation efficiency between csn1s2 and csn2. Cell-free translational efficiency of csn2 was 5 times that of csn1s2. Transcripts of csn1s2 distributed into heavier polysomes than csn2 transcripts, indicating an attenuation of elongation and/or termination. Stimulatory and inhibitory effects of the 5′ and 3′ UTRs on translational efficiency were different with luciferase and casein sequences in the coding regions. Substituting the 5′ and 3′ UTRs from csn2 into csn1s2 did not improve csn1s2 translation, implicating the coding region itself in the translation difference. Deletion of a 28-codon fragment from the 3′ terminus of the csn1s2 coding region, which displays codons with low correlations to cell fitness, increased translation to a par with csn2. We conclude that the usage of the last 28 codons of csn1s2 is the main regulatory element that attenuates its expression and is responsible for the differential translational expression of csn1s2 and csn2. PMID:25826667

  7. Student Media Usage Patterns and Non-Traditional Learning in Higher Education

    ERIC Educational Resources Information Center

    Zawacki-Richter, Olaf; Müskens, Wolfgang; Krause, Ulrike; Alturki, Uthman; Aldraiweesh, Ahmed

    2015-01-01

    A total of 2,338 students at German universities participated in a survey, which investigated media usage patterns of so-called traditional and non-traditional students (Schuetze & Wolter, 2003). The students provided information on the digital devices that they own or have access to, and on their usage of media and e-learning tools and…

  8. Long memory in patterns of mobile phone usage

    NASA Astrophysics Data System (ADS)

    Owczarczuk, Marcin

    2012-02-01

    In this article we show that usage of a mobile phone, i.e. daily series of number of calls made by a customer, exhibits long memory. We use a sample of 4502 postpaid users from a Polish mobile operator and study their two-year billing history. We estimate Hurst exponent by nine estimators: aggregated variance method, differencing the variance, absolute values of the aggregated series, Higuchi's method, residuals of regression, the R/S method, periodogram method, modified periodogram method and Whittle estimator. We also analyze empirically relations between estimators. Long memory implies an inertial effect in clients' behavior which may be used by mobile operators to accelerate usage and gain additional profit.

  9. Assessing usage patterns of electronic clinical documentation templates.

    PubMed

    Vawdrey, David K

    2008-01-01

    Many vendors of electronic medical records support structured and free-text entry of clinical documents using configurable templates. At a healthcare institution comprising two large academic medical centers, a documentation management data mart and a custom, Web-accessible business intelligence application were developed to track the availability and usage of electronic documentation templates. For each medical center, template availability and usage trends were measured from November 2007 through February 2008. By February 2008, approximately 65,000 electronic notes were authored per week on the two campuses. One site had 934 available templates, with 313 being used to author at least one note. The other site had 765 templates, of which 480 were used. The most commonly used template at both campuses was a free text note called "Miscellaneous Nursing Note," which accounted for 33.3% of total documents generated at one campus and 15.2% at the other. PMID:18998863

  10. Prevalent Accumulation of Non-Optimal Codons through Somatic Mutations in Human Cancers

    PubMed Central

    Wu, Xudong; Li, Guohui

    2016-01-01

    Cancer is characterized by uncontrolled cell growth, and the cause of different cancers is generally attributed to checkpoint dysregulation of cell proliferation and apoptosis. Recent studies have shown that non-optimal codons were preferentially adopted by genes to generate cell cycle-dependent oscillations in protein levels. This raises the intriguing question of how dynamic changes of codon usage modulate the cancer genome to cope with a non-controlled proliferative cell cycle. In this study, we comprehensively analyzed the somatic mutations of codons in human cancers, and found that non-optimal codons tended to be accumulated through both synonymous and non-synonymous mutations compared with other types of genomic substitution. We further demonstrated that non-optimal codons were prevalently accumulated across different types of cancers, amino acids, and chromosomes, and genes with accumulation of non-optimal codons tended to be involved in protein interaction/signaling networks and encoded important enzymes in metabolic networks that played roles in cancer-related pathways. This study provides insights into the dynamics of codons in the cancer genome and demonstrates that accumulation of non-optimal codons may be an adaptive strategy for cancerous cells to win the competition with normal cells. This deeper interpretation of the patterns and the functional characterization of somatic mutations of codons will help to broaden the current understanding of the molecular basis of cancers. PMID:27513638

  11. Quantifying Wikipedia Usage Patterns Before Stock Market Moves

    NASA Astrophysics Data System (ADS)

    Moat, Helen Susannah; Curme, Chester; Avakian, Adam; Kenett, Dror Y.; Stanley, H. Eugene; Preis, Tobias

    2013-05-01

    Financial crises result from a catastrophic combination of actions. Vast stock market datasets offer us a window into some of the actions that have led to these crises. Here, we investigate whether data generated through Internet usage contain traces of attempts to gather information before trading decisions were taken. We present evidence in line with the intriguing suggestion that data on changes in how often financially related Wikipedia pages were viewed may have contained early signs of stock market moves. Our results suggest that online data may allow us to gain new insight into early information gathering stages of decision making.

  12. Phylogenetic Patterns of Codon Evolution in the ACTIN-DEPOLYMERIZING FACTOR/COFILIN (ADF/CFL) Gene Family

    PubMed Central

    Roy-Zokan, Eileen M.; Dyer, Kelly A.; Meagher, Richard B.

    2015-01-01

    The actin-depolymerizing factor/cofilin (ADF/CFL) gene family encodes a diverse group of relatively small proteins. Once known strictly as modulators of actin filament dynamics, recent research has demonstrated that these proteins are involved in a variety of cellular processes, from signal transduction to the cytonuclear trafficking of actin. In both plant and animal lineages, expression patterns of paralogs in the ADF/CFL gene family vary among tissue types and developmental stages. In this study we use computational approaches to investigate the evolutionary forces responsible for the diversification of the ADF/CFL gene family. Estimating the rate of non-synonymous to synonymous mutations (dN/dS) across phylogenetic lineages revealed that the majority of ADF/CFL codon positions were under strong purifying selection, with rare episodic events of accelerated protein evolution. In both plants and animals these instances of accelerated evolution were ADF/CFL subclass specific, and all of the sites under selection were located in regions of the protein that could serve in new functional roles. We suggest these sites may have been important in the functional diversification of ADF/CFL proteins. PMID:26717562

  13. An initial log analysis of usage patterns on a research networking system.

    PubMed

    Boland, Mary Regina; Trembowelski, Sylvia; Bakken, Suzanne; Weng, Chunhua

    2012-08-01

    Usage data for research networking systems (RNSs) are valuable but generally unavailable for understanding scientific professionals' information needs and online collaborator seeking behaviors. This study contributes a method for evaluating RNSs and initial usage knowledge of one RNS obtained from using this method. We designed a log for an institutional RNS, defined categories of users and tasks, and analyzed correlations between usage patterns and user and query types. Our results show that scientific professionals spend more time performing deep Web searching on RNSs than generic Google users and we also show that retrieving scientist profiles is faster on an RNS than on Google (3.5 seconds vs. 34.2 seconds) whereas organization-specific browsing on a RNS takes longer than on Google (117.0 seconds vs. 34.2 seconds). Usage patterns vary by user role, e.g., faculty performed more informational queries than administrators, which implies role-specific user support is needed for RNSs. PMID:22883612

  14. Genome-Wide Analysis Reveals Diverged Patterns of Codon Bias, Gene Expression, and Rates of Sequence Evolution in Picea Gene Families

    PubMed Central

    De La Torre, Amanda R.; Lin, Yao-Cheng; Van de Peer, Yves; Ingvarsson, Pär K.

    2015-01-01

    The recent sequencing of several gymnosperm genomes has greatly facilitated studying the evolution of their genes and gene families. In this study, we examine the evidence for expression-mediated selection in the first two fully sequenced representatives of the gymnosperm plant clade (Picea abies and Picea glauca). We use genome-wide estimates of gene expression (>50,000 expressed genes) to study the relationship between gene expression, codon bias, rates of sequence divergence, protein length, and gene duplication. We found that gene expression is correlated with rates of sequence divergence and codon bias, suggesting that natural selection is acting on Picea protein-coding genes for translational efficiency. Gene expression, rates of sequence divergence, and codon bias are correlated with the size of gene families, with large multicopy gene families having, on average, a lower expression level and breadth, lower codon bias, and higher rates of sequence divergence than single-copy gene families. Tissue-specific patterns of gene expression were more common in large gene families with large gene expression divergence than in single-copy families. Recent family expansions combined with large gene expression variation in paralogs and increased rates of sequence evolution suggest that some Picea gene families are rapidly evolving to cope with biotic and abiotic stress. Our study highlights the importance of gene expression and natural selection in shaping the evolution of protein-coding genes in Picea species, and sets the ground for further studies investigating the evolution of individual gene families in gymnosperms. PMID:25747252

  15. Enabling active and healthy ageing decision support systems with the smart collection of TV usage patterns

    PubMed Central

    Billis, Antonis S.; Batziakas, Asterios; Bratsas, Charalampos; Tsatali, Marianna S.; Karagianni, Maria

    2016-01-01

    Smart monitoring of seniors behavioural patterns and more specifically activities of daily living have attracted immense research interest in recent years. Development of smart decision support systems to support the promotion of health smart homes has also emerged taking advantage of the plethora of smart, inexpensive and unobtrusive monitoring sensors, devices and software tools. To this end, a smart monitoring system has been used in order to extract meaningful information about television (TV) usage patterns and subsequently associate them with clinical findings of experts. The smart TV operating state remote monitoring system was installed in four elderly women homes and gathered data for more than 11 months. Results suggest that TV daily usage (time the TV is turned on) can predict mental health change. Conclusively, the authors suggest that collection of smart device usage patterns could strengthen the inference capabilities of existing health DSSs applied in uncontrolled settings such as real senior homes. PMID:27284457

  16. Temporal Patterns and Dynamics of E-Learning Usage in Medical Education

    ERIC Educational Resources Information Center

    Panzarasa, Pietro; Kujawski, Bernard; Hammond, Edward J.; Roberts, C. Michael

    2016-01-01

    Despite the increasing popularity of e-learning systems across a variety of educational programmes, there is relatively little understanding of how students and trainees distribute their learning efforts over time. This study aimed to analyse the usage patterns of an e-learning resource designed to support specialty training. Data were collected…

  17. Using Compositional Writing Samples to Explore Student Usage Patterns in a Learning Management System

    ERIC Educational Resources Information Center

    Kokensparger, Brian Jay

    2013-01-01

    This study explored relationships between writing sample features and LMS usage patterns for 366 college students who enrolled in Theology courses, junior-level courses cross-listed with theology courses, or Senior Perspective Program courses in the fall semester of 2012. These hybrid courses were managed inside the Canvas(TM) learning management…

  18. Use of the "Personal Delivery" System for Assessment of Drug and Alcohol Attitudes and Usage Patterns.

    ERIC Educational Resources Information Center

    Crabtree, J. Michael; Myers, Stanley B.

    Community data concerning drug and alcohol usage patterns was assessed via a unique "personal delivery" system. The system, which can be used for collecting other community data produced a return rate of 45% and was very economical. This system largely overcomes the main drawback of the mailed questionnaire (low return rate) by (1) having…

  19. Student Usage Patterns and Perceptions for Differentiated Lab Exercises in an Undergraduate Programming Course

    ERIC Educational Resources Information Center

    Mok, H. N.

    2012-01-01

    Differentiated instruction in the form of tiered take-home lab exercises was implemented for students of an undergraduate-level programming course. This paper attempts to uncover the perceptions and usage patterns of students toward these new lab exercises using a comprehensive survey. Findings reveal that these tiered exercises are generally very…

  20. Internet Abuse among Teenagers and Its Relations to Internet Usage Patterns and Demographics

    ERIC Educational Resources Information Center

    Gencer, Suzan Lema; Koc, Mustafa

    2012-01-01

    This study focused on exploring Internet abuse among teenagers and its relations to some Internet usage patterns and demographic characteristics in a digitalizing country, Turkey. It was designed as a cross-sectional research on three types of school that differ in their academic performances. The data were collected from 1380 high school students…

  1. Families in a High-Tech Age: Technology Usage Patterns, Work and Family Correlates, and Gender

    ERIC Educational Resources Information Center

    Chesley, Noelle

    2006-01-01

    This study analyzes a couple-level ("N" = 581), longitudinal data set of employees to provide evidence about technology use over time, the factors that predict use, and the potential for a spouse to influence an individual's use. Although longitudinal usage patterns suggest a trend toward adoption and use of e-mail, the Internet, cell phones, and…

  2. Codon-optimized antibiotic resistance gene improves efficiency of transient transformation in Frankia.

    PubMed

    Kucho, Ken-Ichi; Kakoi, Kentaro; Yamaura, Masatoshi; Iwashita, Mari; Abe, Mikiko; Uchiumi, Toshiki

    2013-11-01

    Frankia is a unique actinobacterium having abilities to fix atmospheric dinitrogen and to establish endosymbiosis with trees, but molecular bases underlying these interesting characteristics are poorly understood because of a lack of stable transformation system. Extremely high GC content of Frankia genome (more than 70 percent) can be a hindrance to successful transformation. We generated a synthetic gentamicin resistance gene whose codon usage is optimized to Frankia (fgmR) and evaluated its usefulness as a selection marker using a transient transformation system. Success rate of transient transformation and cell growth in selective culture were significantly increased by use of fgmR instead of a native gentamicin resistance gene, suggesting that codon optimization improved translation efficiency of the marker gene and increased antibiotic resistance. Our result shows that similarity in codon usage pattern is an important factor to be taken into account when exogenous transgenes are expressed in Frankia cells. PMID:24287650

  3. Cellular immunity survey against urinary tract infection using pVAX/fimH cassette with mammalian and wild type codon usage as a DNA vaccine

    PubMed Central

    Bagherpour, Ghasem; Khoramabadi, Nima; Fallah Mehrabadi, Jalil; Mahdavi, Mehdi; Halabian, Raheleh; Amin, Mohsen; Izadi Mobarakeh, Jalal; Einollahi, Behzad

    2014-01-01

    Purpose FimH (the adhesion fragment of type 1 fimbriae) is implicated in uropathogenic Escherichia coli (UPEC) attachment to epithelial cells through interaction with mannose. Recently, some studies have found that UPEC can thrive intracellularly causing recurrent urinary tract infection (UTI). Almost all vaccines have been designed to induce antibodies against UPEC. Yet, the humoral immune response is not potent enough to overcome neither the primary UTI nor recurrent infections. However, DNA vaccines offer the possibility of inducing cell mediated immune responses and may be a promising preventive tool. Materials and Methods In this study, we employed two different open reading frames within mammalian (mam) and wild type (wt) codons of fimH gene. Optimized fragments were cloned in pVAX-1. Expression of the protein in COS-7 was confirmed by western blot analysis after assessing pVAX/fimH(mam) and pVAX/fimH(wt). The constructs were injected to BALB/c mice at plantar surface of feet followed by electroporation. Results The mice immunized with both constructs following booster injection with recombinant FimH showed increased interferon-γ and interleukin-12 responses significantly higher than non-immunized ones (p<0.05). The immunized mice were challenged with UPEC and then the number of bacteria recovered from the immunized mice was compared with the non-immunized ones. Decreased colony count in immunized mice along with cytokine responses confirmed the promising immune response by the DNA vaccines developed in this study. Conclusion In conclusion, DNA vaccines of UPEC proteins may confer some levels of protection which can be improved by multiple constructs or boosters. PMID:25003092

  4. A codon-usage variant in the (GGN){sub n} trinucleotide polymorphism of the androgen receptor gene as an aid in the prenatal diagnosis of ambiguous genitalia due to partial androgen insensitivity

    SciTech Connect

    Lumbroso, R.; Vasiliou, M.; Beitel, L.K.

    1994-09-01

    Exon 1 at the X-linked androgen receptor (AR) locus encodes an N-terminal modulatory domain that contains two large homopolyamino acid tracts: (CAG;glutamine;Gln){sub 11-33} and (GGN;Glycine;Cly){sub 15-27}. Certain AR mutations cause partial androgen insensitivity (PAI) with frank genital ambiguity that may engender appreciable parental anxiety and patient morbidity. If the AR mutation in a PAI family is unknown, the AR`s intragenic trinucleotide repeat polymorphisms may be used for prenatal diagnosis. However, intergenerational instability of repeat-size may be worrisome, particularly when the information alleles differ by only a few repeats. Here, we report the discovery of a codon-usage (silent substitution) variant in the GGN repeat, and describe its use as a source of complementary information for prenatal diagnosis. The standard sense sequence of the (GGN){sub n} tract is (GGT){sub 3} GGG(GGT){sub 2} (GGC){sub 9-21}. On 4 of 27 X chromosomes we noted that the internal GGT sequence was expanded to 3 or 4 repeats. We used an internal (GGT){sub 4} repeat in a total (GGN){sub 24} tract together with a (CAG){sub 20} tract to distinguish an X chromosome with a mutant AR allele from another X chromosome, bearing a normal allele, that had an internal (GGT){sub 2} repeat in a total (GGN){sub 23} tract together with a (CAG){sub 21} tract. Subsequently, we found the base change leading to a pathogenic amino acid substitution (M779I) in codon 6 of the mutant AR gene in an affected maternal aunt and the fetus at risk. This confirmed the prenatal diagnosis based on the intragenic trinucleotide repeat polymorphisms, and it strengthened the prediction of external genital ambiguity using our previous experience with M779I in another family.

  5. Predicting Negative Emotions Based on Mobile Phone Usage Patterns: An Exploratory Study

    PubMed Central

    Yang, Pei-Ching; Chang, Chia-Chi; Chiang, Jung-Hsien; Chen, Ying-Yeh

    2016-01-01

    Background Prompt recognition and intervention of negative emotions is crucial for patients with depression. Mobile phones and mobile apps are suitable technologies that can be used to recognize negative emotions and intervene if necessary. Objective Mobile phone usage patterns can be associated with concurrent emotional states. The objective of this study is to adapt machine-learning methods to analyze such patterns for the prediction of negative emotion. Methods We developed an Android-based app to capture emotional states and mobile phone usage patterns, which included call logs (and use of apps). Visual analog scales (VASs) were used to report negative emotions in dimensions of depression, anxiety, and stress. In the system-training phase, participants were requested to tag their emotions for 14 consecutive days. Five feature-selection methods were used to determine individual usage patterns and four machine-learning methods were tested. Finally, rank product scoring was used to select the best combination to construct the prediction model. In the system evaluation phase, participants were then requested to verify the predicted negative emotions for at least 5 days. Results Out of 40 enrolled healthy participants, we analyzed data from 28 participants, including 30% (9/28) women with a mean (SD) age of 29.2 (5.1) years with sufficient emotion tags. The combination of time slots of 2 hours, greedy forward selection, and Naïve Bayes method was chosen for the prediction model. We further validated the personalized models in 18 participants who performed at least 5 days of model evaluation. Overall, the predictive accuracy for negative emotions was 86.17%. Conclusion We developed a system capable of predicting negative emotions based on mobile phone usage patterns. This system has potential for ecological momentary intervention (EMI) for depressive disorders by automatically recognizing negative emotions and providing people with preventive treatments before it

  6. Conservation of CFTR codon frequency through primates suggests synonymous mutations could have a functional effect.

    PubMed

    Pizzo, Lucilla; Iriarte, Andrés; Alvarez-Valin, Fernando; Marín, Mónica

    2015-05-01

    Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system, with a prevalence of about 1:3000 people. Cystic fibrosis is caused by mutations in CFTR gene, which lead to a defective function of the chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Up-to-date, more than 1900 mutations have been reported in CFTR. However for an important proportion of them, their functional effects and the relation to disease are still not understood. Many of these mutations are silent (or synonymous), namely they do not alter the encoded amino acid. These synonymous mutations have been considered as neutral to protein function. However, more recent evidence in bacterial and human proteins has put this concept under revision. With the aim of understanding possible functional effects of synonymous mutations in CFTR, we analyzed human and primates CFTR codon usage and divergence patterns. We report the presence of regions enriched in rare and frequent codons. This spatial pattern of codon preferences is conserved in primates, but this cannot be explained by sequence conservation alone. In sum, the results presented herein suggest a functional implication of these regions of the gene that may be maintained by purifying selection acting to preserve a particular codon usage pattern along the sequence. Overall these results support the idea that several synonymous mutations in CFTR may have functional importance, and could be involved in the disease. PMID:25839760

  7. Evaluation of codon biology in citrus and Poncirus trifoliata based on genomic features and frame corrected expressed sequence tags.

    PubMed

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

    2013-04-01

    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. PMID:23315666

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

    PubMed Central

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

    2013-01-01

    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. PMID:23315666

  9. Usage patterns and adverse experiences in traditional Korean medicine: results of a survey in South Korea

    PubMed Central

    2013-01-01

    Background Although traditional medicine (TM) in South Korea is included in the national health care system, it is considered complementary and alternative medicine (CAM), and not mainstream medicine. Therefore, the lack of statistical data regarding the usage and adverse experiences of traditional Korean medicine (TKM) makes difficult to understand the current status of TM. In this study, we aimed to report usage patterns and adverse experiences on TKM targeting consumers in South Korea. Methods A total of 2000 consumers participated in the survey on usage and adverse experiences in 2008. Among the 2,000 participants, 915 (45.8%) had taken herbal medicine or received traditional medicinal therapies; these individuals were further surveyed on the internet or in an interview. Results The usage rate was higher among women and among patients in their 30s. Of the total TKM usage, acupuncture accounted for 36.7%, and herbal medicine accounted for 13.4%. Regarding the frequency of use of TKM, 73.8% of patients reported using TM less than 5 times in 1 year. Of the 915 respondents, 8.2% of individuals had some type of adverse experience resulting from TKM. Adverse experiences were primarily caused by acupuncture and herbal medicines, and they primarily involved diseases of the digestive system and skin. The incidence of adverse experiences was less than 3.7% for acupuncture and 3.8% for herbal medicine. Overall, the incidence rate of adverse experiences for TKM for the entire population was 0.04 per 10,000 individuals. Conclusions The medical usage and occurrence of adverse events on TKM should be surveyed periodically, and the statistical trends should be analysed. The disparity between the survey results for traditional herbal medicines and medical practices, and those for the national pharmacovigilance system or academic reports of adverse experiences should be examined. The national pharmacovigilance system must be improved to compensate for the disparities. Policies

  10. Clustering of classical swine fever virus isolates by codon pair bias

    PubMed Central

    2011-01-01

    Background The genetic code consists of non-random usage of synonymous codons for the same amino acids, termed codon bias or codon usage. Codon juxtaposition is also non-random, referred to as codon context bias or codon pair bias. The codon and codon pair bias vary among different organisms, as well as with viruses. Reasons for these differences are not completely understood. For classical swine fever virus (CSFV), it was suggested that the synonymous codon usage does not significantly influence virulence, but the relationship between variations in codon pair usage and CSFV virulence is unknown. Virulence can be related to the fitness of a virus: Differences in codon pair usage influence genome translation efficiency, which may in turn relate to the fitness of a virus. Accordingly, the potential of the codon pair bias for clustering CSFV isolates into classes of different virulence was investigated. Results The complete genomic sequences encoding the viral polyprotein of 52 different CSFV isolates were analyzed. This included 49 sequences from the GenBank database (NCBI) and three newly sequenced genomes. The codon usage did not differ among isolates of different virulence or genotype. In contrast, a clustering of isolates based on their codon pair bias was observed, clearly discriminating highly virulent isolates and vaccine strains on one side from moderately virulent strains on the other side. However, phylogenetic trees based on the codon pair bias and on the primary nucleotide sequence resulted in a very similar genotype distribution. Conclusion Clustering of CSFV genomes based on their codon pair bias correlate with the genotype rather than with the virulence of the isolates. PMID:22126254

  11. Recommendation Systems for Geoscience Data Portals Built by Analyzing Usage Patterns

    NASA Astrophysics Data System (ADS)

    Crosby, C.; Nandigam, V.; Baru, C.

    2009-04-01

    Since its launch five years ago, the National Science Foundation-funded GEON Project (www.geongrid.org) has been providing access to a variety of geoscience data sets such as geologic maps and other geographic information system (GIS)-oriented data, paleontologic databases, gravity and magnetics data and LiDAR topography via its online portal interface. In addition to data, the GEON Portal also provides web-based tools and other resources that enable users to process and interact with data. Examples of these tools include functions to dynamically map and integrate GIS data, compute synthetic seismograms, and to produce custom digital elevation models (DEMs) with user defined parameters such as resolution. The GEON portal built on the Gridsphere-portal framework allows us to capture user interaction with the system. In addition to the site access statistics captured by tools like Google Analystics which capture hits per unit time, search key words, operating systems, browsers, and referring sites, we also record additional statistics such as which data sets are being downloaded and in what formats, processing parameters, and navigation pathways through the portal. With over four years of data now available from the GEON Portal, this record of usage is a rich resource for exploring how earth scientists discover and utilize online data sets. Furthermore, we propose that this data could ultimately be harnessed to optimize the way users interact with the data portal, design intelligent processing and data management systems, and to make recommendations on algorithm settings and other available relevant data. The paradigm of integrating popular and commonly used patterns to make recommendations to a user is well established in the world of e-commerce where users receive suggestions on books, music and other products that they may find interesting based on their website browsing and purchasing history, as well as the patterns of fellow users who have made similar

  12. 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

    Castro-Chavez, Fernando

    2011-01-01

    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. PMID:22997484

  13. Usage patterns of a personal health record by elderly and disabled users.

    PubMed

    Kim, Eung-Hun; Stolyar, Anna; Lober, William B; Herbaugh, Anne L; Shinstrom, Sally E; Zierler, Brenda K; Soh, Cheong B; Kim, Youngmin

    2007-01-01

    Personal Health Records (PHRs) are increasingly recognized as a strategy to improve patient-provider communication, availability of health information, and quality of care, by making the delivery of care more patient-centered. However, not much is known about the effects of self-managing personal health information (PeHI), patients' perception of PeHI and patient workflow around PeHI management. We studied PHR use in a low-income, elderly and/or disabled population for 18 months, and describe how the PHR was used through an analysis of database access server log data. Some patients may not keep their PHR up-to-date because they don't value, can't access, or don't understand certain categories of their health information. Understanding of usage patterns can guide the development and maintenance of more usable and pragmatic PHR systems. PMID:18693868

  14. Usage Patterns of a Personal Health Record by Elderly and Disabled Users

    PubMed Central

    Kim, Eung-Hun; Stolyar, Anna; Lober, William B.; Herbaugh, Anne L.; Shinstrom, Sally E.; Zierler, Brenda K.; Soh, Cheong B.; Kim, Yongmin

    2007-01-01

    Personal Health Records (PHRs) are increasingly recognized as a strategy to improve patient-provider communication, availability of health information, and quality of care, by making the delivery of care more patient-centered. However, not much is known about the effects of self-managing personal health information (PeHI), patients’ perception of PeHI and patient workflow around PeHI management. We studied PHR use in a low-income, elderly and/or disabled population for 18 months, and describe how the PHR was used through an analysis of database access server log data. Some patients may not keep their PHR up-to-date because they don’t value, can’t access, or don’t understand certain categories of their health information. Understanding of usage patterns can guide the development and maintenance of more usable and pragmatic PHR systems. PMID:18693868

  15. The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

    PubMed Central

    Sengupta, Supratim; Yang, Xiaoguang

    2007-01-01

    Many cases of nonstandard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The “gain” represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The “loss” represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is codon disappearance (CD), where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the unassigned codon mechanism, the loss occurs first, whereas in the ambiguous intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. CD is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense-to-sense reassignments cannot be explained by CD. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the unassigned codon and the ambiguous intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully. Electronic supplementary material The online version of this article (doi:10.1007/s00239-006-0284-7) contains supplementary material, which is available to authorized users. PMID:17541678

  16. Codon compression algorithms for saturation mutagenesis.

    PubMed

    Pines, Gur; Pines, Assaf; Garst, Andrew D; Zeitoun, Ramsey I; Lynch, Sean A; Gill, Ryan T

    2015-05-15

    Saturation mutagenesis is employed in protein engineering and genome-editing efforts to generate libraries that span amino acid design space. Traditionally, this is accomplished by using degenerate/compressed codons such as NNK (N = A/C/G/T, K = G/T), which covers all amino acids and one stop codon. These solutions suffer from two types of redundancy: (a) different codons for the same amino acid lead to bias, and (b) wild type amino acid is included within the library. These redundancies increase library size and downstream screening efforts. Here, we present a dynamic approach to compress codons for any desired list of amino acids, taking into account codon usage. This results in a unique codon collection for every amino acid to be mutated, with the desired redundancy level. Finally, we demonstrate that this approach can be used to design precise oligo libraries amendable to recombineering and CRISPR-based genome editing to obtain a diverse population with high efficiency. PMID:25303315

  17. Estimating Gene Expression and Codon-Specific Translational Efficiencies, Mutation Biases, and Selection Coefficients from Genomic Data Alone‡

    PubMed Central

    Gilchrist, Michael A.; Chen, Wei-Chen; Shah, Premal; Landerer, Cedric L.; Zaretzki, Russell

    2015-01-01

    Extracting biologically meaningful information from the continuing flood of genomic data is a major challenge in the life sciences. Codon usage bias (CUB) is a general feature of most genomes and is thought to reflect the effects of both natural selection for efficient translation and mutation bias. Here we present a mechanistically interpretable, Bayesian model (ribosome overhead costs Stochastic Evolutionary Model of Protein Production Rate [ROC SEMPPR]) to extract meaningful information from patterns of CUB within a genome. ROC SEMPPR is grounded in population genetics and allows us to separate the contributions of mutational biases and natural selection against translational inefficiency on a gene-by-gene and codon-by-codon basis. Until now, the primary disadvantage of similar approaches was the need for genome scale measurements of gene expression. Here, we demonstrate that it is possible to both extract accurate estimates of codon-specific mutation biases and translational efficiencies while simultaneously generating accurate estimates of gene expression, rather than requiring such information. We demonstrate the utility of ROC SEMPPR using the Saccharomyces cerevisiae S288c genome. When we compare our model fits with previous approaches we observe an exceptionally high agreement between estimates of both codon-specific parameters and gene expression levels (ρ>0.99 in all cases). We also observe strong agreement between our parameter estimates and those derived from alternative data sets. For example, our estimates of mutation bias and those from mutational accumulation experiments are highly correlated (ρ=0.95). Our estimates of codon-specific translational inefficiencies and tRNA copy number-based estimates of ribosome pausing time (ρ=0.64), and mRNA and ribosome profiling footprint-based estimates of gene expression (ρ=0.53−0.74) are also highly correlated, thus supporting the hypothesis that selection against translational inefficiency is an

  18. Usage patterns of personal care products: important factors for exposure assessment.

    PubMed

    Biesterbos, Jacqueline W H; Dudzina, Tatsiana; Delmaar, Christiaan J E; Bakker, Martine I; Russel, Frans G M; von Goetz, Natalie; Scheepers, Paul T J; Roeleveld, Nel

    2013-05-01

    Complete information regarding the use of personal care products (PCPs) by consumers is limited, but such information is crucial for realistic consumer exposure assessment. To fill this gap, a database was created with person-oriented information regarding usage patterns and circumstances of use for 32 different PCPs. Out of 2700 potential participants from the Netherlands, 516 men and women completed a digital questionnaire. The prevalence of use varied by gender, age, level of education and skin type. A high frequency of use was observed for some products (e.g. lip care products), while toothpaste, deodorant and day cream were generally used once or twice a day. The frequency of use for other PCPs varied over a wide range. The amounts of use varied largely between and within different product groups. Body lotion, sunscreen and after sun lotion were often applied on adjacent body parts. The majority of PCPs were applied in the morning, but some products, such as night cream and after sun, were predominantly applied in the evening or night. As expected, the participants used several PCPs simultaneously. The database yields important personalized exposure factors which can be used in aggregate consumer exposure assessment for substances that are components of PCPs. PMID:23174517

  19. Usage patterns of aromatherapy among the French general population: A descriptive study focusing on dermal exposure.

    PubMed

    Dornic, N; Ficheux, A S; Roudot, A C; Saboureau, D; Ezzedine, K

    2016-04-01

    Although likely benefits of aromatherapy are well documented, little is known about essential oils consumption and exposure to molecules present in the oils. The aim of our study was to determine usage patterns of 12 types of essential oils among a quite large panel, sorted per sex and quintile of age from birth to 70. A survey was conducted in September 2014 among 1507 French individuals, selected to build a representative panel of the general population. The key point of our study, apart from the fact that it has never been done among general population, was the focus on dermal exposure. Information about types of essential oils used, skin areas exposed, frequencies and quantities were collected. Our work revealed that some sub-populations could be significantly exposed to molecules of toxicological concern, especially in terms of skin sensitization. This work is the first step to assess human exposure to these molecules, and will help safety authorities and risk managers to protect the population. PMID:26826550

  20. Patterns of Stove Usage after Introduction of an Advanced Cookstove: The Long-Term Application of Household Sensors

    PubMed Central

    2015-01-01

    Household air pollution generated from solid fuel use for cooking is one of the leading risk factors for ill-health globally. Deployment of advanced cookstoves to reduce emissions has been a major focus of intervention efforts. However, household usage of these stoves and resulting changes in usage of traditional polluting stoves is not well characterized. In Palwal District, Haryana, India, we carried out an intervention utilizing the Philips HD4012 fan-assisted stove, one of the cleanest biomass stoves available. We placed small, unobtrusive data-logging iButton thermometers on both the traditional and Philips stoves to collect continuous data on use patterns in 200 homes over 60 weeks. Intervention stove usage declined steadily over time and stabilized after approximately 200 days; use of the traditional stove remained relatively constant. We additionally evaluated how well short-duration usage measures predicted long-term use. Measuring usage over time of both traditional and intervention stoves provides better understanding of cooking behaviors and can lead to more precise quantification of potential exposure reductions and consequent health benefits attributable to interventions. PMID:25390366

  1. Engagement in a Diabetes Self-management Website: Usage Patterns and Generalizability of Program Use

    PubMed Central

    2011-01-01

    visiting at least weekly during the first 6 weeks to 47% during weeks 7 to 16. There were no significant differences between website only and website plus support conditions on most of the engagement variables. In total, 75% of participants entered self-monitoring data at least once per week. Exercise action plan pages were visited more often than medication taking and healthy eating pages (mean of 4.3 visits vs 2.8 and 2.0 respectively, P < .001). Spearman nonparametric correlations indicated few significant associations between patient characteristics and summary website engagement variables, and key factors such as ethnicity, baseline computer use, age, health literacy, and education were not related to use. Partial correlations indicated that engagement, especially in self-monitoring, was most consistently related to improvement in healthy eating (r = .20, P = .04) and reduction of dietary fat (r = -.31, P = .001). There was also a significant correlation between self-monitoring and improvement in exercise (r = .20, P = .033) but not with medication taking. Conclusions Participants visited the website fairly often and used all of the theoretically important sections, but engagement decreased over 4 months. Usage rates and patterns were similar for a wide range of participants, which has encouraging implications for the potential reach of online interventions. Trial Registration NCT00987285; http://clinicaltrials.gov/show/NCT00987285 (Archived by WebCite at http://www.webcitation.org/5vpe4RHTV) PMID:21371992

  2. Stop codons in bacteria are not selectively equivalent

    PubMed Central

    2012-01-01

    Background The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes. Results We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG. Conclusions Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications. Reviewers This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section. PMID:22974057

  3. Patterns in Electronic Journal Usage: Challenging the Composition of Geographic Consortia.

    ERIC Educational Resources Information Center

    Davis, Philip M.

    2002-01-01

    Analyzed annual electronic journal usage data for the NorthEast Research Library (NERL) consortium. Discusses the high degree of skew in journal use; describes results of a cluster analysis that revealed three distinct groups of institutions based on journal use; and recommends that institutions consider their consortial membership and organize…

  4. Learning and Teaching 24/7: Daily Internet Usage Patterns at Nine Australian Universities

    ERIC Educational Resources Information Center

    Spennemann, Dirk H. R.

    2007-01-01

    Purpose: This paper seeks to look at the usage of the internet by students, academics and university administrators as part of their normal working day. It investigates whether access to computer facilities and the mode of study have any influence, or whether other factors need to be considered when providing services. Design/methodology/approach:…

  5. Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness

    NASA Astrophysics Data System (ADS)

    Villanueva, Eneko; Martí-Solano, Maria; Fillat, Cristina

    2016-06-01

    Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development.

  6. Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness.

    PubMed

    Villanueva, Eneko; Martí-Solano, Maria; Fillat, Cristina

    2016-01-01

    Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development. PMID:27278133

  7. Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness

    PubMed Central

    Villanueva, Eneko; Martí-Solano, Maria; Fillat, Cristina

    2016-01-01

    Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development. PMID:27278133

  8. Distinct pattern of p53 mutations in bladder cancer: relationship to tobacco usage.

    PubMed

    Spruck, C H; Rideout, W M; Olumi, A F; Ohneseit, P F; Yang, A S; Tsai, Y C; Nichols, P W; Horn, T; Hermann, G G; Steven, K

    1993-03-01

    A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder tumors from smokers and 13 of 40 (33%) tumors from lifetime nonsmokers. Overall, 13 of the 50 (26%) total point mutations discovered in this and previous work were G:C-->C:G transversions, a relatively rare mutational type in human tumors. In six tumors, identical AGA (Arg)-->ACA (Thr) point mutations at codon 280 were observed, suggesting a mutational hotspot in these tumors. Comparison of the mutational spectra from smokers and nonsmokers revealed no obvious differences in the types or positions of inactivating mutations; however, 5 of 15 tumors containing point mutations from cigarette smokers had double mutations, four of which were tandem mutations on the same allele. No double mutations were found in tumors from nonsmoking patients. None of the mutations in smokers were G:C-->T:A transversions, which would be anticipated for exposure to the suspected cigarette smoke carcinogen 4-aminobiphenyl. The results suggest that, although cigarette smoke exposure may not significantly alter the kinds of mutations sustained in the p53 gene, it may act to increase the extent of DNA damage per mutagenic event. PMID:8439962

  9. Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo

    PubMed Central

    Pechmann, Sebastian; Chartron, Justin W; Frydman, Judith

    2015-01-01

    The genetic code allows most amino acids a choice of optimal and nonoptimal codons. We report that synonymous codon choice is tuned to promote interaction of nascent polypeptides with the signal recognition particle (SRP), which assists in protein translocation across membranes. Cotranslational recognition by the SRP in vivo is enhanced when mRNAs contain nonoptimal codon clusters 35–40 codons downstream of the SRP-binding site, the distance that spans the ribosomal polypeptide exit tunnel. A local translation slowdown upon ribosomal exit of SRP-binding elements in mRNAs containing these nonoptimal codon clusters is supported experimentally by ribosome profiling analyses in yeast. Modulation of local elongation rates through codon choice appears to kinetically enhance recognition by ribosome-associated factors. We propose that cotranslational regulation of nascent-chain fate may be a general constraint shaping codon usage in the genome. PMID:25420103

  10. Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo.

    PubMed

    Pechmann, Sebastian; Chartron, Justin W; Frydman, Judith

    2014-12-01

    The genetic code allows most amino acids a choice of optimal and nonoptimal codons. We report that synonymous codon choice is tuned to promote interaction of nascent polypeptides with the signal recognition particle (SRP), which assists in protein translocation across membranes. Cotranslational recognition by the SRP in vivo is enhanced when mRNAs contain nonoptimal codon clusters 35-40 codons downstream of the SRP-binding site, the distance that spans the ribosomal polypeptide exit tunnel. A local translation slowdown upon ribosomal exit of SRP-binding elements in mRNAs containing these nonoptimal codon clusters is supported experimentally by ribosome profiling analyses in yeast. Modulation of local elongation rates through codon choice appears to kinetically enhance recognition by ribosome-associated factors. We propose that cotranslational regulation of nascent-chain fate may be a general constraint shaping codon usage in the genome. PMID:25420103

  11. Translationally optimal codons associate with aggregation-prone sites in proteins.

    PubMed

    Lee, Yaelim; Zhou, Tong; Tartaglia, Gian Gaetano; Vendruscolo, Michele; Wilke, Claus O

    2010-12-01

    We analyze the relationship between codon usage bias and residue aggregation propensity in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse, as well as the archaeon Halobacterium species NRC-1. Using the Mantel-Haenszel procedure, we find that translationally optimal codons associate with aggregation-prone residues. Our results are qualitatively and quantitatively similar to those of an earlier study where we found an association between translationally optimal codons and buried residues. We also combine the aggregation-propensity data with solvent-accessibility data. Although the resulting data set is small, and hence statistical power low, results indicate that the association between optimal codons and aggregation-prone residues exists both at buried and at exposed sites. By comparing codon usage at different combinations of sites (exposed, aggregation-prone sites versus buried, non-aggregation-prone sites; buried, aggregation-prone sites versus exposed, non-aggregation-prone sites), we find that aggregation propensity and solvent accessibility seem to have independent effects of (on average) comparable magnitude on codon usage. Finally, in fly, we assess whether optimal codons associate with sites at which amino acid substitutions lead to an increase in aggregation propensity, and find only a very weak effect. These results suggest that optimal codons may be required to reduce the frequency of translation errors at aggregation-prone sites that coincide with certain functional sites, such as protein-protein interfaces. Alternatively, optimal codons may be required for rapid translation of aggregation-prone regions. PMID:21046618

  12. Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously identified the mycobacterial high G+C codon usage bias as a limiting factor in heterologous expression of MAP proteins from Lb.salivarius, and demonstrated that codon optimisation of a synthetic coding gene greatly enhances MAP protein production. Here, we effectively demonstrate ...

  13. Usage patterns of ‘over-the-counter’ vs. prescription-strength nonsteroidal anti-inflammatory drugs in France

    PubMed Central

    Duong, Mai; Salvo, Francesco; Pariente, Antoine; Abouelfath, Abdelilah; Lassalle, Regis; Droz, Cecile; Blin, Patrick; Moore, Nicholas

    2014-01-01

    Aims Most risks of nonsteroidal anti-inflammatory drugs (NSAIDs) are pharmacological, dose and duration dependent. Usage patterns of prescription-only (POM) or ‘over-the-counter (OTC)’ NSAIDs may influence risks, but are not commonly described. Methods The Echantillon Généraliste de Bénéficiaires database, the permanent 1/97 representative sample from the French national healthcare insurance systems, was queried over 2009–2010 to identify usage patterns, concomitant chronic diseases and cardiovascular medication in OTC and POM NSAID users. Results Over 2 years, 229 477 of 526 108 patients had at least one NSAID dispensation; 44 484 patients (19%) were dispensed only OTC NSAIDs (93% ibuprofen) and 121 208 (53%) only POM NSAIDs. The OTC users were younger (39.9 vs. 47.4 years old) and more often female (57 vs. 53%); 69% of OTC users and 49% of POM users had only one dispensation. A mean of 14.6 defined daily doses (DDD) were dispensed over 2 years for OTC vs. 53 for POM; 93% OTC vs. 60% POM patients bought ≤ 30 DDD over 2 years, and 1.5 vs. 12% bought ≥ 90 DDD. Chronic comorbidities were found in 19% of OTC users vs. 28% of POM users; 24 vs. 37% had at least one dispensation of a cardiovascular drug over the 2 years. Conclusions Most of the use of NSAIDs appears to be short term, especially for OTC-type NSAIDs, such as ibuprofen. The validity of risk estimates for NSAIDs extrapolated from clinical trials or from observational studies not including OTC-type usage may need to be revised. PMID:24102791

  14. Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States

    PubMed Central

    Villar, Diego; White, Robert J.; Marioni, John C.; Kutter, Claudia

    2016-01-01

    Whether codon usage fine-tunes mRNA translation in mammals remains controversial, with recent papers suggesting that production of proteins in specific Gene Ontological (GO) pathways can be regulated by actively modifying the codon and anticodon pools in different cellular conditions. In this work, we compared the sequence content of genes in specific GO categories with the exonic genome background. Although a substantial fraction of variability in codon usage could be explained by random sampling, almost half of GO sets showed more variability in codon usage than expected by chance. Nevertheless, by quantifying translational efficiency in healthy and cancerous tissues in human and mouse, we demonstrated that a given tRNA pool can equally well translate many different sets of mRNAs, irrespective of their cell-type specificity. This disconnect between variations in codon usage and the stability of translational efficiency is best explained by differences in GC content between gene sets. GC variation across the mammalian genome is most likely a result of the interplay between genome repair and gene duplication mechanisms, rather than selective pressures caused by codon-driven translational rates. Consequently, codon usage differences in mammalian transcriptomes are most easily explained by well-understood mutational biases acting on the underlying genome. PMID:27166679

  15. Initial Report on In Situ Measurements of Major Anthropogenic Halocarbons for Understanding Trends and Usage Patterns in Northeast Asia

    NASA Astrophysics Data System (ADS)

    Kim, J.; Li, S.; Muhle, J.; Lee, G.; Salameh, P. K.; Harth, C. M.; Weiss, R. F.; Kim, K.

    2009-12-01

    In this study we provide analysis of in situ measurements of most major halocarbons at Gosan station (126°E, 33°N, Jeju Island, Korea) for the period of November ’07 ~ February ’09. Species presented in this study include major CFCs (CFC-11, CFC-12), HCFCs (HCFC-22, HCFC-141b, HCFC-142b), HFCs (HFC-134a, HFC-125, HFC-152a, HFC-23, HFC-143a, HFC-32), H-1211, PFCs(CF4, PFC-116, PFC-218) solvents (CH3Cl, CH2Cl2, CHCl3, CCl4) and SF6. 2-hourly ambient measurements were conducted using a Gas Chromatography/Mass Spectrometry system developed and operated under the Advanced Global Atmospheric Gases Experiment (AGAGE) project. General trends in the baseline are reflective of global usage patterns, and are similar to values reported for other baseline stations in the Northern Hemisphere, however summer concentrations show a decrease in concentrations comparable to Southern Hemispheric levels mostly due to southern air masses reaching Gosan. Pollution occurrences (mostly from China and Korea) show different patterns depending on various emission source types, many of which are specific to each country. For example, strong influence of HFC-23 is observed from China, major sources for which are from HCFC-22 production. On the other hand, stronger pollution magnitudes for SF6 occur from Korean air masses, suggesting perhaps that larger emissions occur in the high-tech industries in Korea as opposed to China. Future measurements will provide important insight to changes in usage patterns, such as adherence to the Montreal and Kyoto protocols, and industrial adoption patterns of specific compounds.

  16. Hand gesture recognition by analysis of codons

    NASA Astrophysics Data System (ADS)

    Ramachandra, Poornima; Shrikhande, Neelima

    2007-09-01

    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.

  17. A Study on Pubmed Search Tag Usage Pattern: Association Rule Mining of a Full-day Pubmed Query Log

    PubMed Central

    2013-01-01

    Background The practice of evidence-based medicine requires efficient biomedical literature search such as PubMed/MEDLINE. Retrieval performance relies highly on the efficient use of search field tags. The purpose of this study was to analyze PubMed log data in order to understand the usage pattern of search tags by the end user in PubMed/MEDLINE search. Methods A PubMed query log file was obtained from the National Library of Medicine containing anonymous user identification, timestamp, and query text. Inconsistent records were removed from the dataset and the search tags were extracted from the query texts. A total of 2,917,159 queries were selected for this study issued by a total of 613,061 users. The analysis of frequent co-occurrences and usage patterns of the search tags was conducted using an association mining algorithm. Results The percentage of search tag usage was low (11.38% of the total queries) and only 2.95% of queries contained two or more tags. Three out of four users used no search tag and about two-third of them issued less than four queries. Among the queries containing at least one tagged search term, the average number of search tags was almost half of the number of total search terms. Navigational search tags are more frequently used than informational search tags. While no strong association was observed between informational and navigational tags, six (out of 19) informational tags and six (out of 29) navigational tags showed strong associations in PubMed searches. Conclusions The low percentage of search tag usage implies that PubMed/MEDLINE users do not utilize the features of PubMed/MEDLINE widely or they are not aware of such features or solely depend on the high recall focused query translation by the PubMed’s Automatic Term Mapping. The users need further education and interactive search application for effective use of the search tags in order to fulfill their biomedical information needs from PubMed/MEDLINE. PMID:23302604

  18. Control of Turing patterns and their usage as sensors, memory arrays, and logic gates

    NASA Astrophysics Data System (ADS)

    Muzika, František; Schreiber, Igor

    2013-10-01

    We study a model system of three diffusively coupled reaction cells arranged in a linear array that display Turing patterns with special focus on the case of equal coupling strength for all components. As a suitable model reaction we consider a two-variable core model of glycolysis. Using numerical continuation and bifurcation techniques we analyze the dependence of the system's steady states on varying rate coefficient of the recycling step while the coupling coefficients of the inhibitor and activator are fixed and set at the ratios 100:1, 1:1, and 4:5. We show that stable Turing patterns occur at all three ratios but, as expected, spontaneous transition from the spatially uniform steady state to the spatially nonuniform Turing patterns occurs only in the first case. The other two cases possess multiple Turing patterns, which are stabilized by secondary bifurcations and coexist with stable uniform periodic oscillations. For the 1:1 ratio we examine modular spatiotemporal perturbations, which allow for controllable switching between the uniform oscillations and various Turing patterns. Such modular perturbations are then used to construct chemical computing devices utilizing the multiple Turing patterns. By classifying various responses we propose: (a) a single-input resettable sensor capable of reading certain value of concentration, (b) two-input and three-input memory arrays capable of storing logic information, (c) three-input, three-output logic gates performing combinations of logical functions OR, XOR, AND, and NAND.

  19. Is health literacy related to health behaviors and cell phone usage patterns among the text4baby target population?

    PubMed Central

    2014-01-01

    Background Text4baby provides educational text messages to pregnant and postpartum women and targets underserved women. The primary purpose of this study is to examine the health behaviors and cell phone usage patterns of a text4baby target population and the associations with health literacy. Methods Pregnant and postpartum women were recruited from two Women, Infant and Children clinics in Atlanta. Women were asked about their demographics, selected pregnancy or postpartum health behaviors, and cell phone usage patterns. Health literacy skills were measured with the English version of the Newest Vital Sign. Multivariable logistic regression was used to examine health behaviors and cell usage patterns by health literacy classification, controlling for commonly accepted confounders. Results Four hundred sixty-eight women were recruited, and 445 completed the Newest Vital Sign. Of these, 22% had inadequate health literacy, 50% had intermediate health literacy, and 28% had adequate health literacy skills. Compared to adequate health literacy, limited literacy was independently associated with not taking a daily vitamin during pregnancy (OR 3.6, 95% CI: 1.6, 8.5) and never breastfeeding their infant (OR 1.4, 95% CI: 1.1, 1.8). The majority (69.4%) of respondents received nine or more text messages a day prior to enrollment, one in four participants (24.6%) had changed their number within the last six months, and 7.0% of study participants shared a cell phone. Controlling for potentially confounding factors, those with limited health literacy were more likely to share a cell phone than those with adequate health literacy (OR 2.57, 95% CI: 1.79, 3.69). Conclusions Text4baby messages should be appropriate for low health literacy levels, especially as this population may have higher prevalence of targeted unhealthy behaviors. Text4baby and other mhealth programs targetting low health literacy populations should also be aware of the different ways that these populations

  20. Identifying the usage patterns of methyl tert-butyl ether (MTBE) and other oxygenates in gasoline using gasoline surveys

    USGS Publications Warehouse

    Moran, M.J.; Clawges, R.M.; Zogorski, J.S.

    2000-01-01

    Data on the volumes of oxygenates and other compounds in gasoline are available from several sources collectively referred as gasoline surveys. The gasoline surveys provide the most definitive knowledge of which oxygenate, if any, and what volumes of that oxygenate are being used in various areas of the country. This information is important in water-quality assessments for relating the detection of MTBE in water to patterns of usage of MTBE in gasoline. General information on three surveys that have been conducted by the National Institute for Petroleum and Energy Research, the Motor Vehicle Manufacturers Association, and the EPA was presented. The samples were tested for physical properties and constituents including octane number, specific gravity, and volumes of olefins, aromatics, benzene, alcohols, and various ether oxygenates. The data in each survey had its own utility based on the type of assessment that is undertaken. Quality Assessment (NAWQA) Program. Using NAWQA data, the percent occurrence of MTBE in ground water in metropolitan areas that use substantial amounts of MTBE (> 5% by vol) was ??? 21%, compared to ??? 2% in areas that do not use substantial amounts of MTBE (< 5% by vol). When several other factors are considered in a logistic regression model including MTBE usage in RFG or OXY gasoline areas (??? 3% by vol) as a factor, a 4-6 fold increase in the detection frequency of MTBE in ground water was found when compared to areas that do not use MTBE or use it only for octane enhancement (< 3% by vol).

  1. Influences of population density on polyandry and patterns of sperm usage in the marine gastropod Rapana venosa

    PubMed Central

    Xue, Dong-Xiu; Zhang, Tao; Liu, Jin-Xian

    2016-01-01

    Polyandry is a common mating strategy in animals, with potential for sexual selection to continue post-copulation through sperm competition and/or cryptic female choice. Few studies have investigated the influences of population density on polyandry and sperm usage, and paternity distribution in successive broods of marine invertebrates. The marine gastropod Rapana venosa is ideal for investigating how population density influences the frequency of polyandry and elucidating patterns of sperm usage. Two different population density (12 ind/m3 and 36 ind/m3) treatments with two replications were set to observe reproductive behaviors. Five microsatellite markers were used to identify the frequency of multiple paternity and determine paternal contributions to progeny arrays in 120 egg masses. All of the mean mating frequency, mean number of sires and mean egg-laying frequency were higher at high population density treatment relative to low population density treatment, indicating population density is an important factor affecting polyandry. The last sperm donors achieved high proportions of paternity in 74.77% of egg masses, which supported the “last male sperm precedence” hypothesis. In addition, high variance in reproductive success among R. venosa males were detected, which might have an important influence on effective population size. PMID:26996441

  2. Influences of population density on polyandry and patterns of sperm usage in the marine gastropod Rapana venosa.

    PubMed

    Xue, Dong-Xiu; Zhang, Tao; Liu, Jin-Xian

    2016-01-01

    Polyandry is a common mating strategy in animals, with potential for sexual selection to continue post-copulation through sperm competition and/or cryptic female choice. Few studies have investigated the influences of population density on polyandry and sperm usage, and paternity distribution in successive broods of marine invertebrates. The marine gastropod Rapana venosa is ideal for investigating how population density influences the frequency of polyandry and elucidating patterns of sperm usage. Two different population density (12 ind/m(3) and 36 ind/m(3)) treatments with two replications were set to observe reproductive behaviors. Five microsatellite markers were used to identify the frequency of multiple paternity and determine paternal contributions to progeny arrays in 120 egg masses. All of the mean mating frequency, mean number of sires and mean egg-laying frequency were higher at high population density treatment relative to low population density treatment, indicating population density is an important factor affecting polyandry. The last sperm donors achieved high proportions of paternity in 74.77% of egg masses, which supported the "last male sperm precedence" hypothesis. In addition, high variance in reproductive success among R. venosa males were detected, which might have an important influence on effective population size. PMID:26996441

  3. Stop Codon Reassignment in the Wild

    SciTech Connect

    Ivanova, Natalia; Schwientek, Patrick; Tripp, H. James; Rinke, Christian; Pati, Amrita; Huntemann, Marcel; Visel, Axel; Woyke, Tanja; Kyrpides, Nikos; Rubin, Edward

    2014-03-21

    Since the discovery of the genetic code and protein translation mechanisms (1), a limited number of variations of the standard assignment between unique base triplets (codons) and their encoded amino acids and translational stop signals have been found in bacteria and phages (2-3). Given the apparent ubiquity of the canonical genetic code, the design of genomically recoded organisms with non-canonical codes has been suggested as a means to prevent horizontal gene transfer between laboratory and environmental organisms (4). It is also predicted that genomically recoded organisms are immune to infection by viruses, under the assumption that phages and their hosts must share a common genetic code (5). This paradigm is supported by the observation of increased resistance of genomically recoded bacteria to phages with a canonical code (4). Despite these assumptions and accompanying lines of evidence, it remains unclear whether differential and non-canonical codon usage represents an absolute barrier to phage infection and genetic exchange between organisms. Our knowledge of the diversity of genetic codes and their use by viruses and their hosts is primarily derived from the analysis of cultivated organisms. Advances in single-cell sequencing and metagenome assembly technologies have enabled the reconstruction of genomes of uncultivated bacterial and archaeal lineages (6). These initial findings suggest that large scale systematic studies of uncultivated microorganisms and viruses may reveal the extent and modes of divergence from the canonical genetic code operating in nature. To explore alternative genetic codes, we carried out a systematic analysis of stop codon reassignments from the canonical TAG amber, TGA opal, and TAA ochre codons in assembled metagenomes from environmental and host-associated samples, single-cell genomes of uncultivated bacteria and archaea, and a collection of phage sequences

  4. Stochastic Modeling of Usage Patterns in a Web-Based Information System.

    ERIC Educational Resources Information Center

    Chen, Hui-Min; Cooper, Michael D.

    2002-01-01

    Uses continuous-time stochastic models, mainly based on semi-Markov chains, to derive user state transition patterns, both in rates and in probabilities, in a Web-based information system. Describes search sessions from transaction logs of the University of California's MELVYL library catalog system and discusses sequential dependency. (Author/LRW)

  5. Screening for male osteoporosis at an academic medical center: retrospective analysis of DXA usage patterns over 5 years.

    PubMed

    Ivory, Dedri Markita; Siva, Chokkalingam; Velázquez, Celso; Abdinoor, Abdillahi Abdi

    2012-01-01

    Recent findings suggest that men have higher mortality rates than women after a hip fracture. Although the risk of osteoporotic fractures in men is increasing, male osteoporosis still remains underdiagnosed and undertreated. In general, male osteoporosis is given low priority by policy makers in public health initiatives. The purpose of this study is to examine the patterns of use and gender distribution of DXA (dual-energy X-ray absorptiometry) scan usage at a university medical center in the United States. The total number of DXA scans increased during the study period while the percentage of men studied actually declined. The results of this study may lead to heightened awareness among providers who are caring for male patients at risk for osteoporosis. PMID:21956247

  6. Analyzing PACS Usage Patterns by Means of Process Mining: Steps Toward a More Detailed Workflow Analysis in Radiology.

    PubMed

    Forsberg, Daniel; Rosipko, Beverly; Sunshine, Jeffrey L

    2016-02-01

    In this paper, statistical analysis and techniques from process mining are employed to analyze interaction patterns originating from radiologists reading medical images in a picture archiving and communication system (PACS). Event logs from 1 week of data, corresponding to 567 cases of single-view chest radiographs read by 14 radiologists, were analyzed. Statistical analysis showed that the numbers of commands and command types used by the radiologists per case only have a slightly positive correlation with the time to read a case (0.31 and 0.55, respectively). Further, one way ANOVA showed that the factors time of day, radiologist and specialty were significant for the number of commands per case, whereas radiologist was also significant for the number of command types, but with no significance of any of the factors on time to read. Applying process mining to the event logs of all users showed that a seemingly "simple" examination (single-view chest radiographs) can be associated with a highly complex interaction process. However, repeating the process discovery on each individual radiologist revealed that the initially discovered complex interaction process consists of one group of radiologists with individually well-structured interaction processes and a second smaller group of users with progressively more complex usage patterns. Future research will focus on metrics to describe derived interaction processes in order to investigate if one set of interaction patterns can be considered as more efficient than another set when reading radiological images in a PACS. PMID:26353749

  7. Radiocarbon dating Arctic deep marine sediment to refine the usage of Mn pattern as a stratigraphic tool

    NASA Astrophysics Data System (ADS)

    Chiu, Pin-Yao Bernie; Löwemark, Ludvig

    2016-04-01

    , the loss core tops and glacial hiatuses limits the usage and accuracy of the correlation of Mn stratigraphies. Therefore, additional radiocarbon dating can refine our understanding of the Mn patterns in Arctic marine sediment and help to make it a better proxy for both paleoenvironmental reconstructions and for the age models. Further study on the cause of hiatus often encountered in the LGM interval is necessary to ensure the usefulness of Mn stratigraphy.

  8. Ringxiety and the Mobile Phone Usage Pattern among the Students of a Medical College in South India

    PubMed Central

    Subba, Sonu H.; Mandelia, Chetan; Pathak, Vaibhav; Reddy, Divya; Goel, Akanksha; Tayal, Ayushi; Nair, Swati; Nagaraj, Kondagunta

    2013-01-01

    Aims: Technologies like mobile phones may not always work positively but they may have unforeseen adverse effects. This study was conducted to find the proportion of students who experienced ringxiety (phantom ringing) and other perceived effects, as well as the pattern of the mobile phone usage among college students. Method: A cross-sectional study was carried out at Kasturba Medical College, Mangalore, south India, among 336 medical students by using a pre-tested, semi-structured questionnaire. Results: Among the total number of students, 335 students possessed mobile phones. Mostly, the persons whom they talked to on their phones were parents for 220 (51%) of the students. 48% (150) talked for less than half hour in a day and 41% (137) were high volume message users. “Ringxiety” was experienced by 34.5% (116) of the students and they were more likely to use their phones at restricted places like classrooms (99%) and libraries (60.3%). A significantly larger proportion of ringxiety sufferers also complained of hampered studies. Conclusion: The pattern of mobile phone use among the medical students appeared to be problematic, as a fairly large proportion suffered from ringxiety, they reported getting very upset and they used their phones at restricted times and places. This problem needs to be recognized, all stakeholders must be made aware of the symptoms and measures must be taken to reduce it. PMID:23542709

  9. English language usage pattern in China mainland doctors: AME survey-001 initial analysis results

    PubMed Central

    Zhang, Zhongheng

    2015-01-01

    Purpose English is the most widely used language in medical community worldwide. Till now there is no study yet on how English language is being used among mainland Chinese doctors. The present survey aimed to address this question. Methods An online cross-sectional survey was carried out during the period of 23 Oct 2014 to 13 November 2014, totaling 22 days. This survey was conducted on the platform provided by DXY (www.dxy.cn), which is the largest medical and paramedical related website in China with registered medical doctor users of slightly more than one million. E-mails were sent to all DXY registered users to invite them to participate the survey which lasts approximately five-minute. The questionnaire included three major aspects: (I) the demographic characteristics of participants; (II) English reading pattern; and (III) paper publishing experience in international journals. To accommodate the complexity of relationships among variables, structural equation modeling (SEM) was employed to build the model. Results In total 1,663 DXY users completed the survey, which counted for ≈1% of the total registered medical doctor users. There were more participants from relatively economically developed eastern coast areas. The age of participants was 33.6±7.4 years. There were 910 respondents from teaching hospitals (54.72%), followed by tertiary care hospitals (class-III hospital, 22.37%). Mainland Chinese doctors were more likely to consult medical materials in Chinese (63.5%) when they encounter clinical difficulties. Participants who were able to list English journals of their own specialty up to four were 44.02% for 0, 13.77% for one journal, 13.89% for two journals, 9.26% for three journals, and 19.06% for four journals. Most participants (82.86%) have read at least one English paper or one professional book in English, while 17.14% responded they never read a single English paper or professorial book in English. About 30.42% participants published at least

  10. Optimal codons in Tremella fuciformis end in C/G, a strong difference with known Tremella species.

    PubMed

    Deng, Youjin; Huang, Xiaoxing; Ruan, Banzhan; Xie, Baogui; van Peer, Arend Frans; Jiang, Yuji

    2015-11-01

    Tremella fuciformis is a popular edible fungus with fruiting bodies that can be produced in large quantities at low costs, while it is easy to transform and cultivate as yeast. This makes it an attractive potential bioreactor. Enhanced heterologous gene expression through codon optimization would be useful, but until now codon usage preferences in T. fuciformis remain unknown. To precisely determine the preferred codon usage of T. fuciformis we sequenced the genome of strain Tr26 resulting in a 24.2 Mb draft genome with 10,040 predicted genes. 3288 of the derived predicted proteins matched the UniProtKB/Swiss-Prot databases with 40% or more similarity. Corresponding gene models of this subset were subsequently optimized through repetitive comparison of alternative start codons and selection of best length matching gene models. For experimental confirmation of gene models, 96 random clones from an existing T. fuciformis cDNA library were sequenced, generating 80 complete CDSs. Calculated optimal codons for the 3288 predicted and the 80 cloned CDSs were highly similar, indicating sufficient accuracy of predicted gene models for codon usage analysis. T. fuciformis showed a strong preference for C and then G at the third base pair position of used codons, while average GC content of predicted genes was slightly higher than the total genome sequence average. Most optimal codons ended in C or G except for one, and an increased frequency of C ending codons was observed in genes with higher expression levels. Surprisingly, the preferred codon usage in T. fuciformis strongly differed from T. mesenterica and C. neoformans. Instead, optimal codon usage was similar to more distant related species such as Ustilago maydis and Neurospora crassa. Despite much higher overall sequence homology between T. fuciformis and T. mesenterica, only 7 out of 21 optimal codons were equal, whereas T. fuciformis shared up to 20 out of 21 optimal codons with other species. Clearly, codon usage in

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

    NASA Astrophysics Data System (ADS)

    Mitarai, Namiko; Pedersen, Steen

    2013-10-01

    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.

  12. REDOX regulation of IL-13 signaling in intestinal epithelial cells: usage of alternate pathways mediates distinct gene expression patterns

    PubMed Central

    Mandal, Debasmita; Fu, Pingfu; Levine, Alan D.

    2010-01-01

    In the classic view interleukin-13 (IL-13) binds to a heterodimer protein complex of the IL-13Rα1 and IL-4Rα chains and signals through a janus kinase 1 (JAK1)-signal transducer and activator of transcription 6 (STAT6) mechanism. We recently reported that IL-13 also signals through the IL-13Rα2 chain initiating all three mitogen activated protein kinase (MAPK) pathways, and the relative expression of IL-13Rα1 and IL-13Rα2 modulates one another’s transduction pathway. Therefore we investigated whether generation of reactive oxygen species (ROS) as second messengers may serve as a common nexus between these two pathways emanating from the individual IL-13 receptor chains in intestinal epithelial cells (IEC). IL-13 stimulates intracellular ROS synthesis within 5 min via IL-13Rα1-JAK1-STAT6- and IL-13Rα2-MEK1/2-ERK1/2-dependent activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 (NOX-1). IL-13-induced ROS generation in turn positively regulates phosphorylation of ERK1/2 and STAT6, yielding a feed forward amplification loop. IL-13 also stimulates the stable, long-term gene expression of two other NADPH oxidases, NOX-4 and DUOX-2, which along with constitutive NOX-1, might facilitate elevated, continuous production of ROS in IL-13-activated IEC. The contribution of each signal transduction pathway initiated by IL-13 engagement to such biological functions as wound healing, inflammation, and apoptosis was mapped for representative, responsive genes. Distinct usage patterns were observed, demonstrating that not only is IL-13 signal transduction through STAT6, MAPK, and ROS regulated in both an antagonistic and cyclic fashion, but each pathway also plays a specific role in modulating the wound healing and anti-apoptotic capabilities of the intestinal epithelium. PMID:20570727

  13. Vertebrate codon bias indicates a highly GC-rich ancestral genome.

    PubMed

    Nabiyouni, Maryam; Prakash, Ashwin; Fedorov, Alexei

    2013-04-25

    Two factors are thought to have contributed to the origin of codon usage bias in eukaryotes: 1) genome-wide mutational forces that shape overall GC-content and create context-dependent nucleotide bias, and 2) positive selection for codons that maximize efficient and accurate translation. Particularly in vertebrates, these two explanations contradict each other and cloud the origin of codon bias in the taxon. On the one hand, mutational forces fail to explain GC-richness (~60%) of third codon positions, given the GC-poor overall genomic composition among vertebrates (~40%). On the other hand, positive selection cannot easily explain strict regularities in codon preferences. Large-scale bioinformatic assessment, of nucleotide composition of coding and non-coding sequences in vertebrates and other taxa, suggests a simple possible resolution for this contradiction. Specifically, we propose that the last common vertebrate ancestor had a GC-rich genome (~65% GC). The data suggest that whole-genome mutational bias is the major driving force for generating codon bias. As the bias becomes prominent, it begins to affect translation and can result in positive selection for optimal codons. The positive selection can, in turn, significantly modulate codon preferences. PMID:23376453

  14. Computational codon optimization of synthetic gene for protein expression

    PubMed Central

    2012-01-01

    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. PMID:23083100

  15. Usage Automata

    NASA Astrophysics Data System (ADS)

    Bartoletti, Massimo

    Usage automata are an extension of finite stata automata, with some additional features (e.g. parameters and guards) that improve their expressivity. Usage automata are expressive enough to model security requirements of real-world applications; at the same time, they are simple enough to be statically amenable, e.g. they can be model-checked against abstractions of program usages. We study here some foundational aspects of usage automata. In particular, we discuss about their expressive power, and about their effective use in run-time mechanisms for enforcing usage policies.

  16. The Effect of an Alternate Start Codon on Heterologous Expression of a PhoA Fusion Protein in Mycoplasma gallisepticum.

    PubMed

    Panicker, Indu S; Browning, Glenn F; Markham, Philip F

    2015-01-01

    While the genomes of many Mycoplasma species have been sequenced, there are no collated data on translational start codon usage, and the effects of alternate start codons on gene expression have not been studied. Analysis of the annotated genomes found that ATG was the most prevalent translational start codon among Mycoplasma spp. However in Mycoplasma gallisepticum a GTG start codon is commonly used in the vlhA multigene family, which encodes a highly abundant, phase variable lipoprotein adhesin. Therefore, the effect of this alternate start codon on expression of a reporter PhoA lipoprotein was examined in M. gallisepticum. Mutation of the start codon from ATG to GTG resulted in a 2.5 fold reduction in the level of transcription of the phoA reporter, but the level of PhoA activity in the transformants containing phoA with a GTG start codon was only 63% of that of the transformants with a phoA with an ATG start codon, suggesting that GTG was a more efficient translational initiation codon. The effect of swapping the translational start codon in phoA reporter gene expression was less in M. gallisepticum than has been seen previously in Escherichia coli or Bacillus subtilis, suggesting the process of translational initiation in mycoplasmas may have some significant differences from those used in other bacteria. This is the first study of translational start codon usage in mycoplasmas and the impact of the use of an alternate start codon on expression in these bacteria. PMID:26010086

  17. The Effect of an Alternate Start Codon on Heterologous Expression of a PhoA Fusion Protein in Mycoplasma gallisepticum

    PubMed Central

    Panicker, Indu S.; Browning, Glenn F.; Markham, Philip F.

    2015-01-01

    While the genomes of many Mycoplasma species have been sequenced, there are no collated data on translational start codon usage, and the effects of alternate start codons on gene expression have not been studied. Analysis of the annotated genomes found that ATG was the most prevalent translational start codon among Mycoplasma spp. However in Mycoplasma gallisepticum a GTG start codon is commonly used in the vlhA multigene family, which encodes a highly abundant, phase variable lipoprotein adhesin. Therefore, the effect of this alternate start codon on expression of a reporter PhoA lipoprotein was examined in M. gallisepticum. Mutation of the start codon from ATG to GTG resulted in a 2.5 fold reduction in the level of transcription of the phoA reporter, but the level of PhoA activity in the transformants containing phoA with a GTG start codon was only 63% of that of the transformants with a phoA with an ATG start codon, suggesting that GTG was a more efficient translational initiation codon. The effect of swapping the translational start codon in phoA reporter gene expression was less in M. gallisepticum than has been seen previously in Escherichia coli or Bacillus subtilis, suggesting the process of translational initiation in mycoplasmas may have some significant differences from those used in other bacteria. This is the first study of translational start codon usage in mycoplasmas and the impact of the use of an alternate start codon on expression in these bacteria. PMID:26010086

  18. Decoding Mechanisms by which Silent Codon Changes Influence Protein Biogenesis and Function

    PubMed Central

    Bali, Vedrana; Bebok, Zsuzsanna

    2015-01-01

    Scope Synonymous codon usage has been a focus of investigation since the discovery of the genetic code and its redundancy. The occurrences of synonymous codons vary between species and within genes of the same genome, known as codon usage bias. Today, bioinformatics and experimental data allow us to compose a global view of the mechanisms by which the redundancy of the genetic code contributes to the complexity of biological systems from affecting survival in prokaryotes, to fine tuning the structure and function of proteins in higher eukaryotes. Studies analyzing the consequences of synonymous codon changes in different organisms have revealed that they impact nucleic acid stability, protein levels, structure and function without altering amino acid sequence. As such, synonymous mutations inevitably contribute to the pathogenesis of complex human diseases. Yet, fundamental questions remain unresolved regarding the impact of silent mutations in human disorders. In the present review we describe developments in this area concentrating on mechanisms by which synonymous mutations may affect protein function and human health. Purpose This synopsis illustrates the significance of synonymous mutations in disease pathogenesis. We review the different steps of gene expression affected by silent mutations, and assess the benefits and possible harmful effects of codon optimization applied in the development of therapeutic biologics. Physiological and medical relevance Understanding mechanisms by which synonymous mutations contribute to complex diseases such as cancer, neurodegeneration and genetic disorders, including the limitations of codon-optimized biologics, provides insight concerning interpretation of silent variants and future molecular therapies. PMID:25817479

  19. CodHonEditor: Spreadsheets for Codon Optimization and Editing of Protein Coding Sequences.

    PubMed

    Takai, Kazuyuki

    2016-05-01

    Gene synthesis is getting more important with the growing availability of low-cost commercial services. The coding sequences are often "optimized" as for the relative synonymous codon usage (RSCU) before synthesis, which is generally included in the commercial services. However, the codon optimization processes are different among different providers and are often hidden from the users. Here, the d'Hondt method, which is widely adopted as a method for determining the number of seats for each party in proportional-representation public elections, is applied to RSCU fitting. This allowed me to make a set of electronic spreadsheets for manual design of protein coding sequences for expression in Escherichia coli, with which users can see the process of codon optimization and can manually edit the codons after the automatic optimization. The spreadsheets may also be useful for molecular biology education. PMID:27002987

  20. Eukaryotic Evolutionary Transitions Are Associated with Extreme Codon Bias in Functionally-Related Proteins

    PubMed Central

    Hudson, Nicholas J.; Gu, Quan; Nagaraj, Shivashankar H.; Ding, Yong-Sheng; Dalrymple, Brian P.; Reverter, Antonio

    2011-01-01

    Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins – perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair – a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function – which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins – perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor – which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation. PMID:21966531

  1. Transcription attenuation in Salmonella typhimurium: the significance of rare leucine codons in the leu leader.

    PubMed Central

    Carter, P W; Bartkus, J M; Calvo, J M

    1986-01-01

    The leucine operon of Salmonella typhimurium is controlled by a transcription attenuation mechanism. Four adjacent leucine codons within a 160-nucleotide leu leader RNA are thought to play a central role in this mechanism. Three of the four codons are CUA, a rarely used leucine codon within enteric bacteria. To determine whether the nature of the leucine codon affects the regulation of the leucine operon, we used oligonucleotide-directed mutagenesis to first convert one CUA of the leader to CUG and then convert all three CUA codons to CUG. CUG is the most frequently used leucine codon in enteric bacteria. A mutant having (CUA)2CUGCUC in place of (CUA)3CUC has an altered response to leucine limitation, requiring a slightly higher degree of limitation to effect derepression. Changing (CUA)3CUC to (CUG)3CUC has more dramatic effects upon operon expression. First, the basal level of expression is lowered to the point that the mutant grows more slowly than the parent in a minimal medium lacking leucine. Second, the response of the mutant to a leucine limitation is dramatically altered such that even a strong limitation elicits only a modest degree of derepression. If the mutant is grown under conditions of leucyl-tRNA limitation rather than leucine limitation, complete derepression can be achieved, but only at a much higher degree of limitation than for the wild-type operon. These results provide a clear-cut example of codon usage having a dramatic effect upon gene expression. PMID:3534884

  2. Pattern of antimicrobial usage in livestock animals in south-western Nigeria: The need for alternative plans.

    PubMed

    Adesokan, Hezekiah K; Akanbi, IfeOluwapo O; Akanbi, Ibikunle M; Obaweda, Ruth A

    2015-01-01

    Resistance to antibiotics has continued to increase, placing future animal and human disease management in real danger. The developing countries characterised by widespread indiscriminate antibiotic use and in which 'third-generation' antibiotics are not readily available or affordable are the worst affected. A 3-year (2010-2012) retrospective survey of antibiotic usage in livestock production in three selected states of south-western Nigeria was conducted. Data obtained from eight purposively selected licensed veterinary pharmaceutical sales establishments in the area, based on keeping detailed sales records for the study period, were analysed using Stata Version 12. Results showed that tetracyclines (33.6%), fluoroquinolones (26.5%) and beta-lactams/aminoglycosides (20.4%) constituted the majority of the antibiotics used over the 3 years. The differences in the quantities of antibiotic types used within each antimicrobial class were statistically significant for tetracyclines (F = 59.87; p < 0.0001) and fluoroquinolones (F = 43.97; p < 0.0001) but not for beta-lactams/aminoglycosides (F = 3.21; p = 0.148). Furthermore, antibiotic consumption increased by 40.4% between 2010 and 2012. Although statistically insignificant (F = 0.277; p = 0.762), the increasing trend across the years was at rates of 23.5% between 2010 and 2011 and 13.8% between 2011 and 2012. In addition, the findings show a significantly higher consumption rate (t = 15.21; df = 5; p < 0.0001) during the rainy (52.5%) than the dry (47.5%) seasons. The current increasing trend in antibiotic usage holds a serious danger for the future and therefore calls for alternative plans to safeguard future livestock production, food security and human health. This becomes more imperative considering emerging resistance against tetracyclines and fluoroquinolones, the foremost remedies for livestock diseases in most developing countries. PMID:26016985

  3. Usage Pattern and Serum Level Measurement of Amikacin in the Internal Medicine Ward of the Largest Referral Hospital in the South of Iran: A Pharmacoepidemiological Study

    PubMed Central

    Namazi, Soha; Sagheb, Mohammad Mahdi; Hashempour, Mohammad Mahdi; Sadatsharifi, Arman

    2016-01-01

    Background: The inappropriate use of aminoglycosides has harmful effects such as the development of resistant pathogens and the incidence of nephrotoxicity and ototoxicity. Therefore, drug utilization evaluation of these drugs may improve their usage remarkably. The aim of this study was to assess the usage pattern of amikacin in an internal medicine ward. Methods: This cross-sectional study was conducted in the Internal Medicine Ward of Nemazee Teaching Hospital, Shiraz, Iran, in 2011. The guideline for amikacin use was approved by the institutional Pharmacy and Therapeutics Committee, and the study criteria were developed to assess several parameters involved in amikacin therapy such as appropriateness of drug use, dosage, duration of therapy, toxicity monitoring, and serum concentration assay. Serum concentration was assayed using a Cobas Mira AutoAnalyzer. Clinical and paraclinical parameters such as glomerular filtration rate, culture, microbial sensitivity, white blood cell count, and fever were collected. Results: Sixty-three patients were evaluated. Fifty-seven percent of the patients needed dose readjustment; however, it was not performed for 89% of them. Culture between 48 and 72 hours after amikacin administration was not controlled for 79% of the patients. In 19% of the patients, optimum therapeutic effect was not achieved. The mean±SD of the trough and peak concentrations was 7.63±5.4 μg/mL and 15.67±7.79 μg/mL, respectively. Forty-five percent of the trough and 38% of the peak levels were within the therapeutic range. The overall adherence of amikacin usage to the guideline was only 48%. Conclusion: To achieve appropriate treatment and prevent toxic effects, we recommend that pharmacokinetic dosing methods, amikacin guideline, and serum monitoring be considered. PMID:27217603

  4. A theoretical analysis of codon adaptation index of the Boophilus microplus bm86 gene directed to the optimization of a DNA vaccine.

    PubMed

    Ruiz, Lina María; Armengol, Gemma; Habeych, Edwin; Orduz, Sergio

    2006-04-21

    DNA vaccines utilize host cell molecules for gene transcription and translation to proteins, and the interspecific difference of codon usage is one of the major obstacles for effective induction of specific and strong immune response. In an attempt to improve codon usage effects of DNA vaccine on protein expression, a quantitative study was conducted to clarify the relationship of codon usage in the tick gene bm86 and its potential expression in bovine cells. The calculated relative synonymous codon usage (RSCU) and codon adaptation index (CAI) values of bm86 from Boophilus microplus and a set of 14 highly expressed genes from Bos taurus indicated that some codons utilized frequently in bm86 are rarely used in B. taurus genes and vice versa. The different translational efficiencies obtained suggested that after DNA vaccination using the wild bm86 gene, the protein Bm86 would be expressed in bovines, but it would not be the optimum sequence. However, using the codon-optimized bm86 gene to bovines, whose sequence was theoretically designed, would probably improve the level of the immune response generated against ticks. PMID:16171828

  5. Entertainment or Health? Exploring the Internet Usage Patterns of the Urban Poor: A Secondary Analysis of a Randomized Controlled Trial

    PubMed Central

    Okechukwu, Cassandra A; Sorensen, Glorian; Viswanath, Kasisomayajula

    2016-01-01

    Background Important gaps remain in our knowledge of how individuals from low socioeconomic position (SEP) use the Internet for resources and in understanding the full range of activities they perform online. Although self-report data indicate that low SEP individuals use the Internet less than high SEP people for health information and for other beneficial capital-enhancing activities, these results may not provide an accurate overall view of online use. Objective The aim of this study was to determine the ways in which low SEP individuals use the Internet, including for entertainment, social networking, and capital-enhancing functions, and how they are associated with health information seeking. Methods Detailed Web tracking data were collected from 118 low SEP individuals who participated in the intervention group of a randomized controlled trial that provided Internet access. Websites were grouped by topic, including categories of capital-enhancing websites that provided access to resources and information. Different types of online activities were summed into an Internet use index. Single and multiple negative binomial regression models were fitted with the Internet use index as the predictor and health information seeking as the outcome. Next, models were fitted with low, medium, and high Web usage in capital-enhancing, entertainment, and social network categories to determine their associations with health information seeking. Results Participants used the Web for diverse purposes, with 63.6% (75/118) accessing the Internet for all defined types of Internet use. Each additional category of Internet use was associated with 2.12 times the rate of health information seeking (95% CI 1.84-2.44, P<.001). Higher use of each type of capital-enhancing information was associated with higher rates of health information seeking, with high uses of government (incident rate ratio [IRR] 8.90, 95% CI 4.82-16.42, P<.001) and news (IRR 11.36, 95% CI 6.21-20.79, P<.001

  6. Usage patterns of biomarkers in non-small-cell lung cancer patients in India: Findings from a systematic review and survey

    PubMed Central

    Desai, Chirag; Mehta, Anurag; Mishra, Divya

    2014-01-01

    Introduction: Personalized medicine has facilitated improved management of non-small cell lung cancer (NSCLC) patients by identifying predictive and prognostic biomarkers for enhanced efficiency of detection and efficacy of treatment. This systematic review and survey assessed the patterns of biomarker usage, molecular testing techniques to diagnose patients with NSCLC in India and testing techniques recommended by cancer societies. Materials and Methods: Studies were retrieved from Embase, PubMed, and Cochrane databases for the last 12 years, using relevant search strategies as per the Cochrane methodology for systematic reviews. Outcomes of interest were biomarkers for NSCLC, patterns of biomarker testing, diagnostic methods, guidelines and cost of biomarker testing. Results: In all, 499 studies were identified for screening and 17 primary publications were included in the review. Epidermal growth factor receptor (EGFR) expression and epithelial markers (particularly cytokeratins (CK)) were the most commonly reported biomarkers (7/17) and immunohistochemical (IHC) staining was the most common technique for detection of biomarkers. The frequency of EGFR mutations was higher among women than men. Significantly elevated levels of CK-18 were observed in patients with squamous cell carcinoma and of CK-19 in patients with adenocarcinoma, squamous cell carcinoma, and NSCLC (P < 0.001). Prognostic or predictive role of cytokines and angiogenic markers as well as DNA expression were evaluated. The survey also showed that IHC was the most common technique for detection of biomarkers. Conclusions: This systematic review and survey provides valuable information on biomarker usage in the Indian population, and highlights the need for initiatives required for future biomarker testing in India. PMID:25125812

  7. Codon preferences in free-living microorganisms.

    PubMed Central

    Andersson, S G; Kurland, C G

    1990-01-01

    A popular interpretation of the major codon preference is that it reflects the operation of a regulatory device that controls the expression of individual proteins. In this popular model, rapidly translated codons are thought to promote the accumulation of the highly expressed proteins and slowly translated codons are thought to retard the expression of poorly expressed proteins. However, this widely accepted model is not supported by kinetic theory or by experimental results. A less fashionable model in which the major codon preference has nothing to do with the expression level of the individual proteins is forwarded. In this model, the major codon preference is viewed as a global strategy to support the efficient function of the translation system and thereby to maximize the growth rates of cells under favorable conditions. PMID:2194095

  8. Codon information value and codon transition-probability distributions in short-term evolution

    NASA Astrophysics Data System (ADS)

    Jiménez-Montaño, M. A.; Coronel-Brizio, H. F.; Hernández-Montoya, A. R.; Ramos-Fernández, A.

    2016-07-01

    To understand the way the Genetic Code and the physical-chemical properties of coded amino acids affect accepted amino acid substitutions in short-term protein evolution, taking into account only overall amino acid conservation, we consider an underlying codon-level model. This model employs codon pair-substitution frequencies from an empirical matrix in the literature, modified for single-base mutations only. Ordering the degenerated codons according to their codon information value (Volkenstein, 1979), we found that three-fold and most of four-fold degenerated codons, which have low codon values, were best fitted to rank-frequency distributions with constant failure rate (exponentials). In contrast, almost all two-fold degenerated codons, which have high codon values, were best fitted to rank-frequency distributions with variable failure rate (inverse power-laws). Six-fold degenerated codons are considered to be doubly assigned. The exceptional behavior of some codons, including non-degenerate codons, is discussed.

  9. CodonPhyML: Fast Maximum Likelihood Phylogeny Estimation under Codon Substitution Models

    PubMed Central

    Gil, Manuel; Zoller, Stefan; Anisimova, Maria

    2013-01-01

    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. PMID:23436912

  10. Comparing Usage Patterns Recorded between an Electronic Reference and an Electronic Monograph Collection: The Differences in Searches and Full-Text Content Viewings

    ERIC Educational Resources Information Center

    Lamothe, Alain R.

    2012-01-01

    This paper presents the results from a quantitative and systematic analysis comparing the online usage of an e-reference and an e-monograph collection. A very strong relationship exists between size and usage: the larger the collection, the greater the usage. An equally strong relationship exists between searches and viewings, meaning that the…

  11. The Relationship between the Perceived Threat of Various Substances to Patterns of Non-Usage Behavior--Implications for Health Education.

    ERIC Educational Resources Information Center

    O'Rourke, Thomas W.; Martin, Gary L.

    The purpose of this investigation was to determine the relationship between the perceived health threat of various substances and the non-usage of such substances. It was hypothesized that non-usage behavior is related to the perceived health threat of a substance upon the individual. Specifically, non-usage increases as the perceived threat…

  12. A model of protein translation including codon bias, nonsense errors, and ribosome recycling.

    PubMed

    Gilchrist, Michael A; Wagner, Andreas

    2006-04-21

    We present and analyse a model of protein translation at the scale of an individual messenger RNA (mRNA) transcript. The model we develop is unique in that it incorporates the phenomena of ribosome recycling and nonsense errors. The model conceptualizes translation as a probabilistic wave of ribosome occupancy traveling down a heterogeneous medium, the mRNA transcript. Our results show that the heterogeneity of the codon translation rates along the mRNA results in short-scale spikes and dips in the wave. Nonsense errors attenuate this wave on a longer scale while ribosome recycling reinforces it. We find that the combination of nonsense errors and codon usage bias can have a large effect on the probability that a ribosome will completely translate a transcript. We also elucidate how these forces interact with ribosome recycling to determine the overall translation rate of an mRNA transcript. We derive a simple cost function for nonsense errors using our model and apply this function to the yeast (Saccharomyces cervisiae) genome. Using this function we are able to detect position dependent selection on codon bias which correlates with gene expression levels as predicted a priori. These results indirectly validate our underlying model assumptions and confirm that nonsense errors can play an important role in shaping codon usage bias. PMID:16171830

  13. Codon influence on protein expression in E. coli correlates with mRNA levels.

    PubMed

    Boël, Grégory; Letso, Reka; Neely, Helen; Price, W Nicholson; Wong, Kam-Ho; Su, Min; Luff, Jon D; Valecha, Mayank; Everett, John K; Acton, Thomas B; Xiao, Rong; Montelione, Gaetano T; Aalberts, Daniel P; Hunt, John F

    2016-01-21

    Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli. PMID:26760206

  14. E-CAI: a novel server to estimate an expected value of Codon Adaptation Index (eCAI)

    PubMed Central

    Puigbò, Pere; Bravo, Ignacio G; Garcia-Vallvé, Santiago

    2008-01-01

    Background The Codon Adaptation Index (CAI) is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values. Results The E-CAI server, available at , is a web-application that calculates an expected value of CAI for a set of query sequences by generating random sequences with G+C and amino acid content similar to those of the input. An executable file, a tutorial, a Frequently Asked Questions (FAQ) section and several examples are also available. To exemplify the use of the E-CAI server, we have analysed the codon adaptation of human mitochondrial genes that codify a subunit of the mitochondrial respiratory chain (excluding those genes that lack a prokaryotic orthologue) and are encoded in the nuclear genome. It is assumed that these genes were transferred from the proto-mitochondrial to the nuclear genome and that its codon usage was then ameliorated. Conclusion The E-CAI server provides a direct threshold value for discerning whether the differences in CAI are statistically significant or whether they are merely artifacts that arise from internal biases in the G+C composition and/or amino acid composition of the query sequences. PMID:18230160

  15. The most deviated codon position in AT-rich bacterial genomes: a function related analysis.

    PubMed

    Ma, Bin-Guang; Chen, Ling-Ling

    2005-10-01

    We have performed systematic study on more than 120 archaeal and bacterial genomes. Based on the index proposed in the current paper, clear patterns are observed showing the relation between the base compositional deviation at three codon positions and the genomic GC content. For AT-rich genomes, the Most Deviated Codon Position (MDCP) is the 1st codon position, while for GC-rich genomes, MDCP appears at the 2nd or 3rd codon position alternatively. According to MDCP, the CDSs of a genome can be classified into two types: typical and atypical. In AT-rich genomes the typical represent the majority and account for about 3/4 of all the CDSs. Based on the functional classification of COG database, the two types of CDSs are examined. An apparent bias of distribution is observed that the CDSs with the function of 'information processing' are more likely to present in typical type. PMID:16060688

  16. Mutations to Less-Preferred Synonymous Codons in a Highly Expressed Gene of Escherichia coli: Fitness and Epistatic Interactions.

    PubMed

    Hauber, David J; Grogan, Dennis W; DeBry, Ronald W

    2016-01-01

    Codon-tRNA coevolution to maximize protein production has been, until recently, the dominant hypothesis to explain codon-usage bias in highly expressed bacterial genes. Two predictions of this hypothesis are 1) selection is weak; and 2) similar silent replacements at different codons should have similar fitness consequence. We used an allele-replacement strategy to change five specific 3rd-codon-position (silent) sites in the highly expressed Escherichia coli ribosomal protein gene rplQ from the wild type to a less-preferred alternative. We introduced the five mutations within a 10-codon region. Four of the silent sites were chosen to test the second prediction, with a CTG to CTA mutation being introduced at two closely linked leucine codons and an AAA to AAG mutation being introduced at two closely linked lysine codons. We also introduced a fifth silent mutation, a GTG to GTA mutation at a valine codon in the same genic region. We measured the fitness effect of the individual mutations by competing each single-mutant strain against the parental wild-type strain, using a disrupted form of the araA gene as a selectively neutral phenotypic marker to distinguish between strains in direct competition experiments. Three of the silent mutations had a fitness effect of |s| > 0.02, which is contradictory to the prediction that selection will be weak. The two leucine mutations had significantly different fitness effects, as did the two lysine mutations, contradictory to the prediction that similar mutations at different codons should have similar fitness effects. We also constructed a strain carrying all five silent mutations in combination. Its fitness effect was greater than that predicted from the individual fitness values, suggesting that negative synergistic epistasis acts on the combination allele. PMID:26727272

  17. Mutations to Less-Preferred Synonymous Codons in a Highly Expressed Gene of Escherichia coli: Fitness and Epistatic Interactions

    PubMed Central

    Hauber, David J.; Grogan, Dennis W.; DeBry, Ronald W.

    2016-01-01

    Codon-tRNA coevolution to maximize protein production has been, until recently, the dominant hypothesis to explain codon-usage bias in highly expressed bacterial genes. Two predictions of this hypothesis are 1) selection is weak; and 2) similar silent replacements at different codons should have similar fitness consequence. We used an allele-replacement strategy to change five specific 3rd-codon-position (silent) sites in the highly expressed Escherichia coli ribosomal protein gene rplQ from the wild type to a less-preferred alternative. We introduced the five mutations within a 10-codon region. Four of the silent sites were chosen to test the second prediction, with a CTG to CTA mutation being introduced at two closely linked leucine codons and an AAA to AAG mutation being introduced at two closely linked lysine codons. We also introduced a fifth silent mutation, a GTG to GTA mutation at a valine codon in the same genic region. We measured the fitness effect of the individual mutations by competing each single-mutant strain against the parental wild-type strain, using a disrupted form of the araA gene as a selectively neutral phenotypic marker to distinguish between strains in direct competition experiments. Three of the silent mutations had a fitness effect of |s| > 0.02, which is contradictory to the prediction that selection will be weak. The two leucine mutations had significantly different fitness effects, as did the two lysine mutations, contradictory to the prediction that similar mutations at different codons should have similar fitness effects. We also constructed a strain carrying all five silent mutations in combination. Its fitness effect was greater than that predicted from the individual fitness values, suggesting that negative synergistic epistasis acts on the combination allele. PMID:26727272

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

    PubMed Central

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

    2009-01-01

    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

  19. 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

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

    2002-06-01

    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, SVM(light). 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. PMID:12034849

  20. Seat Belt Usage in Injured Car Occupants: Injury Patterns, Severity and Outcome After Two Main Car Accident Mechanisms in Kashan, Iran, 2012

    PubMed Central

    Mohammadzadeh, Mahdi; Paravar, Mohammad; Mirzadeh, Azadeh Sadat; Mohammadzadeh, Javad; Mahdian, Soroush

    2015-01-01

    Background: Road traffic accidents (RTAs) are the main public health problems in Iran. The seat belts, which are vehicle safety devices, are imperative to reduce the risk of severe injuries and mortality. Objectives: The aim of the study was to evaluate injury patterns, severity and outcome among belted and unbelted car occupants who were injured in car accidents. Patients and Methods: This cross-sectional prospective study was performed on all car occupants injured in RTAs (n = 822) who were transported to hospital and hospitalized for more than 24 hours from March 2012 to March 2013. Demographic profile of the patients, including age, gender, position in the vehicle, the use of seat belts, type of car crashes, injured body regions, revised trauma score (RTS), Glasgow coma score (GCS), duration of hospital stay and mortality rate were analyzed by descriptive analysis, chi-square and independent t-test. P < 0.05 was considered significant. Results: A total of 560 patients used seat belts (68.1%). The unbelted occupants were younger (28 years vs. 38 years) and had more frequently sustained head, abdomen and multiple injuries (P = 0.01, P = 0.01 and P = 0.009, respectively). Also, these patients had significantly lower GCS and elongated hospitalization and higher death rate (P = 0.001, P = 0.001 and P = 0.05, respectively). Tendency of severe head trauma and low RTS and death were increased in unbelted occupants in car rollover accident mechanisms (P = 0.001, P = 0.01 and P = 0.008, respectively). Conclusions: During car crashes, especially car rollover, unbelted occupants are more likely to sustain multiple severe injuries and death. Law enforcement of the seat belt usage for all occupants (front and rear seat) is obligatory to reduce severe injuries sustained as a result of car accidents, especially in vehicles with low safety. PMID:26064867

  1. Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases, 2007 vs 2012: findings from a large US healthcare claims database analysis.

    PubMed

    Weng, W; Liang, Y; Kimball, E S; Hobbs, T; Kong, S; Sakurada, B; Bouchard, J

    2016-07-01

    Objective To explore trends in demographics, comorbidities, anti-diabetic drug usage, and healthcare utilization costs in patients with newly-diagnosed type 2 diabetes mellitus (T2DM) using a large US claims database. Methods For the years 2007 and 2012, Truven Health Marketscan Research Databases were used to identify adults with newly-diagnosed T2DM and continuous 12-month enrollment with prescription benefits. Variables examined included patient demographics, comorbidities, inpatient utilization patterns, healthcare costs (inpatient and outpatient), drug costs, and diabetes drug claim patterns. Results Despite an increase in the overall database population between 2007-2012, the incidence of newly-diagnosed T2DM decreased from 1.1% (2007) to 0.65% (2012). Hyperlipidemia and hypertension were the most common comorbidities and increased in prevalence from 2007 to 2012. In 2007, 48.3% of newly-diagnosed T2DM patients had no claims for diabetes medications, compared with 36.2% of patients in 2012. The use of a single oral anti-diabetic drug (OAD) was the most common diabetes medication-related claim (46.2% of patients in 2007; 56.7% of patients in 2012). Among OAD monotherapy users, metformin was the most commonly used and increased from 2007 (74.7% of OAD monotherapy users) to 2012 (90.8%). Decreases were observed for sulfonylureas (14.1% to 6.2%) and thiazolidinediones (7.3% to 0.6%). Insulin, predominantly basal insulin, was used by 3.9% of patients in 2007 and 5.3% of patients in 2012. Mean total annual healthcare costs increased from $13,744 in 2007 to $15,175 in 2012, driven largely by outpatient services, although costs in all individual categories of healthcare services (inpatient and outpatient) increased. Conversely, total drug costs per patient were lower in 2012 compared with 2007. Conclusions Despite a drop in the rate of newly-diagnosed T2DM from 2007 to 2012 in the US, increased total medical costs and comorbidities per individual patient suggest that

  2. Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius

    PubMed Central

    Johnston, Christopher D.; Bannantine, John P.; Govender, Rodney; Endersen, Lorraine; Pletzer, Daniel; Weingart, Helge; Coffey, Aidan; O'Mahony, Jim; Sleator, Roy D.

    2014-01-01

    It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants were preserved in synthetic MMP proteins as shown by monoclonal antibody mediated ELISA. Moreover, MMP is a membrane protein in MAP, which is also targeted to the cellular surface of recombinant L. salivarius at levels comparable to MAP. Additionally, we previously engineered MAP3733c (encoding MptD) and show herein that MptD displays the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adheres to the MptD-specific bacteriophage fMptD. This work demonstrates there is potential for L. salivarius as a viable antigen delivery vehicle for MAP, which may provide an effective mucosal vaccine against Johne's disease. PMID:25237653

  3. Participants, Usage, and Use Patterns of a Web-Based Intervention for the Prevention of Depression Within a Randomized Controlled Trial

    PubMed Central

    Bohlmeijer, Ernst T; Van Gemert-Pijnen, Julia EWC

    2013-01-01

    Background Although Web-based interventions have been shown to be effective, they are not widely implemented in regular care. Nonadherence (ie, participants not following the intervention protocol) is an issue. By studying the way Web-based interventions are used and whether there are differences between adherers (ie, participants that started all 9 lessons) and nonadherers, more insight can be gained into the process of adherence. Objective The aims of this study were to (1) describe the characteristics of participants and investigate their relationship with adherence, (2) investigate the utilization of the different features of the intervention and possible differences between adherers and nonadherers, and (3) identify what use patterns emerge and whether there are differences between adherers and nonadherers. Methods Data were used from 206 participants that used the Web-based intervention Living to the full, a Web-based intervention for the prevention of depression employing both a fully automated and human-supported format. Demographic and baseline characteristics of participants were collected by using an online survey. Log data were collected within the Web-based intervention itself. Both quantitative and qualitative analyses were performed. Results In all, 118 participants fully adhered to the intervention (ie, started all 9 lessons). Participants with an ethnicity other than Dutch were more often adherers (χ2 1=5.5, P=.02), and nonadherers used the Internet more hours per day on average (F1,203=3.918, P=.049). A logistic regression showed that being female (OR 2.02, 95% CI 1.01-4.04; P=.046) and having a higher need for cognition (OR 1.02; 95% CI 1.00-1.05; P=.02) increased the odds of adhering to the intervention. Overall, participants logged in an average of 4 times per lesson, but adherers logged in significantly more times per lesson than nonadherers (F1,204=20.710; P<.001). For use patterns, we saw that early nonadherers seemed to use fewer sessions

  4. Key for protein coding sequences identification: computer analysis of codon strategy.

    PubMed Central

    Rodier, F; Gabarro-Arpa, J; Ehrlich, R; Reiss, C

    1982-01-01

    The signal qualifying an AUG or GUG as an initiator in mRNAs processed by E. coli ribosomes is not found to be a systematic, literal homology sequence. In contrast, stability analysis reveals that initiators always occur within nucleic acid domains of low stability, for which a high A/U content is observed. Since no aminoacid selection pressure can be detected at N-termini of the proteins, the A/U enrichment results from a biased usage of the code degeneracy. A computer analysis is presented which allows easy detection of the codon strategy. N-terminal codons carry rather systematically A or U in third position, which suggests a mechanism for translation initiation and helps to detect protein coding sequences in sequenced DNA. PMID:7038623

  5. Usage pattern-based exposure screening as a simple tool for the regional priority-setting in environmental risk assessment of veterinary antibiotics: a case study of north-western Germany.

    PubMed

    Menz, J; Schneider, M; Kümmerer, K

    2015-05-01

    Veterinary antibiotics (VAs) are widely recognized as important environmental contaminants. Despite the extensive use of antibiotic agents in meat and poultry production and the known resistance problems in human and veterinary medicine, detailed knowledge about usage patterns of VAs in Germany is still scarce. This lack of knowledge severely impacts current research on the environmental risk of VAs, but it is expected that recently established surveillance programs for antimicrobial drug usage will close this knowledge gap. Therefore, a spatially more precise environmental risk assessment and management might become possible in the near future. In this study, a new usage pattern-based exposure screening (UPES) approach for the comprehensive environmental exposure assessment of veterinary antibiotics was preliminarily assessed using approximated scenarios of antimicrobial substance usage in German meat and poultry production. Resulting predicted manure concentrations covered seven orders of magnitude ranging from ng kg(-1) to g kg(-1) dry weight (dw). Beyond that 14 antibiotic substances of 10 different antimicrobial classes were predicted to have the potential to occur in soil concentrations higher than 100 μg kg(-1) dw. These findings raise further questions regarding the environmental exposure and risks of frequently used VAs, especially in regions with higher-than-average livestock density. With this case study we demonstrate that UPES simplifies to account for differing local agricultural factors and therefore facilitates priority-setting on a regional level. In this context a simple prioritization scheme for environmental assessment of VAs, considering both the expected environmental concentration and the frequency of application, is proposed in this paper. PMID:25655696

  6. Saccharomyces cerevisiae ribosomes recognize non-AUG initiation codons.

    PubMed Central

    Zitomer, R S; Walthall, D A; Rymond, B C; Hollenberg, C P

    1984-01-01

    A series of Saccharomyces cerevisiae plasmids and mutant derivatives containing fusions of the Escherichia coli galactokinase gene, galK, to the yeast iso-1-cytochrome c CYC1 transcription unit were used to study the sequences affecting the initiation of translation in S. cerevisiae. When the CYC1 AUG initiation codon preceded the galK AUG codon and coding sequence and either the two AUGs were out of frame with each other or a nonsense codon was located between them, the expression of the galK gene was extremely low. Deletion of the CYC1 AUG and its surrounding sequences resulted in a 100-fold increase in galK expression. This dependence of galK expression on the elimination of the CYC1 AUG codon was used to select mutations in that codon. Then the ability of these altered initiation codons to serve in translational initiation was determined by reconstruction of the CYC1 gene 3' to and in frame with them. Initiation was found to occur at the codons UUG and AUA, but not at the codons AAA and AUC. Furthermore the codon UUG, when preceded by an A three nucleotides upstream, served as a better initiation codon than when a U was substituted for the A. The efficiency of translation from these non-AUG codons was quantitated by using a CYC1/galK protein-coding fusion and measuring cellular galactokinase levels. Initiation at the UUG codon was 6.9% as efficient as initiation at the wild-type AUG codon when preceded by an A three nucleotides upstream, but was over 10-fold less efficient when a U was substituted for that A. Initiation at AUA was 0.5% as efficient as at AUG. The effects of the sequences preceding the initiation codon are discussed in light of these results. PMID:6390186

  7. Impact of rare codons and the functional coproduction of rate-limiting tRNAs on recombinant protein production in Bacillus megaterium.

    PubMed

    Finger, Constanze; Gamer, Martin; Klunkelfuß, Saskia; Bunk, Boyke; Biedendieck, Rebekka

    2015-11-01

    The Gram-positive bacterium Bacillus megaterium was systematically developed for the plasmid-based production of recombinant proteins at the gram-per-liter scale. The amount of protein produced per cell was found strongly correlated to the codon usage of the heterologous gene of interest in comparison to the codon usage of B. megaterium. For analyzing the influence of rare codons on the translational efficiency and protein production in B. megaterium, a test system using the gene for the green fluorescent protein (GFP) as reporter was established. For this purpose, four consecutive identical codons were introduced into the 5' end of gfp and the resulting variations in GFP formation were quantified. Introduction of the rare codons GCC, CGG, and ACC for alanine, arginine, and threonine reduced GFP production 2.1-, 3.3-, and 1.7-fold in comparison to the favored codons GCU, CGU, and ACA, respectively. Coexpression of the corresponding rare codon tRNA (rctRNA) genes improved GFP production 4.2-, 2.7-, and 1.7-fold, respectively. The system was applied to the production of a formate dehydrogenase (FDH) from Mycobacterium vaccae and an extracellular hydrolase (TFH) from Thermobifida fusca. Coexpression of one to three different rctRNA genes resulted in an up to 18-fold increased protein production. Interestingly, rctRNA gene coexpression also elevated the production of M. vaccae FDH and T. fusca TFH from codon optimized genes, indicating a general positive effect by rctRNA gene overexpression on the protein production in B. megaterium. Thus, the basis for a B. megaterium enhanced production strain coexpressing rctRNA genes was laid. PMID:26138251

  8. Evaluating Sense Codon Reassignment with a Simple Fluorescence Screen.

    PubMed

    Biddle, Wil; Schmitt, Margaret A; Fisk, John D

    2015-12-22

    Understanding the interactions that drive the fidelity of the genetic code and the limits to which modifications can be made without breaking the translational system has practical implications for understanding the molecular mechanisms of evolution as well as expanding the set of encodable amino acids, particularly those with chemistries not provided by Nature. Because 61 sense codons encode 20 amino acids, reassigning the meaning of sense codons provides an avenue for biosynthetic modification of proteins, furthering both fundamental and applied biochemical research. We developed a simple screen that exploits the absolute requirement for fluorescence of an active site tyrosine in green fluorescent protein (GFP) to probe the pliability of the degeneracy of the genetic code. Our screen monitors the restoration of the fluorophore of GFP by incorporation of a tyrosine in response to a sense codon typically assigned another meaning in the genetic code. We evaluated sense codon reassignment at four of the 21 sense codons read through wobble interactions in Escherichia coli using the Methanocaldococcus jannaschii orthogonal tRNA/aminoacyl tRNA synthetase pair originally developed and commonly used for amber stop codon suppression. By changing only the anticodon of the orthogonal tRNA, we achieved sense codon reassignment efficiencies between 1% (Phe UUU) and 6% (Lys AAG). Each of the orthogonal tRNAs preferentially decoded the codon traditionally read via a wobble interaction in E. coli with the exception of the orthogonal tRNA with an AUG anticodon, which incorporated tyrosine in response to both the His CAU and His CAC codons with approximately equal frequencies. We applied our screen in a high-throughput manner to evaluate a 10(9)-member combined tRNA/aminoacyl tRNA synthetase library to identify improved sense codon reassigning variants for the Lys AAG codon. A single rapid screen with the ability to broadly evaluate reassignable codons will facilitate

  9. The surprising negative correlation of gene length and optimal codon use - disentangling translational selection from GC-biased gene conversion in yeast

    PubMed Central

    2011-01-01

    Background Surprisingly, in several multi-cellular eukaryotes optimal codon use correlates negatively with gene length. This contrasts with the expectation under selection for translational accuracy. While suggested explanations focus on variation in strength and efficiency of translational selection, it has rarely been noticed that the negative correlation is reported only in organisms whose optimal codons are biased towards codons that end with G or C (-GC). This raises the question whether forces that affect base composition - such as GC-biased gene conversion - contribute to the negative correlation between optimal codon use and gene length. Results Yeast is a good organism to study this as equal numbers of optimal codons end in -GC and -AT and one may hence compare frequencies of optimal GC- with optimal AT-ending codons to disentangle the forces. Results of this study demonstrate in yeast frequencies of GC-ending (optimal AND non-optimal) codons decrease with gene length and increase with recombination. A decrease of GC-ending codons along genes contributes to the negative correlation with gene length. Correlations with recombination and gene expression differentiate between GC-ending and optimal codons, and also substitution patterns support effects of GC-biased gene conversion. Conclusion While the general effect of GC-biased gene conversion is well known, the negative correlation of optimal codon use with gene length has not been considered in this context before. Initiation of gene conversion events in promoter regions and the presence of a gene conversion gradient most likely explain the observed decrease of GC-ending codons with gene length and gene position. PMID:21481245

  10. Kinetics of Stop Codon Recognition by Release Factor 1

    PubMed Central

    Hetrick, Byron; Lee, Kristin; Joseph, Simpson

    2009-01-01

    Recognition of stop codons by class I release factors is a fundamental step in the termination phase of protein synthesis. Since premature termination is costly to the cell, release factors have to efficiently discriminate between stop and sense codons. In order to understand the mechanism of discrimination between stop and sense codons, we developed a new, pre-steady state kinetic assay to monitor the interaction of RF1 with the ribosome. Our results show that RF1 associates with similar association rate constants to ribosomes programmed with a stop or sense codons. However, dissociation of RF1 from sense codons is as much as three orders of magnitude faster than from stop codons. Interestingly, the affinity of RF1 for ribosomes programmed with different sense codons does not correlate with the defects in peptide release. Thus, discrimination against sense codons is achieved, both, by increasing the dissociation rates and by decreasing the rate of peptide release. These results suggest that sense codons inhibit conformational changes necessary for RF1 to stably bind to the ribosome and catalyze peptide release. PMID:19874047

  11. A computer program to display codon changes caused by mutagenesis.

    PubMed

    Sirotkin, K

    1988-04-01

    A FORTRAN program for displaying the correspondence between codon changes and different possible base changes is presented. Changes of both single bases and dimers are considered. The user can specify the mutagenesis spectrum. Additionally, the user can choose whether or not to consider single or double events in a codon and whether or not to consider the possibility that the change of two bases (a dimer) can overlap a codon boundary. Furthermore, a variety of ways may be chosen to display and summarize the codon changes that can result from the specified mutagenesis. A user-supplied sequence or the genetic code table can be analyzed. PMID:3167596

  12. Comparative context analysis of codon pairs on an ORFeome scale

    PubMed Central

    Moura, Gabriela; Pinheiro, Miguel; Silva, Raquel; Miranda, Isabel; Afreixo, Vera; Dias, Gaspar; Freitas, Adelaide; Oliveira, José L; Santos, Manuel AS

    2005-01-01

    Codon context is an important feature of gene primary structure that modulates mRNA decoding accuracy. We have developed an analytical software package and a graphical interface for comparative codon context analysis of all the open reading frames in a genome (the ORFeome). Using the complete ORFeome sequences of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Escherichia coli, we show that this methodology permits large-scale codon context comparisons and provides new insight on the rules that govern the evolution of codon-pair context. PMID:15774029

  13. Interfacial-tension-force model for the wavy stratified liquid-liquid flow pattern transition: The usage of two different approaches

    NASA Astrophysics Data System (ADS)

    de Castro, Marcelo Souza; Rodriguez, Oscar Mauricio Hernandez

    2016-06-01

    The study of the hydrodynamic stability of flow patterns is important in the design of equipment and pipelines for multiphase flows. The maintenance of a particular flow pattern becomes important in many applications, e.g., stratified flow pattern in heavy oil production avoiding the formation of emulsions because of the separation of phases and annular flow pattern in heat exchangers which increases the heat transfer coefficient. Flow maps are drawn to orientate engineers which flow pattern is present in a pipeline, for example. The ways how these flow maps are drawn have changed from totally experimental work, to phenomenological models, and then to stability analysis theories. In this work an experimental liquid-liquid flow map, with water and viscous oil as work fluids, drawn via subjective approach with high speed camera was used to compare to approaches of the same theory: the interfacial-tension-force model. This theory was used to drawn the wavy stratified flow pattern transition boundary. This paper presents a comparison between the two approaches of the interfacial-tension-force model for transition boundaries of liquid-liquid flow patterns: (i) solving the wave equation for the wave speed and using average values for wave number and wave speed; and (ii) solving the same equation for the wave number and then using a correlation for the wave speed. The results show that the second approach presents better results.

  14. Nonsense codons trigger an RNA partitioning shift.

    PubMed

    Bhalla, Angela D; Gudikote, Jayanthi P; Wang, Jun; Chan, Wai-Kin; Chang, Yao-Fu; Olivas, O Renee; Wilkinson, Miles F

    2009-02-13

    T-cell receptor-beta (TCRbeta) genes naturally acquire premature termination codons (PTCs) as a result of programmed gene rearrangements. PTC-bearing TCRbeta transcripts are dramatically down-regulated to protect T-cells from the deleterious effects of the truncated proteins that would otherwise be produced. Here we provide evidence that two responses collaborate to elicit this dramatic down-regulation. One is rapid mRNA decay triggered by the nonsense-mediated decay (NMD) RNA surveillance pathway. We demonstrate that this occurs in highly purified nuclei lacking detectable levels of three different cytoplasmic markers, but containing an outer nuclear membrane marker, suggesting that decay occurs either in the nucleoplasm or at the outer nuclear membrane. The second response is a dramatic partitioning shift in the nuclear fraction-to-cytoplasmic fraction mRNA ratio that results in few TCRbeta transcripts escaping to the cytoplasmic fraction of cells. Analysis of TCRbeta mRNA kinetics after either transcriptional repression or induction suggested that this nonsense codon-induced partitioning shift (NIPS) response is not the result of cytoplasmic NMD but instead reflects retention of PTC(+) TCRbeta mRNA in the nuclear fraction of cells. We identified TCRbeta sequences crucial for NIPS but found that NIPS is not exclusively a property of TCRbeta transcripts, and we identified non-TCRbeta sequences that elicit NIPS. RNA interference experiments indicated that NIPS depends on the NMD factors UPF1 and eIF4AIII but not the NMD factor UPF3B. We propose that NIPS collaborates with NMD to retain and degrade a subset of PTC(+) transcripts at the outer nuclear membrane and/or within the nucleoplasm. PMID:19091751

  15. Effect of codon-optimized E. coli signal peptides on recombinant Bacillus stearothermophilus maltogenic amylase periplasmic localization, yield and activity.

    PubMed

    Samant, Shalaka; Gupta, Gunja; Karthikeyan, Subbulakshmi; Haq, Saiful F; Nair, Ayyappan; Sambasivam, Ganesh; Sukumaran, Sunilkumar

    2014-09-01

    Recombinant proteins can be targeted to the Escherichia coli periplasm by fusing them to signal peptides. The popular pET vectors facilitate fusion of target proteins to the PelB signal. A systematic comparison of the PelB signal with native E. coli signal peptides for recombinant protein expression and periplasmic localization is not reported. We chose the Bacillus stearothermophilus maltogenic amylase (MA), an industrial enzyme widely used in the baking and brewing industry, as a model protein and analyzed the competence of seven, codon-optimized, E. coli signal sequences to translocate MA to the E. coli periplasm compared to PelB. MA fusions to three of the signals facilitated enhanced periplasmic localization of MA compared to the PelB fusion. Interestingly, these three fusions showed greatly improved MA yields and between 18- and 50-fold improved amylase activities compared to the PelB fusion. Previously, non-optimal codon usage in native E. coli signal peptide sequences has been reported to be important for protein stability and activity. Our results suggest that E. coli signal peptides with optimal codon usage could also be beneficial for heterologous protein secretion to the periplasm. Moreover, such fusions could even enhance activity rather than diminish it. This effect, to our knowledge has not been previously documented. In addition, the seven vector platform reported here could also be used as a screen to identify the best signal peptide partner for other recombinant targets of interest. PMID:25038884

  16. Structural basis for stop codon recognition in eukaryotes

    PubMed Central

    Murray, Jason; Hegde, Ramanujan S.; Ramakrishnan, V.

    2015-01-01

    Termination of protein synthesis occurs when a translating ribosome encounters one of three universally conserved stop codons: UGA, UAA, or UAG. Release factors recognise stop codons in the ribosomal A site to mediate release of the nascent chain and recycling of the ribosome. Bacteria decode stop codons using two separate release factors with differing specificities for the second and third bases1. By contrast, eukaryotes rely on an evolutionarily unrelated omnipotent release factor (eRF1) to recognise all three stop codons2. The molecular basis of eRF1 discrimination for stop codons over sense codons is not known. Here, we present electron cryo-microscopy (cryo-EM) structures at 3.5 – 3.8 Å resolution of mammalian ribosomal complexes containing eRF1 interacting with each of the three stop codons in the A site. Binding of eRF1 flips nucleotide A1825 of 18S rRNA so that it stacks on the second and third stop codon bases. This configuration pulls the fourth position base into the A site, where it is stabilised by stacking against G626 of 18S rRNA. Thus, eRF1 exploits two rRNA nucleotides also used during tRNA selection to drive mRNA compaction. Stop codons are favoured in this compacted mRNA conformation by a hydrogen-bonding network with essential eRF1 residues that constrains the identity of the bases. These results provide a molecular framework for eukaryotic stop codon recognition and have implications for future studies on the mechanisms of canonical and premature translation termination3,4. PMID:26245381

  17. AGRICULTURAL CHEMICAL USAGE DATA

    EPA Science Inventory

    This report, which summarizes the use of agricultural chemicals is issued by the National Agricultural Statistics Service (NASS) as part of its series on Agricultural Chemical Usage. Other publications in the series present statistics for on-farm agricultural chemical usage for f...

  18. Structural Basis for Translation Termination on a Pseudouridylated Stop Codon.

    PubMed

    Svidritskiy, Egor; Madireddy, Rohini; Korostelev, Andrei A

    2016-05-22

    Pseudouridylation of messenger RNA emerges as an abundant modification involved in gene expression regulation. Pseudouridylation of stop codons in eukaryotic and bacterial cells results in stop-codon read through. The structural mechanism of this phenomenon is not known. Here we present a 3.1-Å crystal structure of Escherichia coli release factor 1 (RF1) bound to the 70S ribosome in response to the ΨAA codon. The structure reveals that recognition of a modified stop codon does not differ from that of a canonical stop codon. Our in vitro biochemical results support this finding by yielding nearly identical rates for peptide release from E. coli ribosomes programmed with pseudouridylated and canonical stop codons. The crystal structure also brings insight into E. coli RF1-specific interactions and suggests involvement of L27 in bacterial translation termination. Our results are consistent with a mechanism in which read through of a pseudouridylated stop codon in bacteria results from increased decoding by near-cognate tRNAs (miscoding) rather than from decreased efficiency of termination. PMID:27107638

  19. Premature termination codons in modern human genomes

    PubMed Central

    Fujikura, Kohei

    2016-01-01

    The considerable range of genetic variation in human populations may partly reflect distinctive processes of adaptation to variable environmental conditions. However, the adaptive genomic signatures remain to be completely elucidated. This research explores candidate loci under selection at the population level by characterizing recently arisen premature termination codons (PTCs), some of which indicate a human knockout. From a total of 7595 participants from two population exome projects, 246 PTCs were found where natural selection has resulted in new alleles with a high frequency (from 1% to 96%) of derived alleles and various levels of population differentiation (FST = 0.00139–0.626). The PTC genes formed protein and regulatory networks limited to 15 biological processes or gene families, of which seven categories were previously unreported. PTC mutations have a strong tendency to be introduced into members of the same gene family, even during modern human evolution, although the exact nature of the selection is not fully known. The findings here suggest the ongoing evolutionary plasticity of modern humans at the genetic level and also partly provide insights into common human knockouts. PMID:26932450

  20. Premature termination codons in modern human genomes.

    PubMed

    Fujikura, Kohei

    2016-01-01

    The considerable range of genetic variation in human populations may partly reflect distinctive processes of adaptation to variable environmental conditions. However, the adaptive genomic signatures remain to be completely elucidated. This research explores candidate loci under selection at the population level by characterizing recently arisen premature termination codons (PTCs), some of which indicate a human knockout. From a total of 7595 participants from two population exome projects, 246 PTCs were found where natural selection has resulted in new alleles with a high frequency (from 1% to 96%) of derived alleles and various levels of population differentiation (FST = 0.00139-0.626). The PTC genes formed protein and regulatory networks limited to 15 biological processes or gene families, of which seven categories were previously unreported. PTC mutations have a strong tendency to be introduced into members of the same gene family, even during modern human evolution, although the exact nature of the selection is not fully known. The findings here suggest the ongoing evolutionary plasticity of modern humans at the genetic level and also partly provide insights into common human knockouts. PMID:26932450

  1. K-ras mutation at codon 12 in stage I pancreatic adenocarcinoma: analysis by laser capture microdissection and direct sequencing.

    PubMed

    Chang, M C; Chang, Y T; Wu, M S; Shun, C T; Tien, Y W; Lin, J T

    2001-05-01

    Pancreatic ductal adenocarcinoma has been reported to carry a rate mutation high in codon 12 of the K-ras oncogene. To avoid the pitfalls of conventional methods of tissue dissection that might affect the sensitivity and specificity of detecting K-ras mutation, laser capture microdissection (LCM) technique was used. Pancreatic adenocarcinoma tissues were obtained from 15 patients who underwent Whipple's procedure. Selected tissues procured by LCM were analyzed by direct sequencing after polymerase chain reaction amplification of K-ras sequences at codon 12. K-ras mutation was noted in nine patients. All mutations showed G to A substitution at codon 12. The mutational pattern (GGT to GAT) is similar in both western and eastern reports. LCM is a feasible method to effectively obtain pure tumor cells from a surgical specimen. It remains to be determined whether this low mutation rate is a result of relatively early stage of disease or different carcinogenesis in different geographic regions. PMID:11432318

  2. Genetic Code Expansion by Degeneracy Reprogramming of Arginyl Codons.

    PubMed

    Lee, Ki Baek; Hou, Chen Yuan; Kim, Chae-Eun; Kim, Dong-Myung; Suga, Hiroaki; Kang, Taek Jin

    2016-07-01

    The genetic code in most organisms codes for 20 proteinogenic amino acids or translation stop. In order to encode more than 20 amino acids in the coding system, one of stop codons is usually reprogrammed to encode a non-proteinogenic amino acid. Although this approach works, usually only one amino acid is added to the amino acid repertoire. In this study, we incorporated non-proteinogenic amino acids into a protein by using a sense codon. As all the codons are allocated in the universal genetic code, we destroyed all the tRNA(Arg) in a cell-free protein synthesis system by using a tRNA(Arg) -specific tRNase, colicin D. Then by supplementing the system with tRNACCU , the translation system was partially restored. Through this creative destruction, reprogrammable codons were successfully created in the system to encode modified lysines along with the 20 proteinogenic amino acids. PMID:27151886

  3. 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

  4. [Codon optimization and eukaryotic expression analysis of the analgesic peptide gene BmK AngM1 from Buthus martensii Karsch].

    PubMed

    Yang, Jin-ling; Gao, Li-li; Zhu, Ping; Hou, Qi; Wang, Fen; Yu, Wen-bo; Nie, Tao

    2012-10-01

    Codon bias is an important factor which influences heterologous gene expression. Optimizing codon sequence could improve expression level of heterologous gene. In order to improve the expression level of BmK AngM1 gene encoding the analgesic peptide from Buthus martensii Karsch in Pichia pastoris, the codon-optimized BmK AngM1 gene according to its cDNA sequence and the preference codon usage of P. pastoris were cloned into expression vector pPIC9K and then transformed into P. pastoris. The expersion of recombinant BmK AngM1 (rBmK AngM1) was inducced by methanol in the medium, and the expression level of the optimized BmK AngM1 gene was 3.7 times of the native one. These results suggested that the expression of BmK AngM1 in P. pastoris could be successfully improved by codon optimization. PMID:23289154

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

    PubMed Central

    2013-01-01

    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. PMID:23578255

  6. Codon optimization and expression of irisin in Pichia pastoris GS115.

    PubMed

    Duan, Huikun; Wang, Haisong; Ma, Baicheng; Jiang, Pingzhe; Tu, Peipei; Ni, Zaizhong; Li, Xiaodan; Li, Miao; Ma, Xiaofeng; Wang, Bin; Wu, Ri; Li, Minggang

    2015-08-01

    Irisin is a novel hormone which is related to many metabolic diseases. In order to illuminate the function and therapeutic effect of irisin, gaining active irisin is necessary. In this work, a codon-optimized irisin gene was designed according to Pichia pastoris synonymous codon usage bias and cloned into the pPIC9K expression vector. Sequencing result indicating that the sequence of irisin was consistent with the modified irisin and the irisin was in frame with α-factor secretion signal ATG. The plasmid pPIC9K-irisin was transformed into GS115 P. pastoris cells through electroporation. The positive transformants were screened on MD medium and analyzed by PCR. Five recombinant GS115/pPIC9K-irisin strains were obtained, but only one strain expressed irisin successfully. SDS-PAGE and Western blot were used to assess the expression level and purity of irisin. The irisin was also simply purified and the effect of pH value, methanol concentration and induction time on the production of irisin was investigated. The results showed that the best conditions of irisin expression were as follows: pH 6.0, 2.0% methanol and induction for 96 h. This work laid the basis for further investigation into the therapeutic and pharmacological effects of irisin, as well as development of irisin-based therapy. PMID:25931394

  7. 1What do first-time mothers worry about? A study of usage patterns and content of calls made to a postpartum support telephone hotline

    PubMed Central

    2010-01-01

    Background Telephone hotlines designed to address common concerns in the early postpartum could be a useful resource for parents. Our aim was to test the feasibility of using a telephone as an intervention in a randomized controlled trial. We also aimed to test to use of algorithms to address parental concerns through a telephone hotline. Methods Healthy first-time mothers were recruited from postpartum wards of hospitals throughout Lebanon. Participants were given the number of a 24-hour telephone hotline that they could access for the first four months after delivery. Calls were answered by a midwife using algorithms developed by the study team whenever possible. Callers with medical complaints were referred to their physicians. Call patterns and content were recorded and analyzed. Results Eighty-four of the 353 women enrolled (24%) used the hotline. Sixty percent of the women who used the service called more than once, and all callers reported they were satisfied with the service. The midwife received an average of three calls per day and most calls occurred during the first four weeks postpartum. Our algorithms were used to answer questions in 62.8% of calls and 18.6% of calls required referral to a physician. Of the questions related to mothers, 66% were about breastfeeding. Sixty percent of questions related to the infant were about routine care and 23% were about excessive crying. Conclusions Utilization of a telephone hotline service for postpartum support is highest in the first four weeks postpartum. Most questions are related to breastfeeding, routine newborn care, and management of a fussy infant. It is feasible to test a telephone hotline as an intervention in a randomized controlled trial. Algorithms can be developed to provide standardized answers to the most common questions. PMID:20946690

  8. The Effect of Codon Mismatch on the Protein Translation System

    PubMed Central

    Cao, Liaoran; Li, Guohui; Cheng, Hong

    2016-01-01

    Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5’ ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer. PMID:26840415

  9. Cloning and expression of a codon-optimized gene encoding the influenza A virus nucleocapsid protein in Lactobacillus casei.

    PubMed

    Suebwongsa, Namfon; Panya, Marutpong; Namwat, Wises; Sookprasert, Saovaluk; Redruello, Begoña; Mayo, Baltasar; Alvarez, Miguel A; Lulitanond, Viraphong

    2013-06-01

    Lactic acid bacteria (LAB) species are envisioned as promising vehicles for the mucosal delivery of therapeutic and prophylactic molecules, including the development of oral vaccines. In this study, we report on the expression of a synthetic nucleocapsid (NP) gene of influenza A virus in Lactobacillus casei. The NP gene was re-designed based on the tRNA pool and the codon usage preference of L. casei BL23. The codon-optimized NP gene was then cloned and expressed in L. casei RCEID02 under the control of a constitutive promoter, that of the lactate dehydrogenase (ldh) gene. The synthetic NP gene was further expressed in L. casei EM116 under the control of an inducible promoter, that of the structural gene of nisin (nisA) from Lactococcus lactis. Based on Western blot analysis, the specific protein band of NP, with a molecular mass of 56.0 kDa, was clearly detected in both expression systems. Thus, our study demonstrates the success of expressing a codon-optimized influenza A viral gene in L. casei. The suitability of the recombinant LAB strains for immunization purposes is currently under evaluation. PMID:24400527

  10. CMSU Library Usage: Telephone Survey Results.

    ERIC Educational Resources Information Center

    Wales, Barbara; And Others

    The Assessment Committee of Library Services at Central Missouri State University conducted a telephone survey of 500 (41.2% completion rate) university students. The goals were to use a random sampling in order to gain more information regarding usage patterns of library services; to identify factors which inhibit patron use; and to reveal…