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Sample records for codon adaptation indices

  1. An environmental signature for 323 microbial genomes based on codon adaptation indices

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Friis, Carsten; Juncker, Agnieszka

    2006-01-01

    Background: Codon adaptation indices ( CAIs) represent an evolutionary strategy to modulate gene expression and have widely been used to predict potentially highly expressed genes within microbial genomes. Here, we evaluate and compare two very different methods for estimating CAI values, one......: The results and the approach described here may be used to acquire new knowledge regarding species lifestyle and to elucidate relationships between organisms that are far apart evolutionarily....

  2. Analysis of Synonymous Codon Usage Bias of Zika Virus and Its Adaption to the Hosts.

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    Wang, Hongju; Liu, Siqing; Zhang, Bo; Wei, Wenqiang

    2016-01-01

    Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash, fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias analysis can reveal much about the molecular evolution and host adaption of ZIKV. To gain insight into the evolutionary characteristics of ZIKV, we performed a comprehensive analysis on the codon usage pattern in 46 ZIKV strains by calculating the effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and other indicators. The results indicate that the codon usage bias of ZIKV is relatively low. Several lines of evidence support the hypothesis that translational selection plays a role in shaping the codon usage pattern of ZIKV. The results from a correspondence analysis (CA) indicate that other factors, such as base composition, aromaticity, and hydrophobicity may also be involved in shaping the codon usage pattern of ZIKV. Additionally, the results from a comparative analysis of RSCU between ZIKV and its hosts suggest that ZIKV tends to evolve codon usage patterns that are comparable to those of its hosts. Moreover, selection pressure from Homo sapiens on the ZIKV RSCU patterns was found to be dominant compared with that from Aedes aegypti and Aedes albopictus. Taken together, both natural translational selection and mutation pressure are important for shaping the codon usage pattern of ZIKV. Our findings contribute to understanding the evolution of ZIKV and its adaption to its hosts.

  3. Analysis of codon usage bias of Crimean-Congo hemorrhagic fever virus and its adaptation to hosts.

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    Rahman, Siddiq Ur; Yao, Xiaoting; Li, Xiangchen; Chen, Dekun; Tao, Shiheng

    2018-03-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a negative-sense, single stranded RNA virus with a three-segmented genome that belongs to the genus Nairovirus within the family Bunyaviridae. CCHFV uses Hyalomma ticks as a vector to infect humans with a wide range of clinical signs, from asymptomatic to Zika-like syndrome. Despite significant progress in genomic analyses, the influences of viral relationships with different hosts on overall viral fitness, survival, and evading the host's immune systems remain unknown. To better understand the evolutionary characteristics of CCHFV, we performed a comprehensive analysis of the codon usage pattern in 179 CCHFV strains by calculating the relative synonymous codon usage (RSCU), effective number of codons (ENC), codon adaptation index (CAI), and other indicators. The results indicate that the codon usage bias of CCHFV is relatively low. Several lines of evidence support the hypothesis that a translation selection factor is shaping codon usage pattern in this virus. A correspondence analysis (CA) showed that other factors, such as base composition, aromaticity, and hydrophobicity may also be involved in shaping the codon usage pattern of CCHFV. Additionally, the results from a comparative analysis of RSCU between CCHFV and its hosts suggest that CCHFV tends to evolve codon usage patterns that are comparable to those of its hosts. Furthermore, the selection pressures from Homo sapiens, Bos taurus, and Ovis aries on the CCHFV RSCU patterns were dominant when compared with selection pressure from Hyalomma spp. vectors. Taken together, both natural selection and mutation pressure are important for shaping the codon usage pattern of CCHFV. We believe that such findings will assist researchers in understanding the evolution of CCHFV and its adaptation to its hosts. Copyright © 2017. Published by Elsevier B.V.

  4. Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development

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    Goñi Natalia

    2012-11-01

    Full Text Available Abstract Background Influenza A virus (IAV is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed. Results We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA on relative synonymous codon usage (RSCU is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process. Conclusions A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines.

  5. Adaptation of Borrelia burgdorferi to its natural hosts by synonymous codon and amino acid usage.

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    Ma, Xiao-Xia; Ma, Peng; Chang, Qiu-Yan; Liu, Zhen-Bin; Zhang, Derong; Zhou, Xiao-Kai; Ma, Zhong-Ren; Cao, Xin

    2018-03-13

    Lyme disease, caused by Borrelia burgdorferi, is a focally endemic tick-transmitted zoonotic infection. In this study, the major factors underlying synonymous codon-related amino acid usage in the B. burgdorferi genome and bias in synonymous codon usage of the translation initiation region of coding sequences were analyzed. Additionally, adaptation of B. burgdorferi to several of its hosts was analyzed in the context of synonymous codon usage. Principal component analysis (PCA) revealed that nucleotide content at the third synonymous position of a codon influenced the synonymous codon usage pattern, but the strand-specific factor did not influence the synonymous codon usage pattern of B. burgdorferi. In terms of the low GC content of B. burgdorferi coding sequences, the effective number of codons (ENC) showed a significant correlation with GC 3 content (at the synonymous position). For the amino acid usage pattern for B. burgdorferi, PCA showed that the strand-specific factor did not contribute to this pattern, while the properties (aromaticity and hydrophobicity) of the amino acids themselves showed strong correlations with this pattern. Under-represented codons, which were frequently selected in the translation initiation region, possibly play roles in regulating gene expression in B. burgdorferi. In terms of co-evolution and synonymous codon usage patterns, adaptation of B. burgdorferi to different intermediate hosts was apparent to different degrees, and the degree of adaptation of this spirochete to wild animals was stronger than that of humans or mice. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Does adaptation to vertebrate codon usage relate to flavivirus emergence potential?

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    Di Paola, Nicholas; Freire, Caio César de Melo; Zanotto, Paolo Marinho de Andrade

    2018-01-01

    Codon adaptation index (CAI) is a measure of synonymous codon usage biases given a usage reference. Through mutation, selection, and drift, viruses can optimize their replication efficiency and produce more offspring, which could increase the chance of secondary transmission. To evaluate how higher CAI towards the host has been associated with higher viral titers, we explored temporal trends of several historic and extensively sequenced zoonotic flaviviruses and relationships within the genus itself. To showcase evolutionary and epidemiological relationships associated with silent, adaptive synonymous changes of viruses, we used codon usage tables from human housekeeping and antiviral immune genes, as well as tables from arthropod vectors and vertebrate species involved in the flavivirus maintenance cycle. We argue that temporal trends of CAI changes could lead to a better understanding of zoonotic emergences, evolutionary dynamics, and host adaptation. CAI appears to help illustrate historically relevant trends of well-characterized viruses, in different viral species and genetic diversity within a single species. CAI can be a useful tool together with in vivo and in vitro kinetics, phylodynamics, and additional functional genomics studies to better understand species trafficking and viral emergence in a new host.

  7. Adaptation to different human populations by HIV-1 revealed by codon-based analyses.

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    Sergei L Kosakovsky Pond

    2006-06-01

    Full Text Available Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that persist in a population and another for detecting whether selection is operating differentially on individual codons of a gene sampled from two different populations. Applying these methods to two HIV populations infecting genetically distinct human hosts, we have found that few of the positively selected amino acid sites persist in the population; the other changes are detected only at the tips of the phylogenetic tree and appear deleterious in the long term. Additionally, we have identified seven amino acid sites in protease and reverse transcriptase that are selected differentially in the two samples, demonstrating specific population-level adaptation of HIV to human populations.

  8. Analysing codon usage bias of cyprinid herpesvirus 3 and adaptation of this virus to the hosts.

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    Ma, Y P; Liu, Z X; Hao, L; Ma, J Y; Liang, Z L; Li, Y G; Ke, H

    2015-07-01

    The codon usage patterns of open reading frames (ORFs) in cyprinid herpesvirus 3 (CyHV-3) have been investigated in this study. The high correlation between GC12 % and GC3 % suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage and base component in the CyHV-3, while mutational pressure effect results from the high correlation between GC3 % and the first principal axis of principle component analysis (Axis 1) on the relative synonymous codon usage (RSCU) value of the viral functional genes. However, 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 mutational pressure. It is noted that the similarity degree of codon usage between the CyHV-3 and goldfish, Carassius auratus (L.), is higher than that between the virus and common carp, Cyprinus carpio L., suggesting that the goldfish plays a more important role than the common carp in codon usage pattern of the CyHV-3. The study of codon usage in CyHV-3 can provide some evidence about the molecular evolution of the virus. It can also enrich our understanding about the relationship between the CyHV-3 and its hosts by analysing their codon usage patterns. © 2014 John Wiley & Sons Ltd.

  9. Analysis of synonymous codon usage patterns in the genus Rhizobium.

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

    2013-11-01

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

  10. Evolution of Synonymous Codon Usage Bias in West African and Central African Strains of Monkeypox Virus.

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    Karumathil, Sudeesh; Raveendran, Nimal T; Ganesh, Doss; Kumar Ns, Sampath; Nair, Rahul R; Dirisala, Vijaya R

    2018-01-01

    The evolution of bias in synonymous codon usage in chosen monkeypox viral genomes and the factors influencing its diversification have not been reported so far. In this study, various trends associated with synonymous codon usage in chosen monkeypox viral genomes were investigated, and the results are reported. Identification of factors that influence codon usage in chosen monkeypox viral genomes was done using various codon usage indices, such as the relative synonymous codon usage, the effective number of codons, and the codon adaptation index. The Spearman rank correlation analysis and a correspondence analysis were used for correlating various factors with codon usage. The results revealed that mutational pressure due to compositional constraints, gene expression level, and selection at the codon level for utilization of putative optimal codons are major factors influencing synonymous codon usage bias in monkeypox viral genomes. A cluster analysis of relative synonymous codon usage values revealed a grouping of more virulent strains as one major cluster (Central African strains) and a grouping of less virulent strains (West African strains) as another major cluster, indicating a relationship between virulence and synonymous codon usage bias. This study concluded that a balance between the mutational pressure acting at the base composition level and the selection pressure acting at the amino acid level frames synonymous codon usage bias in the chosen monkeypox viruses. The natural selection from the host does not seem to have influenced the synonymous codon usage bias in the analyzed monkeypox viral genomes.

  11. Codon usage and codon pair patterns in non-grass monocot genomes.

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    Mazumdar, Purabi; Binti Othman, RofinaYasmin; Mebus, Katharina; Ramakrishnan, N; Ann Harikrishna, Jennifer

    2017-11-28

    Studies on codon usage in monocots have focused on grasses, and observed patterns of this taxon were generalized to all monocot species. Here, non-grass monocot species were analysed to investigate the differences between grass and non-grass monocots. First, studies of codon usage in monocots were reviewed. The current information was then extended regarding codon usage, as well as codon-pair context bias, using four completely sequenced non-grass monocot genomes (Musa acuminata, Musa balbisiana, Phoenix dactylifera and Spirodela polyrhiza) for which comparable transcriptome datasets are available. Measurements were taken regarding relative synonymous codon usage, effective number of codons, derived optimal codon and GC content and then the relationships investigated to infer the underlying evolutionary forces. The research identified optimal codons, rare codons and preferred codon-pair context in the non-grass monocot species studied. In contrast to the bimodal distribution of GC3 (GC content in third codon position) in grasses, non-grass monocots showed a unimodal distribution. Disproportionate use of G and C (and of A and T) in two- and four-codon amino acids detected in the analysis rules out the mutational bias hypothesis as an explanation of genomic variation in GC content. There was found to be a positive relationship between CAI (codon adaptation index; predicts the level of expression of a gene) and GC3. In addition, a strong correlation was observed between coding and genomic GC content and negative correlation of GC3 with gene length, indicating a strong impact of GC-biased gene conversion (gBGC) in shaping codon usage and nucleotide composition in non-grass monocots. Optimal codons in these non-grass monocots show a preference for G/C in the third codon position. These results support the concept that codon usage and nucleotide composition in non-grass monocots are mainly driven by gBGC. © The Authors 2017. Published by Oxford University Press on

  12. Canine parvovirus type 2 (CPV-2) and Feline panleukopenia virus (FPV) codon bias analysis reveals a progressive adaptation to the new niche after the host jump.

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    Franzo, Giovanni; Tucciarone, Claudia Maria; Cecchinato, Mattia; Drigo, Michele

    2017-09-01

    Based on virus dependence from host cell machinery, their codon usage is expected to show a strong relation with the host one. Even if this association has been stated, especially for bacteria viruses, the linkage is considered to be less consistent for more complex organisms and a codon bias adaptation after host jump has never been proven. Canine parvovirus type 2 (CPV-2) was selected as a model because it represents a well characterized case of host jump, originating from Feline panleukopenia virus (FPV). The current study demonstrates that the adaptation to specific tissue and host codon bias affected CPV-2 evolution. Remarkably, FPV and CPV-2 showed a higher closeness toward the codon bias of the tissues they display the higher tropism for. Moreover, after the host jump, a clear and significant trend was evidenced toward a reduction in the distance between CPV-2 and the dog codon bias over time. This evidence was not confirmed for FPV, suggesting that an equilibrium has been reached during the prolonged virus-host co-evolution. Additionally, the presence of an intermediate pattern displayed by some strains infecting wild species suggests that these could have facilitated the host switch also by acting on codon bias. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Genome-wide analysis of codon usage and influencing factors in chikungunya viruses.

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    Azeem Mehmood Butt

    Full Text Available 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.

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

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    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

  15. Codon Bias Patterns of E. coli's Interacting Proteins.

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    Maddalena Dilucca

    Full Text Available 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.

  16. Efficient expression of codon-adapted affinity tagged super folder green fluorescent protein for synchronous protein localization and affinity purification studies in Tetrahymena thermophila.

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    Yilmaz, Gürkan; Arslanyolu, Muhittin

    2015-03-25

    A superior Green Fluorescent Protein (GFP) mutant, known as superfolder GFP (sfGFP), is more soluble, faster folding, and is the brightest of the known GFP mutants. This study aimed to create a codon-adapted sfGFP tag (TtsfGFP) for simultaneous protein localization and affinity purification in Tetrahymena thermophila. In vivo fluorescence spectroscopic analyses of clones carrying a codon-adapted and 6 × His tagged TtsfGFP cassette showed approximately 2-4-fold increased fluorescence emission compared with the control groups at 3 h. Fluorescence microscopy also revealed that TtsfGFP reached its emission maxima at 100 min, which was much earlier than controls expressing EGFP and sfGFP (240 min). A T. thermophila ATP-dependent DNA ligase domain containing hypothetical gene (H) was cloned into the 3' end of 6 × His-TtsfGFP to assess the affinity/localization dual tag feature. Fluorescence microscopy of the 6 × His-TtsfGFP-H clone confirmed its localization in the macro- and micronucleus of vegetative T. thermophila. Simultaneous affinity purification of TtsfGFP and TtsfGFP-H with Ni-NTA beads was feasible, as shown by Ni-NTA purified proteins analysis by SDS-PAGE and western blotting. We successfully codon adapted the N-terminal 6 × His-TtsfGFP tag and showed that it could be used for protein localization and affinity purification simultaneously in T. thermophila. We believe that this dual tag will advance T. thermophila studies by providing strong visual traceability of the target protein in vivo and in vitro during recombinant production of heterologous and homologous proteins.

  17. Codon optimization underpins generalist parasitism in fungi.

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    Badet, Thomas; Peyraud, Remi; Mbengue, Malick; Navaud, Olivier; Derbyshire, Mark; Oliver, Richard P; Barbacci, Adelin; Raffaele, Sylvain

    2017-02-03

    The range of hosts that parasites can infect is a key determinant of the emergence and spread of disease. Yet, the impact of host range variation on the evolution of parasite genomes remains unknown. Here, we show that codon optimization underlies genome adaptation in broad host range parasites. We found that the longer proteins encoded by broad host range fungi likely increase natural selection on codon optimization in these species. Accordingly, codon optimization correlates with host range across the fungal kingdom. At the species level, biased patterns of synonymous substitutions underpin increased codon optimization in a generalist but not a specialist fungal pathogen. Virulence genes were consistently enriched in highly codon-optimized genes of generalist but not specialist species. We conclude that codon optimization is related to the capacity of parasites to colonize multiple hosts. Our results link genome evolution and translational regulation to the long-term persistence of generalist parasitism.

  18. Quantifying Position-Dependent Codon Usage Bias

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    Hockenberry, Adam J.; Sirer, M. Irmak; Amaral, Luís A. Nunes; Jewett, Michael C.

    2014-01-01

    Although the mapping of codon to amino acid is conserved across nearly all species, the frequency at which synonymous codons are used varies both between organisms and between genes from the same organism. This variation affects diverse cellular processes including protein expression, regulation, and folding. Here, we mathematically model an additional layer of complexity and show that individual codon usage biases follow a position-dependent exponential decay model with unique parameter fits for each codon. We use this methodology to perform an in-depth analysis on codon usage bias in the model organism Escherichia coli. Our methodology shows that lowly and highly expressed genes are more similar in their codon usage patterns in the 5′-gene regions, but that these preferences diverge at distal sites resulting in greater positional dependency (pD, which we mathematically define later) for highly expressed genes. We show that position-dependent codon usage bias is partially explained by the structural requirements of mRNAs that results in increased usage of A/T rich codons shortly after the gene start. However, we also show that the pD of 4- and 6-fold degenerate codons is partially related to the gene copy number of cognate-tRNAs supporting existing hypotheses that posit benefits to a region of slow translation in the beginning of coding sequences. Lastly, we demonstrate that viewing codon usage bias through a position-dependent framework has practical utility by improving accuracy of gene expression prediction when incorporating positional dependencies into the Codon Adaptation Index model. PMID:24710515

  19. Evolution of codon usage in Zika virus genomes is host and vector specific

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    Butt, Azeem Mehmood; Nasrullah, Izza; Qamar, Raheel; Tong, Yigang

    2016-01-01

    The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors. PMID:27729643

  20. Codon usage pattern in human SPANX genes.

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    Choudhury, Monisha Nath; Chakraborty, Supriyo

    2015-01-01

    SPANX (sperm protein coupled with the nucleus in the X chromosome) genes play a crucial role in human spermatogenesis. Codon usage bias (CUB) is a well-known phenomenon that exists in many genomes and mainly determined by mutation and selection. CUB is species specific and a unique characteristic of a genome. Analysis of compositional features and codon usage pattern of SPANX genes in human has contributed to explore the molecular biology of this gene. In our current study, we have retrieved the sequences of different variants of SPANX gene from NCBI using accession number and a perl script was used to analyze the nucleotide composition and the parameters for codon usage bias. Our results showed that codon usage bias is low as measured by codon bias index (CBI) and most of the GC ending codons were positively correlated with GC bias as indicated by GC3. That mutation pressure and natural selection affect the codon usage pattern were revealed by correspondence analysis (COA) and neutrality plot. Moreover, the neutrality plot further suggested that the role of natural selection is higher than mutation pressure on SPANX genes. The codon usage bias in SPANX genes is not very high and the role of natural selection dominates over mutation pressure in the codon usage of human SPANX genes.

  1. Codon usage of HIV regulatory genes is not determined by nucleotide composition.

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    Phakaratsakul, Supinya; Sirihongthong, Thanyaporn; Boonarkart, Chompunuch; Suptawiwat, Ornpreya; Auewarakul, Prasert

    2018-02-01

    Codon usage bias can be a result of either mutational bias or selection for translational efficiency and/or accuracy. Previous data has suggested that nucleotide composition constraint was the main determinant of HIV codon usage, and that nucleotide composition and codon usage were different between the regulatory genes, tat and rev, and other viral genes. It is not clear whether translational selection contributed to the codon usage difference and how nucleotide composition and translational selection interact to determine HIV codon usage. In this study, a model of codon bias due to GC composition with modification for the A-rich third codon position was used to calculate predicted HIV codon frequencies based on its nucleotide composition. The predicted codon usage of each gene was compared with the actual codon frequency. The predicted codon usage based on GC composition matched well with the actual codon frequencies for the structural genes (gag, pol and env). However, the codon usage of the regulatory genes (tat and rev) could not be predicted. Codon usage of the regulatory genes was also relatively unbiased showing the highest effective number of codons (ENC). Moreover, the codon adaptation index (CAI) of the regulatory genes showed better adaptation to human codons when compared to other HIV genes. Therefore, the early expressed genes responsible for regulation of the replication cycle, tat and rev, were more similar to humans in terms of codon usage and GC content than other HIV genes. This may help these genes to be expressed efficiently during the early stages of infection.

  2. Nucleotide composition and codon usage bias of SRY gene.

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    Choudhury, M N; Uddin, A; Chakraborty, S

    2018-02-01

    The SRY gene is present within the sex-determining region of the Y chromosome which is responsible for maleness in mammals. The nonuniform usage of synonymous codons in the mRNA transcript for encoding a particular amino acid is the codon usage bias (CUB). Analysis of codon usage pattern is important to understand the genetic and molecular organisation of a gene. It also helps in heterologous gene expression, design of primer and synthetic gene. However, the analysis of codon usage bias of SRY gene was not yet studied. We have used bioinformatic tools to analyse codon usage bias of SRY gene across mammals. Codon bias index (CBI) indicated that the overall extent of codon usage bias was weak. The relative synonymous codon usage (RSCU) analysis suggested that most frequently used codons had an A or C at the third codon position. Compositional constraint played an important role in codon usage pattern as evident from correspondence analysis (CA). Significant correlation among nucleotides constraints indicated that both mutation pressure and natural selection affect the codon usage pattern. Neutrality plot suggested that natural selection might play a major role, while mutation pressure might play a minor role in codon usage pattern in SRY gene in different species of mammals. © 2017 Blackwell Verlag GmbH.

  3. Temperature adaptation of synonymous codon usage in different functional categories of genes: a comparative study between homologous genes of Methanococcus jannaschii and Methanococcus maripaludis.

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    Basak, Surajit; Ghosh, Tapash Chandra

    2006-07-10

    Synonymous codon usage of homologous sequences between Methanococcus jannaschii and Methanococcus maripaludis have been analyzed in three broad functional categories of genes namely: (i) information storage and processing; (ii) metabolism; and (iii) cellular processes and signaling. Average values of synonymous nucleotide substitutions per synonymous site are significantly lower for information processing genes compared to either metabolic or cellular processing genes. These results suggests that synonymous codon usage has been subject to greater constraint in the information storage and processing group of genes compared to other functional categories of genes. For metabolic and cellular processing genes, correspondence analysis based on relative synonymous codon usage (RSCU) values separates the genes along the first major axes according to the genome type; while in the information processing group, genes are separated along the second major axes according to the genome type. Further study on synonymous substitution rate for information processing genes shows a stronger selective constraint on synonymous codon usage of six amino acids, G,A,R,P,Y,F. Randomization of the original transcript of M. jannaschii for information processing genes suggests that variation in selective constraint between synonymous codon usage is related to the potential formation of mRNA secondary structures which contribute to the folding stability.

  4. Genomic composition factors affect codon usage in porcine genome

    DEFF Research Database (Denmark)

    Khobondo, J O; Okeno, Tobias O; Kahi, A K

    2015-01-01

    The objective of the study was to determine the codon usage bias in the porcine genome and decipher its determinants. To investigate the underlying mechanisms of codon bias, the coding sequence (CDS) from the swine reference sequence (ssc10.2) was extracted using Biomart. An in house built Perl...... script was used to derive various genomic traits and codon indices. Analysis was done using R statistical package, and correlations and multivariate regressions were performed. We report the existence of codon usage bias that might suggest existence of weak translational selection. The codon bias...

  5. Sobol indices for dimension adaptivity in sparse grids

    NARCIS (Netherlands)

    Dwight, R.P.; Desmedt, S.G.L.; Shoeibi Omrani, P.

    2016-01-01

    Propagation of random variables through computer codes of many inputs is primarily limited by computational expense. The use of sparse grids mitigates these costs somewhat; here we show how Sobol indices can be used to perform dimension adaptivity to mitigate them further. The method is compared to

  6. Coupling between protein level selection and codon usage optimization in the evolution of bacteria and archaea.

    Science.gov (United States)

    Ran, Wenqi; Kristensen, David M; Koonin, Eugene V

    2014-03-25

    The relationship between the selection affecting codon usage and selection on protein sequences of orthologous genes in diverse groups of bacteria and archaea was examined by using the Alignable Tight Genome Clusters database of prokaryote genomes. The codon usage bias is generally low, with 57.5% of the gene-specific optimal codon frequencies (Fopt) being below 0.55. This apparent weak selection on codon usage contrasts with the strong purifying selection on amino acid sequences, with 65.8% of the gene-specific dN/dS ratios being below 0.1. For most of the genomes compared, a limited but statistically significant negative correlation between Fopt and dN/dS was observed, which is indicative of a link between selection on protein sequence and selection on codon usage. The strength of the coupling between the protein level selection and codon usage bias showed a strong positive correlation with the genomic GC content. Combined with previous observations on the selection for GC-rich codons in bacteria and archaea with GC-rich genomes, these findings suggest that selection for translational fine-tuning could be an important factor in microbial evolution that drives the evolution of genome GC content away from mutational equilibrium. This type of selection is particularly pronounced in slowly evolving, "high-status" genes. A significantly stronger link between the two aspects of selection is observed in free-living bacteria than in parasitic bacteria and in genes encoding metabolic enzymes and transporters than in informational genes. These differences might reflect the special importance of translational fine-tuning for the adaptability of gene expression to environmental changes. The results of this work establish the coupling between protein level selection and selection for translational optimization as a distinct and potentially important factor in microbial evolution. IMPORTANCE Selection affects the evolution of microbial genomes at many levels, including both

  7. Molecular evolution of synonymous codon usage in Populus

    Directory of Open Access Journals (Sweden)

    Ingvarsson Pär K

    2008-11-01

    Full Text Available Abstract Background Evolution of synonymous codon usage is thought to be determined by a balance between mutation, genetic drift and natural selection on translational efficiency. However, natural selection on codon usage is considered to be a weak evolutionary force and selection on codon usage is expected to be strongest in species with large effective population sizes. Results I examined the evolution of synonymous codons using EST data from five species of Populus. Data on relative synonymous codon usage in genes with high and low gene expression were used to identify 25 codons from 18 different amino acids that were deemed to be preferred codons across all five species. All five species show significant correlations between codon bias and gene expression, independent of base composition, thus indicating that translational selection has shaped synonymous codon usage. Using a set of 158 orthologous genes I detected an excess of unpreferred to preferred (U → P mutations in two lineages, P. tremula and P. deltoides. Maximum likelihood estimates of the strength of selection acting on synonymous codons was also significantly greater than zero in P. tremula, with the ML estimate of 4Nes = 0.720. Conclusion The data is consistent with weak selection on preferred codons in all five species. There is also evidence suggesting that selection on synonymous codons has increased in P. tremula. Although the reasons for the increase in selection on codon usage in the P. tremula lineage are not clear, one possible explanation is an increase in the effective population size in P. tremula.

  8. DNATagger, colors for codons.

    Science.gov (United States)

    Scherer, N M; Basso, D M

    2008-09-16

    DNATagger is a web-based tool for coloring and editing DNA, RNA and protein sequences and alignments. It is dedicated to the visualization of protein coding sequences and also protein sequence alignments to facilitate the comprehension of evolutionary processes in sequence analysis. The distinctive feature of DNATagger is the use of codons as informative units for coloring DNA and RNA sequences. The codons are colored according to their corresponding amino acids. It is the first program that colors codons in DNA sequences without being affected by "out-of-frame" gaps of alignments. It can handle single gaps and gaps inside the triplets. The program also provides the possibility to edit the alignments and change color patterns and translation tables. DNATagger is a JavaScript application, following the W3C guidelines, designed to work on standards-compliant web browsers. It therefore requires no installation and is platform independent. The web-based DNATagger is available as free and open source software at http://www.inf.ufrgs.br/~dmbasso/dnatagger/.

  9. Comparative analysis of codon usage patterns and identification of predicted highly expressed genes in five Salmonella genomes

    Directory of Open Access Journals (Sweden)

    Mondal U

    2008-01-01

    Full Text Available Purpose: To anlyse codon usage patterns of five complete genomes of Salmonella , predict highly expressed genes, examine horizontally transferred pathogenicity-related genes to detect their presence in the strains, and scrutinize the nature of highly expressed genes to infer upon their lifestyle. Methods: Protein coding genes, ribosomal protein genes, and pathogenicity-related genes were analysed with Codon W and CAI (codon adaptation index Calculator. Results: Translational efficiency plays a role in codon usage variation in Salmonella genes. Low bias was noticed in most of the genes. GC3 (guanine cytosine at third position composition does not influence codon usage variation in the genes of these Salmonella strains. Among the cluster of orthologous groups (COGs, translation, ribosomal structure biogenesis [J], and energy production and conversion [C] contained the highest number of potentially highly expressed (PHX genes. Correspondence analysis reveals the conserved nature of the genes. Highly expressed genes were detected. Conclusions: Selection for translational efficiency is the major source of variation of codon usage in the genes of Salmonella . Evolution of pathogenicity-related genes as a unit suggests their ability to infect and exist as a pathogen. Presence of a lot of PHX genes in the information and storage-processing category of COGs indicated their lifestyle and revealed that they were not subjected to genome reduction.

  10. Codon usage pattern of complex III gene of respiratory chain among platyhelminths.

    Science.gov (United States)

    Mazumder, Gulshana A; Uddin, Arif; Chakraborty, Supriyo

    2018-01-01

    Codon usage bias refers to the phenomenon where synonymous codons are used with unequal frequencies. To understand the patterns of codon usage in mitochondrial cytochrome B (MT-CYB) gene of phylum platyhelminthes we used bioinformatic approaches to analyze the protein coding sequences of five different classes - cestoda, monogenea, rabditophora, trematoda and turbellaria. It was found from nucleotide composition analysis that in all the classes, A/T-ended codons were preferred to G/C -ended codons. From box plot analysis GC1 was found to have highest response to codon usage bias. Correspondence analysis indicated that besides mutation other factors such as natural selection might also affect the codon usage pattern. Neutrality plot reveals that both mutation and natural selection played role in codon usage pattern in five classes of MT-CYB gene. Various factors namely nucleotide composition, natural selection and mutation pressure affected the codon usage pattern. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. A new and updated resource for codon usage tables.

    Science.gov (United States)

    Athey, John; Alexaki, Aikaterini; Osipova, Ekaterina; Rostovtsev, Alexandre; Santana-Quintero, Luis V; Katneni, Upendra; Simonyan, Vahan; Kimchi-Sarfaty, Chava

    2017-09-02

    Due to the degeneracy of the genetic code, most amino acids can be encoded by multiple synonymous codons. Synonymous codons naturally occur with different frequencies in different organisms. The choice of codons may affect protein expression, structure, and function. Recombinant gene technologies commonly take advantage of the former effect by implementing a technique termed codon optimization, in which codons are replaced with synonymous ones in order to increase protein expression. This technique relies on the accurate knowledge of codon usage frequencies. Accurately quantifying codon usage bias for different organisms is useful not only for codon optimization, but also for evolutionary and translation studies: phylogenetic relations of organisms, and host-pathogen co-evolution relationships, may be explored through their codon usage similarities. Furthermore, codon usage has been shown to affect protein structure and function through interfering with translation kinetics, and cotranslational protein folding. Despite the obvious need for accurate codon usage tables, currently available resources are either limited in scope, encompassing only organisms from specific domains of life, or greatly outdated. Taking advantage of the exponential growth of GenBank and the creation of NCBI's RefSeq database, we have developed a new database, the High-performance Integrated Virtual Environment-Codon Usage Tables (HIVE-CUTs), to present and analyse codon usage tables for every organism with publicly available sequencing data. Compared to existing databases, this new database is more comprehensive, addresses concerns that limited the accuracy of earlier databases, and provides several new functionalities, such as the ability to view and compare codon usage between individual organisms and across taxonomical clades, through graphical representation or through commonly used indices. In addition, it is being routinely updated to keep up with the continuous flow of new data in

  12. Gene expression, nucleotide composition and codon usage bias of genes associated with human Y chromosome.

    Science.gov (United States)

    Choudhury, Monisha Nath; Uddin, Arif; Chakraborty, Supriyo

    2017-06-01

    Analysis of codon usage pattern is important to understand the genetic and evolutionary characteristics of genomes. We have used bioinformatic approaches to analyze the codon usage bias (CUB) of the genes located in human Y chromosome. Codon bias index (CBI) indicated that the overall extent of codon usage bias was low. The relative synonymous codon usage (RSCU) analysis suggested that approximately half of the codons out of 59 synonymous codons were most frequently used, and possessed a T or G at the third codon position. The codon usage pattern was different in different genes as revealed from correspondence analysis (COA). A significant correlation between effective number of codons (ENC) and various GC contents suggests that both mutation pressure and natural selection affect the codon usage pattern of genes located in human Y chromosome. In addition, Y-linked genes have significant difference in GC contents at the second and third codon positions, expression level, and codon usage pattern of some codons like the SPANX genes in X chromosome.

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

    Directory of Open Access Journals (Sweden)

    O'Connell Mary J

    2012-07-01

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

  14. Estimate Codon Usage Bias Using Codon Usage Analyzer (CUA).

    Science.gov (United States)

    Zhang, Zhenguo; Sablok, Gaurav

    2018-01-01

    One amino acid is added to a growing peptide by a ribosome through reading triple nucleotides, i.e., a codon, each time. Twenty species of amino acids are often coded by 61 codons, so one amino acid can be coded by more than one codon and the codons coding the same amino acid are called synonymous. Intriguingly, synonymous codons' usage is often uneven: some are used more often than their alternatives in a genome. The unevenness of codon usage is termed codon usage bias (CUB). CUB is widespread, and its causes and consequences have been under intensive investigation. To facilitate the studying of CUB, in this chapter we present a protocol of estimating CUB by using the free software Codon Usage Analyzer, and apply it to Brachypodium distachyon as an example. To accomplish this protocol, the readers need some basic command-line skills. Briefly, the protocol comprises four major steps: downloading data and software, setting up computing environment, preparing data, and estimating CUB.

  15. Comparison of growth and yield adaptability indicators of two maize ...

    African Journals Online (AJOL)

    . ) cultivars under planting basin technique in Zimbabwe. ... season maize cultivars (P2859W and PHB3253) should opt for PHB3253 for better productivity. Key words: Early maturing cultivars, PHB3253 and P2859W performance, adaptation.

  16. Urban heat indicator map for climate adaptation planning

    NARCIS (Netherlands)

    Groot-Reichwein, de M.A.M.; Lammeren, van R.J.A.; Goosen, H.; Koekoek, A.; Bregt, A.K.; Vellinga, P.

    2018-01-01

    By 2050, 75 % of the world’s population will live in cities and the occurrence of heat wave events might have doubled. Mapping the climate and land use change impact for urban heat events should set the agenda for adaptation planning at the local scale. Literature on urban heat mapping does not

  17. Comparison of growth and yield adaptability indicators of two maize ...

    African Journals Online (AJOL)

    admin

    2017-01-04

    Jan 4, 2017 ... It is therefore recommended that farmers who use planting basins in semi-arid areas for growing short season maize cultivars (P2859W and PHB3253) should opt for PHB3253 for better productivity. Key words: Early maturing cultivars, PHB3253 and P2859W performance, adaptation. INTRODUCTION.

  18. Synonymous codon usage of genes in polymerase complex of Newcastle disease virus.

    Science.gov (United States)

    Kumar, Chandra Shekhar; Kumar, Sachin

    2017-06-01

    Newcastle disease virus (NDV) is pathogenic to both avian and non-avian species but extensively finds poultry as its primary host and causes heavy economic losses in the poultry industry. In this study, a total of 186 polymerase complex comprising of nucleoprotein (N), phosphoprotein (P), and large polymerase (L) genes of NDV was analyzed for synonymous codon usage. The relative synonymous codon usage and effective number of codons (ENC) values were used to estimate codon usage variation in each gene. Correspondence analysis (COA) was used to study the major trend in codon usage variation. Analyzing the ENC plot values against GC3s (at synonymous third codon position) we concluded that mutational pressure was the main factor determining codon usage bias than translational selection in NDV N, P, and L genes. Moreover, correlation analysis indicated, that aromaticity of N, P, and L genes also influenced the codon usage variation. The varied distribution of pathotypes for N, P, and L gene clearly suggests that change in codon usage for NDV is pathotype specific. The codon usage preference similarity in N, P, and L gene might be detrimental for polymerase complex functioning. The study represents a comprehensive analysis to date of N, P, and L genes codon usage pattern of NDV and provides a basic understanding of the mechanisms for codon usage bias. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Comparative characterization analysis of synonymous codon usage bias in classical swine fever virus.

    Science.gov (United States)

    Xu, Xin; Fei, Dongliang; Han, Huansheng; Liu, Honggui; Zhang, Jiayong; Zhou, Yulong; Xu, Chuang; Wang, Hongbin; Cao, Hongwei; Zhang, Hua

    2017-06-01

    Classical swine fever virus (CSFV) is responsible for the highly contagious viral disease of swine, and causes great economic loss in the swine-raising industry. Considering the significance of CSFV, a systemic analysis was performed to study its codon usage patterns. In this study, using the complete genome sequences of 76 CSFV representing three genotypes, we firstly analyzed the relative nucleotide composition, effective number of codon (ENC) and synonymous codon usage in CSFV genomes. The results showed that CSFV is GC-moderate genome and the third-ended codons are not preferentially used. Every ENC values in CSFV genomes are >50, indicating that the codon usage bias is comparatively slight. Subsequently, we performed the correspondence analysis (COA) to investigate synonymous codon usage variation among all of the CSFV genomes. We found that codon usage bias in these CSFV genomes is greatly influenced by G + C mutation, which suggests that mutational pressure may be the main factor determining the codon usage biases. Moreover, most of the codon usage bias among different CSFV ORFs is directly related to the nucleotide composition. Other factors, such as hydrophobicity and aromaticity, also influence the codon usage variation among CSFV genomes. Our study represents the most comprehensive analysis of codon usage patterns in CSFV genome and provides a basic understanding of the mechanisms for its codon usage bias. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Comparative genomic analysis for nucleotide, codon, and amino acid usage patterns of mycoplasmas.

    Science.gov (United States)

    Ma, Xiao-Xia; Cao, Xin; Ma, Peng; Chang, Qiu-Yan; Li, Lin-Jie; Zhou, Xiao-Kai; Zhang, De-Rong; Li, Ming-Sheng; Ma, Zhong-Ren

    2018-03-14

    The evolutionary factors in influencing the genetic characteristics of nucleotide, synonymous codon, and amino acid usage of 18 mycoplasma species were analyzed. The nucleotide usage at the 1st and 2nd codon position which determines amino acid composition of proteins has a significant correlation with the total nucleotide composition of gene population of these mycoplasma species, however, the nucleotide usage at the 3rd codon position which affects synonymous codon usage patterns has a slight correlation with either the total nucleotide composition or the nucleotide usage at the 1st and 2nd codon position. Other evolutionary factors join in the evolutionary process of mycoplasma apart from mutation pressure caused by nucleotide usage constraint based on the relationships between effective number of codons/codon adaptation index and nucleotide usage at the 3rd codon position. Although nucleotide usage of gene population in mycoplasma dominates in forming the overall codon usage trends, the relative abundance of codon with nucleotide context and amino acid usage pattern show that translation selection involved in translation accuracy and efficiency play an important role in synonymous codon usage patterns. In addition, synonymous codon usage patterns of gene population have a bigger power to represent genetic diversity among different species than amino acid usage. These results suggest that although the mycoplasmas reduce its genome size during the evolutionary process and shape the form, which is opposite to their hosts, of AT usages at high levels, this kind organism still depends on nucleotide usage at the 1st and 2nd codon positions to control syntheses of the requested proteins for surviving in their hosts and nucleotide usage at the 3rd codon position to develop genetic diversity of different mycoplasma species. This systemic analysis with 18 mycoplasma species may provide useful clues for further in vivo genetic studies on the related species. © 2018 WILEY

  1. A Comprehensive Analysis of Codon Usage Patterns in Blunt Snout Bream (Megalobrama amblycephala Based on RNA-Seq Data

    Directory of Open Access Journals (Sweden)

    Xiaoke Duan

    2015-05-01

    Full Text Available Blunt snout bream (Megalobrama amblycephala is an important fish species for its delicacy and high economic value in China. Codon usage analysis could be helpful to understand its codon biology, mRNA translation and vertebrate evolution. Based on RNA-Seq data for M. amblycephala, high-frequency codons (CUG, AGA, GUG, CAG and GAG, as well as low-frequency ones (NUA and NCG codons were identified. A total of 724 high-frequency codon pairs were observed. Meanwhile, 14 preferred and 199 avoided neighboring codon pairs were also identified, but bias was almost not shown with one or more intervening codons inserted between the same pairs. Codon usage bias in the regions close to start and stop codons indicated apparent heterogeneity, which even occurs in the flanking nucleotide sequence. Codon usage bias (RSCU and SCUO was related to GC3 (GC content of 3rd nucleotide in codon bias. Six GO (Gene ontology categories and the number of methylation targets were influenced by GC3. Codon usage patterns comparison among 23 vertebrates showed species specificities by using GC contents, codon usage and codon context analysis. This work provided new insights into fish biology and new information for breeding projects.

  2. Analysis of transcriptome data reveals multifactor constraint on codon usage in Taenia multiceps.

    Science.gov (United States)

    Huang, Xing; Xu, Jing; Chen, Lin; Wang, Yu; Gu, Xiaobin; Peng, Xuerong; Yang, Guangyou

    2017-04-20

    Codon usage bias (CUB) is an important evolutionary feature in genomes that has been widely observed in many organisms. However, the synonymous codon usage pattern in the genome of T. multiceps remains to be clarified. In this study, we analyzed the codon usage of T. multiceps based on the transcriptome data to reveal the constraint factors and to gain an improved understanding of the mechanisms that shape synonymous CUB. Analysis of a total of 8,620 annotated mRNA sequences from T. multiceps indicated only a weak codon bias, with mean GC and GC3 content values of 49.29% and 51.43%, respectively. Our analysis indicated that nucleotide composition, mutational pressure, natural selection, gene expression level, amino acids with grand average of hydropathicity (GRAVY) and aromaticity (Aromo) and the effective selection of amino-acids all contributed to the codon usage in T. multiceps. Among these factors, natural selection was implicated as the major factor affecting the codon usage variation in T. multiceps. The codon usage of ribosome genes was affected mainly by mutations, while the essential genes were affected mainly by selection. In addition, 21codons were identified as "optimal codons". Overall, the optimal codons were GC-rich (GC:AU, 41:22), and ended with G or C (except CGU). Furthermore, different degrees of variation in codon usage were found between T. multiceps and Escherichia coli, yeast, Homo sapiens. However, little difference was found between T. multiceps and Taenia pisiformis. In this study, the codon usage pattern of T. multiceps was analyzed systematically and factors affected CUB were also identified. This is the first study of codon biology in T. multiceps. Understanding the codon usage pattern in T. multiceps can be helpful for the discovery of new genes, molecular genetic engineering and evolutionary studies.

  3. Numerical analysis of dependence between adapted mesh and assumed error indicator

    Science.gov (United States)

    Kucwaj, Jan

    2018-01-01

    The paper considers the influence of the assumed error indicator on the final adapted mesh. Provided that threshold values of an error are increased by applying the adaptive procedure, it turns out that final mesh depends on the assumed error indicator. In the paper, there were used the standard error estimates and the error indicator proposed by the author. The proposed error indicator is based on applying hierarchically generalized finite difference method (FDM). In the case of the proposed error indicator, the final adapted mesh is the most optimal for the exact solution.

  4. Changes in body temperature pattern in vertebrates do not influence the codon usages of alpha-globin genes.

    Science.gov (United States)

    Hamada, Kazuo; Horiike, Tokumasa; Kanaya, Shigehiko; Nakamura, Hiroshi; Ota, Hidetoshi; Yatogo, Takayuki; Okada, Kazuhisa; Nakamura, Hiroshi; Shinozawa, Takao

    2002-06-01

    Codon usages are known to vary among vertebrates chiefly due to variations in isochore structure. Under the assumption that marked differences exist in isochore structure between warm-blooded and cold-blooded animals, the variations among vertebrates were previously attributed to an adaptation to homeothermy. However, based on data from a turtle species and a crocodile (Archosauromorpha), it was recently proposed that the common ancestors of mammals, birds and extent reptiles already had the "warm-blooded" isochore structure. We determined the nucleotide sequences of alpha-globin genes from two species of heterotherms, cuckoo (Cuculus canorus) and bat (Pipistrellus abramus), and three species of snakes (Lepidosauromorpha), Naja kaouthia from a tropical terrestrial habitat, Elaphe climacophora from a temperate terrestrial habitat, and Hydrophis melanocephalus from a tropical marine habitat. Our purposes were to assess the influence of differential body temperature patterns on codon usage and GC content at the third position of a codon (GC3), and to test the hypothesis concerning the phylogenetic position at which GC contents had increased in vertebrates. The results of principal component analysis (PCA) using the present data and data for other taxa from GenBank indicate that the primary difference in codon usage in globin genes among amniotes and other vertebrates lies in GC3. The codon usages (and GC3) in alpha-globin genes from two heterotherms and three snakes are similar to those in alpha-globin genes from warm-blooded vertebrates. These results refute the influence of body temperature pattern upon codon usages (and GC3) in alpha-globin genes, and support the hypothesis that the increase in GC content in the genome occurred in the common ancestor of amniotes.

  5. Sustainability indicators : A tool to generate learning and adaptation in sustainable urban development

    NARCIS (Netherlands)

    Pupphachai, Umaporn; Zuidema, Christian

    The pursuit of sustainable development as an adaptive process of learning-by-doing may benefit from using sustainability indicators (Sis). Nevertheless, adaptive governance may demand more from SIs than what these indicators can currently deliver. In response, we identify three conditioning factors

  6. Comparative analysis of codon usage bias and codon context patterns between dipteran and hymenopteran sequenced genomes.

    Directory of Open Access Journals (Sweden)

    Susanta K Behura

    Full Text Available BACKGROUND: Codon bias is a phenomenon of non-uniform usage of codons whereas codon context generally refers to sequential pair of codons in a gene. Although genome sequencing of multiple species of dipteran and hymenopteran insects have been completed only a few of these species have been analyzed for codon usage bias. METHODS AND PRINCIPAL FINDINGS: Here, we use bioinformatics approaches to analyze codon usage bias and codon context patterns in a genome-wide manner among 15 dipteran and 7 hymenopteran insect species. Results show that GAA is the most frequent codon in the dipteran species whereas GAG is the most frequent codon in the hymenopteran species. Data reveals that codons ending with C or G are frequently used in the dipteran genomes whereas codons ending with A or T are frequently used in the hymenopteran genomes. Synonymous codon usage orders (SCUO vary within genomes in a pattern that seems to be distinct for each species. Based on comparison of 30 one-to-one orthologous genes among 17 species, the fruit fly Drosophila willistoni shows the least codon usage bias whereas the honey bee (Apis mellifera shows the highest bias. Analysis of codon context patterns of these insects shows that specific codons are frequently used as the 3'- and 5'-context of start and stop codons, respectively. CONCLUSIONS: Codon bias pattern is distinct between dipteran and hymenopteran insects. While codon bias is favored by high GC content of dipteran genomes, high AT content of genes favors biased usage of synonymous codons in the hymenopteran insects. Also, codon context patterns vary among these species largely according to their phylogeny.

  7. Adaptive capacity indicators to assess sustainability of urban water systems - Current application.

    Science.gov (United States)

    Spiller, Marc

    2016-11-01

    Sustainability is commonly assessed along environmental, societal, economic and technological dimensions. A crucial aspect of sustainability is that inter-generational equality must be ensured. This requires that sustainability is attained in the here and now as well as into the future. Therefore, what is perceived as 'sustainable' changes as a function of societal opinion and technological and scientific progress. A concept that describes the ability of systems to change is adaptive capacity. Literature suggests that the ability of systems to adapt is an integral part of sustainable development. This paper demonstrates that indicators measuring adaptive capacity are underrepresented in current urban water sustainability studies. Furthermore, it is discussed under which sustainability dimensions adaptive capacity indicators are lacking and why. Of the >90 indicators analysed, only nine are adaptive capacity indicators, of which six are socio-cultural, two technological, one economical and none environmental. This infrequent use of adaptive capacity indicators in sustainability assessments led to the conclusion that the challenge of dynamic and uncertain urban water systems is, with the exception of the socio-cultural dimension, not yet sufficiently reflected in the application of urban water sustainability indicators. This raises concerns about the progress towards urban water systems that can transform as a response variation and change. Therefore, research should focus on developing methods and indicators that can define, evaluate and quantify adaptive capacity under the economic, environmental and technical dimension of sustainability. Furthermore, it should be evaluated whether sustainability frameworks that focus on the control processes of urban water systems are more suitable for measuring adaptive capacity, than the assessments along environmental, economic, socio-cultural and technological dimensions. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Establishment of an indicator concept for the German strategy on adaptation to climate change

    Energy Technology Data Exchange (ETDEWEB)

    Schoenthaler, Konstanze; Andrian-Werburg, Stefan von; Wulfert, Katrin [Bosch und Partner GmbH, Muenchen (Germany); Luthardt, Vera; Kreinsen, Beatrice; Schultz-Sternberg, R.; Hommel, Robert [Hochschule fuer Nachhaltige Entwicklung Eberswalde (Germany)

    2010-11-15

    Even if we succeed in achieving the EU target of reducing global warming to 2 C, it will be absolutely essential to adapt to changing climatic conditions. The greenhouse gases currently present in the atmosphere will influence the climate in coming decades. The day on which it is quite clear which climatic scenario prevails, so that it is possible to model all relevant processes down to regional level, will be the day on which it is too late to adapt to the actual scenario. Our endeavours to adapt to climate change do not mean, however, that we can neglect to take measures in order to reduce the output of greenhouse gases. It is important to remember that on their own, neither adaptation nor mitigation can prevent the grave impacts resulting from climate change. In fact, they complement each other meaningfully thus helping to alleviate the risks of climate change. On 17th December 2008 the German Federal Cabinet adopted the DAS (German Strategy for the Adaptation to Climate Change), (Bundesregierung 2008). The DAS has created the framework for adapting to the consequences of climate change in Germany. First and fore-most, the DAS contributes its guidelines at Federal level, to provide a guideline for agents at other levels. The Strategy lays the foundation for a medium-term process. In conjunction with the individual Federal States and other groups representing various sectors of society, the Strategy provides a step-by-step assessment of the risks of climate change. Furthermore, it states the potential requirements for action, and defines the appropriate goals and potential adaptation measures to be developed and implemented in this process. In due course, the Federal Environment Agency (UBA) will design a comprehensive set of tools to support and advance the DAS. An integral part of this will be the Special Information System 'Adaptation' (FISKA) and an Indicator System to aid adaptation. The latter is one of the key tasks identified for the DAS. As far

  9. Analysis of codon usage patterns in Ginkgo biloba reveals codon usage tendency from A/U-ending to G/C-ending

    Science.gov (United States)

    He, Bing; Dong, Hui; Jiang, Cong; Cao, Fuliang; Tao, Shentong; Xu, Li-an

    2016-01-01

    As one of the most ancient tree species, the codon usage pattern analysis of Ginkgo biloba is a useful way to understand its evolutionary and genetic mechanisms. Several studies have been conducted on angiosperms, but seldom on gymnosperms. Based on RNA-Seq data of the G. biloba transcriptome, amount to 17,579 unigenes longer than 300 bp were selected and analyzed from 68,547 candidates. The codon usage pattern tended towards more frequently use of A/U-ending codons, which showed an obvious gradient progressing from gymnosperms to dicots to monocots. Meanwhile, analysis of high/low-expression unigenes revealed that high-expression unigenes tended to use G/C-ending codons together with more codon usage bias. Variation of unigenes with different functions suggested that unigenes involving in environment adaptation use G/C-ending codons more frequently with more usage bias, and these results were consistent with the conclusion that the formation of G. biloba codon usage bias was dominated by natural selection. PMID:27808241

  10. P-value based visualization of codon usage data

    Directory of Open Access Journals (Sweden)

    Fricke Wolfgang

    2006-06-01

    Full Text Available Abstract Two important and not yet solved problems in bacterial genome research are the identification of horizontally transferred genes and the prediction of gene expression levels. Both problems can be addressed by multivariate analysis of codon usage data. In particular dimensionality reduction methods for visualization of multivariate data have shown to be effective tools for codon usage analysis. We here propose a multidimensional scaling approach using a novel similarity measure for codon usage tables. Our probabilistic similarity measure is based on P-values derived from the well-known chi-square test for comparison of two distributions. Experimental results on four microbial genomes indicate that the new method is well-suited for the analysis of horizontal gene transfer and translational selection. As compared with the widely-used correspondence analysis, our method did not suffer from outlier sensitivity and showed a better clustering of putative alien genes in most cases.

  11. Selection on start codons in prokaryotes and potential compensatory nucleotide substitutions.

    Science.gov (United States)

    Belinky, Frida; Rogozin, Igor B; Koonin, Eugene V

    2017-09-29

    Reconstruction of the evolution of start codons in 36 groups of closely related bacterial and archaeal genomes reveals purifying selection affecting AUG codons. The AUG starts are replaced by GUG and especially UUG significantly less frequently than expected under the neutral expectation derived from the frequencies of the respective nucleotide triplet substitutions in non-coding regions and in 4-fold degenerate sites. Thus, AUG is the optimal start codon that is actively maintained by purifying selection. However, purifying selection on start codons is significantly weaker than the selection on the same codons in coding sequences, although the switches between the codons result in conservative amino acid substitutions. The only exception is the AUG to UUG switch that is strongly selected against among start codons. Selection on start codons is most pronounced in evolutionarily conserved, highly expressed genes. Mutation of the start codon to a sub-optimal form (GUG or UUG) tends to be compensated by mutations in the Shine-Dalgarno sequence towards a stronger translation initiation signal. Together, all these findings indicate that in prokaryotes, translation start signals are subject to weak but significant selection for maximization of initiation rate and, consequently, protein production.

  12. Balanced Codon Usage Optimizes Eukaryotic Translational Efficiency

    Science.gov (United States)

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

    2012-01-01

    Cellular efficiency in protein translation is an important fitness determinant in rapidly growing organisms. It is widely believed that synonymous codons are translated with unequal speeds and that translational efficiency is maximized by the exclusive use of rapidly translated codons. Here we estimate the in vivo translational speeds of all sense codons from the budding yeast Saccharomyces cerevisiae. Surprisingly, preferentially used codons are not translated faster than unpreferred ones. We hypothesize that this phenomenon is a result of codon usage in proportion to cognate tRNA concentrations, the optimal strategy in enhancing translational efficiency under tRNA shortage. Our predicted codon–tRNA balance is indeed observed from all model eukaryotes examined, and its impact on translational efficiency is further validated experimentally. Our study reveals a previously unsuspected mechanism by which unequal codon usage increases translational efficiency, demonstrates widespread natural selection for translational efficiency, and offers new strategies to improve synthetic biology. PMID:22479199

  13. Analysis of synonymous codon usage in Zika virus.

    Science.gov (United States)

    Hussain, Snawar; Rasool, Sahibzada Tasleem

    2017-09-01

    Zika virus is a zoonotic pathogen, which have made frequent incursion into the human population in Africa and South East Asia over the course of several decades but never reached to the pandemic proportions until the most recent outbreak. Viruses are solely dependent on host synthetic machinery for their replication cycle; therefore, replication and persistence in a host species of different genetic background requires certain degree of adaptation. These adaptations are necessary to avoid detection from host immune surveillance and maximize the utilization of available resources for efficient viral replication. Study of genomic composition and codon usage pattern not only offer an insight into the adaptation of viruses to their new host, but may also provide some information about pathogenesis and spread of the virus. To elucidate the genetic features and synonymous codon usage bias in ZIKV genome, a comprehensive analysis was performed on 80 full-length ZIKV sequences. Our analyses shows that the overall extent of codon usage bias in ZIKV genome is low and affected by nucleotide composition, protein properties, natural selection, and gene expression level. Copyright © 2017. Published by Elsevier B.V.

  14. Phylogenetic inference with weighted codon evolutionary distances.

    Science.gov (United States)

    Criscuolo, Alexis; Michel, Christian J

    2009-04-01

    We develop a new approach to estimate a matrix of pairwise evolutionary distances from a codon-based alignment based on a codon evolutionary model. The method first computes a standard distance matrix for each of the three codon positions. Then these three distance matrices are weighted according to an estimate of the global evolutionary rate of each codon position and averaged into a unique distance matrix. Using a large set of both real and simulated codon-based alignments of nucleotide sequences, we show that this approach leads to distance matrices that have a significantly better treelikeness compared to those obtained by standard nucleotide evolutionary distances. We also propose an alternative weighting to eliminate the part of the noise often associated with some codon positions, particularly the third position, which is known to induce a fast evolutionary rate. Simulation results show that fast distance-based tree reconstruction algorithms on distance matrices based on this codon position weighting can lead to phylogenetic trees that are at least as accurate as, if not better, than those inferred by maximum likelihood. Finally, a well-known multigene dataset composed of eight yeast species and 106 codon-based alignments is reanalyzed and shows that our codon evolutionary distances allow building a phylogenetic tree which is similar to those obtained by non-distance-based methods (e.g., maximum parsimony and maximum likelihood) and also significantly improved compared to standard nucleotide evolutionary distance estimates.

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

    NARCIS (Netherlands)

    Rouwendal, G.J.A.; Mendes, O.; Wolbert, E.J.H.; Boer, de A.D.

    1997-01-01

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

  16. Codes in the codons: construction of a codon/amino acid periodic table and a study of the nature of specific nucleic acid-protein interactions.

    Science.gov (United States)

    Benyo, B; Biro, J C; Benyo, Z

    2004-01-01

    The theory of "codon-amino acid coevolution" was first proposed by Woese in 1967. It suggests that there is a stereochemical matching - that is, affinity - between amino acids and certain of the base triplet sequences that code for those amino acids. We have constructed a common periodic table of codons and amino acids, where the nucleic acid table showed perfect axial symmetry for codons and the corresponding amino acid table also displayed periodicity regarding the biochemical properties (charge and hydrophobicity) of the 20 amino acids and the position of the stop signals. The table indicates that the middle (2/sup nd/) amino acid in the codon has a prominent role in determining some of the structural features of the amino acids. The possibility that physical contact between codons and amino acids might exist was tested on restriction enzymes. Many recognition site-like sequences were found in the coding sequences of these enzymes and as many as 73 examples of codon-amino acid co-location were observed in the 7 known 3D structures (December 2003) of endonuclease-nucleic acid complexes. These results indicate that the smallest possible units of specific nucleic acid-protein interaction are indeed the stereochemically compatible codons and amino acids.

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

    Science.gov (United States)

    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.

  18. Nucleotide composition bias and codon usage trends of gene ...

    Indian Academy of Sciences (India)

    Compared with the codon usage of ovine, Mycoplasma capricolum and M. agalactiae tend to select optimal codons, which are rare codons in ovine. Due to codon usage pattern caused by genes with key biological functions, the overall codon usage trends represent a certain evolutionary direction in the life cycle of the two ...

  19. Codon optimizing for increased membrane protein production

    DEFF Research Database (Denmark)

    Mirzadeh, K.; Toddo, S.; Nørholm, Morten

    2016-01-01

    Reengineering a gene with synonymous codons is a popular approach for increasing production levels of recombinant proteins. Here we present a minimalist alternative to this method, which samples synonymous codons only at the second and third positions rather than the entire coding sequence...

  20. The “codon impact parameter”

    Indian Academy of Sciences (India)

    Unknown

    ribulose 1,5-bisphosphate carboxylase oxygenase (RuBisCO), to get the codon usage pattern. The score codon-impact-parameter (CIP) is proposed. In the space of these scores the distance metric is defined and then used to estimate relations ...

  1. Analysis of codon usage pattern of mitochondrial protein-coding genes in different hookworms.

    Science.gov (United States)

    Deb, Bornali; Uddin, Arif; Mazumder, Gulshana Akthar; Chakraborty, Supriyo

    2018-01-01

    The phenomenon of unequal usage of synonymous codons encoding an amino acid in which some codons are more preferred to others is the codon usage bias (CUB) and it is species specific. Analysis of CUB helps in understanding evolution at molecular level and acquires significance in mRNA translation, design of transgenes and new gene discovery. In our current study, we analyzed synonymous codon usage pattern and the factors influencing it on mitochondrial protein coding genes of 6 different hookworms i.e. Ancylostoma ceylanicum, Ancylostoma duodenale, Necator americanus, Ancylostoma tubaeforme, Ancylostoma caninum and Uncinaria sanguinis as no work was reported yet. The effective number of codons for mitochondrial genes suggested that codon usage bias was high in most species. The GC content was lower than AT content i.e. genes were AT rich as indicated by nucleotide composition analysis. The overall nucleotide composition along with its composition at 3rd codon position and correspondence analysis suggested that both natural selection and mutation pressure might have affected the codon usage bias in mitochondrial genes. However, neutrality plot revealed that mutation pressure might have played a major role in A. ceylanicum while natural selection might have played the dominant role in Ancylostoma duodenale, Necator americanus, Ancylostoma tubaeforme, Ancylostoma caninum and Uncinaria sanguinis. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Berendonk Thomas U

    2011-05-01

    Full Text Available Abstract Background Despite the fact that the organization of the ciliate mitochondrial genome is exceptional, only few ciliate mitochondrial genomes have been sequenced until today. All ciliate mitochondrial genomes are linear. They are 40 kb to 47 kb long and contain some 50 tightly packed genes without introns. Earlier studies documented that the mitochondrial guanine + cytosine contents are very different between Paramecium tetraurelia and all studied Tetrahymena species. This raises the question of whether the high mitochondrial G+C content observed in P. tetraurelia is a characteristic property of Paramecium mtDNA, or whether it is an exception of the ciliate mitochondrial genomes known so far. To test this question, we determined the mitochondrial genome sequence of Paramecium caudatum and compared the gene content and sequence properties to the closely related P. tetraurelia. Results The guanine + cytosine content of the P. caudatum mitochondrial genome was significantly lower than that of P. tetraurelia (22.4% vs. 41.2%. This difference in the mitochondrial nucleotide composition was accompanied by significantly different codon usage patterns in both species, i.e. within P. caudatum clearly A/T ending codons dominated, whereas for P. tetraurelia the synonymous codons were more balanced with a higher number of G/C ending codons. Further analyses indicated that the nucleotide composition of most members of the genus Paramecium resembles that of P. caudatum and that the shift observed in P. tetraurelia is restricted to the P. aurelia species complex. Conclusions Surprisingly, the codon usage bias in the P. caudatum mitochondrial genome, exemplified by the effective number of codons, is more similar to the distantly related T. pyriformis and other single-celled eukaryotes such as Chlamydomonas, than to the closely related P. tetraurelia. These differences in base composition and codon usage bias were, however, not reflected in the amino

  3. Evidence-based practice: a quality indicator analysis of peer-tutoring in adapted physical education.

    Science.gov (United States)

    Kalef, Laura; Reid, Greg; Macdonald, Cathy

    2013-09-01

    The purpose of the research was to conduct a quality indicator analysis of studies investigating peer-tutoring for students with a disability in adapted physical education. An electronic search was conducted among English journals published from 1960 to November 2012. Databases included ERIC, PsycINFO, and SPORTDiscus. Fifteen research studies employing group-experimental (Gersten et al., 2005) or single-subject designs (Horner et al., 2005) met inclusion criteria. Each study was assessed for the presence and clarity of quality indicators. Group designs met an average of 62.5% essential and 69% desirable indicators. An average of 80% of indicators was present for single-subject designs. Results suggest claims of peer-tutoring being an evidence-based practice are premature. Recommendations for clarifying and applying the quality indicators are offered. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Metabolic Disorders in the Transition Period Indicate that the Dairy Cows’ Ability to Adapt is Overstressed

    Science.gov (United States)

    Sundrum, Albert

    2015-01-01

    Simple Summary Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. Problems derive from difficulties animals have to adapt to large variations and disturbances occurring both outside and inside the organism. A lack of success in solving these issues may be due to predominant approaches in farm management and agricultural science, dealing with such disorders as merely negative side effects. Instead, a successful adaptation of animals to their living conditions should be seen as an important end in itself. Both farm management and agricultural sciences should support animals in their ability to cope with nutritional and metabolic challenges by employing a functional and result-driven approach. Abstract Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes and their large variations on various scales

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

    DEFF Research Database (Denmark)

    Frenkel-Morgenstern, Milana; Danon, Tamar; Christian, Thomas

    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...... 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...

  6. Correlation matrix for quartet codon usage

    CERN Document Server

    Frappat, L; Sorba, Paul

    2005-01-01

    It has been argued that the sum of usage probabilities for codons, belonging to quartets, that have as third nucleotide C or A, is independent of the biological species for vertebrates. The comparison between the theoretical correlation matrix derived from these sum rules and the experimentally computed matrix for 26 species shows a satisfactory agreement. The Shannon entropy, weakly depending on the biological species, gives further support. Suppression of codons containing the dinucleotides CG or AU is put in evidence.

  7. A single sequence context cannot satisfy all non-AUG initiator codons in yeast†

    Directory of Open Access Journals (Sweden)

    Wang Tzu-Ling

    2010-07-01

    Full Text Available Abstract Background Previous studies in Saccharomyces cerevisiae showed that ALA1 (encoding alanyl-tRNA synthetase and GRS1 (encoding glycyl-tRNA synthetase respectively use ACG and TTG as their alternative translation initiator codons. To explore if any other non-ATG triplets can act as initiator codons in yeast, ALA1 was used as a reporter for screening. Results We show herein that except for AAG and AGG, all triplets that differ from ATG by a single nucleotide were able to serve as initiator codons in ALA1. Among these initiator codons, TTG, CTG, ACG, and ATT had ~50% initiating activities relative to that of ATG, while GTG, ATA, and ATC had ~20% initiating activities relative to that of ATG. Unexpectedly, these non-AUG initiator codons exhibited different preferences toward various sequence contexts. In particular, GTG was one of the most efficient non-ATG initiator codons, while ATA was essentially inactive in the context of GRS1. Conclusion This finding indicates that a sequence context that is favorable for a given non-ATG initiator codon might not be as favorable for another.

  8. Comorbidity indices for clinical trials: adaptation of two existing indices for use with the FREEDOM trial in women with postmenopausal osteoporosis.

    Science.gov (United States)

    Silverman, S L; Wang, A; Cheng, L; Yang, Y; Libanati, C; Geller, M; Grauer, A; Nevitt, M; Revicki, D; Viswanathan, H N

    2016-01-01

    Two comorbidity indices were adapted for use in the FREEDOM trial and significantly correlated with the number of medications and impaired health status at baseline. The indices have applications for the analysis of clinical trial data and would allow for the appropriate adjustment of comorbidities when evaluating clinical trial outcomes. The purpose of this study is to adapt two published comorbidity indices for use with the FREEDOM clinical trial evaluating postmenopausal women with osteoporosis. FREEDOM enrolled women aged 60-90 years with a bone mineral density T-score <-2.5 at the lumbar spine or total hip and ≥-4.0 at both sites. Comorbidity indices were calculated using methods described by Sangha (Arthritis Rheum 49:156-163, 2003) and Wolfe (J Rheumatol 37:305-315, 2010) following modification. The adapted Sangha index included 12 conditions with a summary score of 0-12; the adapted Wolfe index included 7 conditions with a weighted summary score of 0-8. Higher scores indicated greater comorbidity. A panel of clinicians independently reviewed subjects' medical histories using a systematic process based on Medical Dictionary for Regulatory Activities (MedDRA) preferred terms to map specified comorbid conditions. Spearman correlations between the adapted indices and baseline subject characteristics expected to be associated with comorbidities were examined. Of the 7808 subjects in this study, 74 % had ≥1 comorbidities based on the adapted Sangha or Wolfe comorbidity indices. The mean (SD) adapted Sangha and Wolfe comorbidity indices were 1.4 (1.2) and 1.4 (1.3), respectively. Both indices correlated positively with age, body mass index, and the number of medications (r = 0.54 to 0.55) at baseline and inversely correlated with health-related quality of life (r = -0.22 to -0.30) (all P < 0.0001). Further, when either the adapted Sangha or Wolfe index was included as a covariate for assessing mortality over 36 months in the FREEDOM population, the

  9. A codon window in mRNA downstream of the initiation codon where NGG codons give strongly reduced gene expression in Escherichia coli

    DEFF Research Database (Denmark)

    Gonzalez de Valdivia, Ernesto I; Isaksson, Leif A

    2004-01-01

    The influences on gene expression by codons at positions +2, +3, +5 and +7 downstream of the initiation codon have been compared. Most of the +2 codons that are known to give low gene expression are associated with a higher expression if placed at the later positions. The NGG codons AGG, CGG, UGG...... and GGG, but not GGN or GNG (where N is non-G), are unique since they are associated with a very low gene expression also if located at positions +2, +3 and +5. All codons, including NGG, give a normal gene expression if placed at positions +7. The negative effect by the NGG codons is true for both...

  10. Efficient Reassignment of a Frequent Serine Codon in Wild-Type Escherichia coli.

    Science.gov (United States)

    Ho, Joanne M; Reynolds, Noah M; Rivera, Keith; Connolly, Morgan; Guo, Li-Tao; Ling, Jiqiang; Pappin, Darryl J; Church, George M; Söll, Dieter

    2016-02-19

    Expansion of the genetic code through engineering the translation machinery has greatly increased the chemical repertoire of the proteome. This has been accomplished mainly by read-through of UAG or UGA stop codons by the noncanonical aminoacyl-tRNA of choice. While stop codon read-through involves competition with the translation release factors, sense codon reassignment entails competition with a large pool of endogenous tRNAs. We used an engineered pyrrolysyl-tRNA synthetase to incorporate 3-iodo-l-phenylalanine (3-I-Phe) at a number of different serine and leucine codons in wild-type Escherichia coli. Quantitative LC-MS/MS measurements of amino acid incorporation yields carried out in a selected reaction monitoring experiment revealed that the 3-I-Phe abundance at the Ser208AGU codon in superfolder GFP was 65 ± 17%. This method also allowed quantification of other amino acids (serine, 33 ± 17%; phenylalanine, 1 ± 1%; threonine, 1 ± 1%) that compete with 3-I-Phe at both the aminoacylation and decoding steps of translation for incorporation at the same codon position. Reassignments of different serine (AGU, AGC, UCG) and leucine (CUG) codons with the matching tRNA(Pyl) anticodon variants were met with varying success, and our findings provide a guideline for the choice of sense codons to be reassigned. Our results indicate that the 3-iodo-l-phenylalanyl-tRNA synthetase (IFRS)/tRNA(Pyl) pair can efficiently outcompete the cellular machinery to reassign select sense codons in wild-type E. coli.

  11. Codon 201Gly Polymorphic Type of the DCC Gene is Related to Disseminated Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Xiao-Tang Kong

    2001-01-01

    Full Text Available The deleted in colorectal carcinoma (DCC gene is a potential tumor- suppressor gene on chromosome 18821.3. The relatively high frequency of loss of heterozygosity (LOH and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg to GGA (Gly at codon 201 resulting in three types of polymorphism: codon 201Gly type, codon 201Arg/Gly type, and codon 201Arg type. The codon 201Gly type occurred more frequently in disseminated (stages IV and IVs neuroblastomas (72% than in localized (stages I, II, and III tumors (48% (P=.035, and normal controls (38% (P=.024. In addition, the codon 201Gly type was significantly more common in tumors found clinically (65% than in those found by mass screening (35% (P=.002. The results suggested that the codon 201Gly type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.

  12. Selfing in Haploid Plants and Efficacy of Selection: Codon Usage Bias in the Model Moss Physcomitrella patens.

    Science.gov (United States)

    Szövényi, Péter; Ullrich, Kristian K; Rensing, Stefan A; Lang, Daniel; van Gessel, Nico; Stenøien, Hans K; Conti, Elena; Reski, Ralf

    2017-06-01

    A long-term reduction in effective population size will lead to major shift in genome evolution. In particular, when effective population size is small, genetic drift becomes dominant over natural selection. The onset of self-fertilization is one evolutionary event considerably reducing effective size of populations. Theory predicts that this reduction should be more dramatic in organisms capable for haploid than for diploid selfing. Although theoretically well-grounded, this assertion received mixed experimental support. Here, we test this hypothesis by analyzing synonymous codon usage bias of genes in the model moss Physcomitrella patens frequently undergoing haploid selfing. In line with population genetic theory, we found that the effect of natural selection on synonymous codon usage bias is very weak. Our conclusion is supported by four independent lines of evidence: 1) Very weak or nonsignificant correlation between gene expression and codon usage bias, 2) no increased codon usage bias in more broadly expressed genes, 3) no evidence that codon usage bias would constrain synonymous and nonsynonymous divergence, and 4) predominant role of genetic drift on synonymous codon usage predicted by a model-based analysis. These findings show striking similarity to those observed in AT-rich genomes with weak selection for optimal codon usage and GC content overall. Our finding is in contrast to a previous study reporting adaptive codon usage bias in the moss P. patens. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. RESEARCH ARTICLE Codon usage vis-a-vis start and stop codon ...

    Indian Academy of Sciences (India)

    Prosen

    , for the amino acid lysine, AAG showed almost similar usage frequency to its synonymous partner AAA. (favored codon). The exceptional RSCU score of these two G-ending codons may be due to the presence of TpT and ApA dinucleotides.

  14. Codon usage vis-a-vis start and stop codon context analysis of three ...

    Indian Academy of Sciences (India)

    To understand the variation in genomic composition and its effect on codon usage, we performed the comparative analysis of codon usage and nucleotide usage in the genes of three dicots, Glycine max, Arabidopsis thaliana and Medicago truncatula. The dicot genes were found to be A/T rich and have predominantly ...

  15. Codon usage vis-a-vis start and stop codon context analysis of three ...

    Indian Academy of Sciences (India)

    Prosenjit Paul

    2018-02-20

    Feb 20, 2018 ... from prokaryotes to eukaryotes. Some organisms (Candida albicans and related .... ∑na b gab na, where gab is the observed number of the ath codon for the bth amino acid which has na kinds of ...... Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: a proposal ...

  16. Social and Academic Support and Adaptation to College: Exploring the Relationships between Indicators' College Students

    Science.gov (United States)

    Turkpour, Azita; Mehdinezhad, Vali

    2016-01-01

    The aim of this study was to demonstrate the relation between social and academic support on student ability to adapt to college. Results demonstrated a weak and reverse relation between expression of support and personal ability to adapt and total adaptation. A direct relation was determined between emotional support and social adaptation and…

  17. Universality and Shannon entropy of codon usage

    CERN Document Server

    Frappat, L; Sciarrino, A; Sorba, Paul

    2003-01-01

    The distribution functions of the codon usage probabilities, computed over all the available GenBank data, for 40 eukaryotic biological species and 5 chloroplasts, do not follow a Zipf law, but are best fitted by the sum of a constant, an exponential and a linear function in the rank of usage. For mitochondriae the analysis is not conclusive. A quantum-mechanics-inspired model is proposed to describe the observed behaviour. These functions are characterized by parameters that strongly depend on the total GC content of the coding regions of biological species. It is predicted that the codon usage is the same in all exonic genes with the same GC content. The Shannon entropy for codons, also strongly depending on the exonic GC content, is computed.

  18. Archaeogenetic evidence of ancient nubian barley evolution from six to two-row indicates local adaptation.

    Directory of Open Access Journals (Sweden)

    Sarah A Palmer

    Full Text Available BACKGROUND: Archaeobotanical samples of barley (Hordeum vulgare L. found at Qasr Ibrim display a two-row phenotype that is unique to the region of archaeological sites upriver of the first cataract of the Nile, characterised by the development of distinctive lateral bracts. The phenotype occurs throughout all strata at Qasr Ibrim, which range in age from 3000 to a few hundred years. METHODOLOGY AND FINDINGS: We extracted ancient DNA from barley samples from the entire range of occupancy of the site, and studied the Vrs1 gene responsible for row number in extant barley. Surprisingly, we found a discord between the genotype and phenotype in all samples; all the barley had a genotype consistent with the six-row condition. These results indicate a six-row ancestry for the Qasr Ibrim barley, followed by a reassertion of the two-row condition. Modelling demonstrates that this sequence of evolutionary events requires a strong selection pressure. CONCLUSIONS: The two-row phenotype at Qasr Ibrim is caused by a different mechanism to that in extant barley. The strength of selection required for this mechanism to prevail indicates that the barley became locally adapted in the region in response to a local selection pressure. The consistency of the genotype/phenotype discord over time supports a scenario of adoption of this barley type by successive cultures, rather than the importation of new barley varieties associated with individual cultures.

  19. HEART RATE VARIABILITY AS THE ADAPTATION RESERVE INDICATOR OF CARDIOVASCULAR SYSTEM

    Directory of Open Access Journals (Sweden)

    Aksana Kotava

    2014-12-01

    Full Text Available Background: The efectiveness of the vegetative regulation action might be controlled by the method of heart rate variability (HRV, which has been very popularly used over the last 10 years worldwide. The analysis of many clinical studies indicates that the severity of the disease might be controlled using the method of HRV. Material and methods: All the experimental and controlled group participants, which consisted of healthy students with none sports experience, underwent the examination according to the 5-minute standard protocol of HRV. In addition, all the examinees performed a bicycle stress test. After the bicycle stress test, some additional tests of HRV were also carried out. Results: It was found that some signifcant diferences, between the group of sportsmen and the group of patients, exist. The parasympathetic activity of LF is maximum in athletes and tends to decrease in patients with cardiovascular pathologies. The decreases of the activity of the vasomotor centre was noticed in both study groups. The sympathetic system activity was the lowest in athletes. Conclusions: At the high depression of the vegetative regulation, any signifcant load (physical or psycho-emotional indicates cardiovascular instability which remains beyond the capacity of adaptation. The higher the variability, the more stable the CVS is to the external loads. A sharp decrease of the variability, such as the heart vegetative innervations, causes deteriorating quality of the regulatory mechanisms and, as a result, the risk of cardiovascular diseases increases. Keywords: heart rate variability, deterministic and stochastic loads, cardiovascular system

  20. Codon usage and expression level of human mitochondrial 13 protein coding genes across six continents.

    Science.gov (United States)

    Chakraborty, Supriyo; Uddin, Arif; Mazumder, Tarikul Huda; Choudhury, Monisha Nath; Malakar, Arup Kumar; Paul, Prosenjit; Halder, Binata; Deka, Himangshu; Mazumder, Gulshana Akthar; Barbhuiya, Riazul Ahmed; Barbhuiya, Masuk Ahmed; Devi, Warepam Jesmi

    2017-12-02

    The study of codon usage coupled with phylogenetic analysis is an important tool to understand the genetic and evolutionary relationship of a gene. The 13 protein coding genes of human mitochondria are involved in electron transport chain for the generation of energy currency (ATP). However, no work has yet been reported on the codon usage of the mitochondrial protein coding genes across six continents. To understand the patterns of codon usage in mitochondrial genes across six different continents, we used bioinformatic analyses to analyze the protein coding genes. The codon usage bias was low as revealed from high ENC value. Correlation between codon usage and GC3 suggested that all the codons ending with G/C were positively correlated with GC3 but vice versa for A/T ending codons with the exception of ND4L and ND5 genes. Neutrality plot revealed that for the genes ATP6, COI, COIII, CYB, ND4 and ND4L, natural selection might have played a major role while mutation pressure might have played a dominant role in the codon usage bias of ATP8, COII, ND1, ND2, ND3, ND5 and ND6 genes. Phylogenetic analysis indicated that evolutionary relationships in each of 13 protein coding genes of human mitochondria were different across six continents and further suggested that geographical distance was an important factor for the origin and evolution of 13 protein coding genes of human mitochondria. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  1. Variation in synonymous codon usage in Paenibacillus sp. 32O-W genome.

    Science.gov (United States)

    Deb, Sushanta; Basak, Surajit

    2016-01-01

    Paenibacillus sp. 32O-W, which is attributed for biodesulfurization of petroleum, has 56.34% genomic G+C content. Correspondence analysis on Relative Synonymous Codon Usage (RSCU) of the Paenibacillus sp. 32O-W genome has revealed the two different trends of codon usage variation. Two sets of genes have been identified representing the two distinct pattern of codon usage in this bacterial genome. We have measured several codon usage indices to understand the influencing factors governing the differential pattern of codon usage variation in this bacterial genome. We also observed significant differences in many protein properties between the two gene sets (e.g., hydrophobicity, protein biosynthetic cost, protein aggregation propensity). The compositional difference between the two sets of genes and the difference in their potential gene expressivity are the driving force for the differences in protein biosynthetic cost and aggregation propensity. Based on our results we argue that codon usage variation in Paenibacillus sp. 32O-W genome is actually influenced by both mutational bias and translational selection.

  2. Positive selection in octopus haemocyanin indicates functional links to temperature adaptation.

    Science.gov (United States)

    Oellermann, Michael; Strugnell, Jan M; Lieb, Bernhard; Mark, Felix C

    2015-07-05

    Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the

  3. Future tendencies of climate indicators important for adaptation and mitigation strategies in forestry

    Science.gov (United States)

    Galos, Borbala; Hänsler, Andreas; Gulyas, Krisztina; Bidlo, Andras; Czimber, Kornel

    2014-05-01

    impact analyses and build an important basis of the future adaptation strategies in forestry, agriculture and water management. Funding: The research is supported by the TÁMOP-4.2.2.A-11/1/KONV-2012-0013 and TÁMOP-4.1.1.C-12/1/KONV-2012-0012 (ZENFE) joint EU-national research projects. Keywords: climate indices, climate change impacts, forestry, regional climate modelling

  4. Nucleotide composition bias and codon usage trends of gene ...

    Indian Academy of Sciences (India)

    2015-06-10

    Jun 10, 2015 ... Based on the definition of the translation elongation region of gene (Tuller et al. 2010), we analysed the translation elongation region of genes of M. agalactiae and M. capri- colum as the coding sequence, which is composed of 30 codon positions, ranging from the translation start codon to the 30th codon ...

  5. Codon usage bias analysis for the coding sequences of Camellia ...

    African Journals Online (AJOL)

    sunny t

    2016-02-24

    Feb 24, 2016 ... Codon usage bias plays an important role in the regulation of gene expression. A couple of measures are widely used to quantify the codon usage in genes. On the other hand, no quantitative endeavour has been made to compare the pattern of codon usage diversity within and between different genes of.

  6. Evaluating codon bias perspective in barbiturase gene using ...

    African Journals Online (AJOL)

    Abdullah

    2014-01-08

    Jan 8, 2014 ... Examination of DNA composition along with codon usage was done to reveal dynamics of gene evolution and expression of this enzyme. Key words: Codon usage, barbiturase gene, multivariate statistical analysis. INTRODUCTION. Codon penchant arises in the majority species across all kingdoms and ...

  7. Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

    OpenAIRE

    Kegler-Ebo, D M; Docktor, C M; DiMaio, D

    1994-01-01

    We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequen...

  8. Stop Codon Reassignment in the Wild

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, Natalia [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Schwientek, Patrick [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Tripp, H. James [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Rinke, Christian [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Pati, Amrita [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Huntemann, Marcel [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Visel, Axel [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Woyke, Tanja [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Kyrpides, Nikos [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Rubin, Edward [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.

    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

  9. The Selective Advantage of Synonymous Codon Usage Bias in Salmonella.

    Directory of Open Access Journals (Sweden)

    Gerrit Brandis

    2016-03-01

    Full Text Available The genetic code in mRNA is redundant, with 61 sense codons translated into 20 different amino acids. Individual amino acids are encoded by up to six different codons but within codon families some are used more frequently than others. This phenomenon is referred to as synonymous codon usage bias. The genomes of free-living unicellular organisms such as bacteria have an extreme codon usage bias and the degree of bias differs between genes within the same genome. The strong positive correlation between codon usage bias and gene expression levels in many microorganisms is attributed to selection for translational efficiency. However, this putative selective advantage has never been measured in bacteria and theoretical estimates vary widely. By systematically exchanging optimal codons for synonymous codons in the tuf genes we quantified the selective advantage of biased codon usage in highly expressed genes to be in the range 0.2-4.2 x 10-4 per codon per generation. These data quantify for the first time the potential for selection on synonymous codon choice to drive genome-wide sequence evolution in bacteria, and in particular to optimize the sequences of highly expressed genes. This quantification may have predictive applications in the design of synthetic genes and for heterologous gene expression in biotechnology.

  10. Simulated evolution applied to study the genetic code optimality using a model of codon reassignments.

    Science.gov (United States)

    Santos, José; Monteagudo, Angel

    2011-02-21

    As the canonical code is not universal, different theories about its origin and organization have appeared. The optimization or level of adaptation of the canonical genetic code was measured taking into account the harmful consequences resulting from point mutations leading to the replacement of one amino acid for another. There are two basic theories to measure the level of optimization: the statistical approach, which compares the canonical genetic code with many randomly generated alternative ones, and the engineering approach, which compares the canonical code with the best possible alternative. Here we used a genetic algorithm to search for better adapted hypothetical codes and as a method to guess the difficulty in finding such alternative codes, allowing to clearly situate the canonical code in the fitness landscape. This novel proposal of the use of evolutionary computing provides a new perspective in the open debate between the use of the statistical approach, which postulates that the genetic code conserves amino acid properties far better than expected from a random code, and the engineering approach, which tends to indicate that the canonical genetic code is still far from optimal. We used two models of hypothetical codes: one that reflects the known examples of codon reassignment and the model most used in the two approaches which reflects the current genetic code translation table. Although the standard code is far from a possible optimum considering both models, when the more realistic model of the codon reassignments was used, the evolutionary algorithm had more difficulty to overcome the efficiency of the canonical genetic code. Simulated evolution clearly reveals that the canonical genetic code is far from optimal regarding its optimization. Nevertheless, the efficiency of the canonical code increases when mistranslations are taken into account with the two models, as indicated by the fact that the best possible codes show the patterns of the

  11. Simulated evolution applied to study the genetic code optimality using a model of codon reassignments

    Directory of Open Access Journals (Sweden)

    Monteagudo Ángel

    2011-02-01

    Full Text Available Abstract Background As the canonical code is not universal, different theories about its origin and organization have appeared. The optimization or level of adaptation of the canonical genetic code was measured taking into account the harmful consequences resulting from point mutations leading to the replacement of one amino acid for another. There are two basic theories to measure the level of optimization: the statistical approach, which compares the canonical genetic code with many randomly generated alternative ones, and the engineering approach, which compares the canonical code with the best possible alternative. Results Here we used a genetic algorithm to search for better adapted hypothetical codes and as a method to guess the difficulty in finding such alternative codes, allowing to clearly situate the canonical code in the fitness landscape. This novel proposal of the use of evolutionary computing provides a new perspective in the open debate between the use of the statistical approach, which postulates that the genetic code conserves amino acid properties far better than expected from a random code, and the engineering approach, which tends to indicate that the canonical genetic code is still far from optimal. We used two models of hypothetical codes: one that reflects the known examples of codon reassignment and the model most used in the two approaches which reflects the current genetic code translation table. Although the standard code is far from a possible optimum considering both models, when the more realistic model of the codon reassignments was used, the evolutionary algorithm had more difficulty to overcome the efficiency of the canonical genetic code. Conclusions Simulated evolution clearly reveals that the canonical genetic code is far from optimal regarding its optimization. Nevertheless, the efficiency of the canonical code increases when mistranslations are taken into account with the two models, as indicated by the

  12. Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

    Directory of Open Access Journals (Sweden)

    Lluís Aragonès

    2010-03-01

    Full Text Available Hepatitis A virus (HAV, the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

  13. Codon utilization, DNA landscaping and fractal analysis in bacteriophage phi(adh).

    Science.gov (United States)

    McEwan, N R

    2005-01-01

    The bacteriophage phi(adh) has a low G+C content and encodes its protein products using a restricted number of the codons, which it could theoretically use. Investigated were (i) the restricted codon usage by determining codon indices and codon distances for various genes and ORFs, (ii) distribution of purines and pyrimidines on the two strands of the double-stranded genome and within all genes and ORFs, and (iii) nucleotide positional bias within the genome. The genes and ORFs can be clustered into four groups, based on codon distance analysis. The genome landscape showed that the plus strand was more purine-rich than the negative one and that the only area of the genome where the landscape was located in the pyrimidine-rich region was at the start of the sequence which was also the only region of the genome where ORFs were found on the negative strand. The nucleotide composition of the genome, examined by fractal analysis showed little, if any, DNA positional bias, as opposed to overall compositional bias with a self-similarity profile. The ORFs showed a bias in favour of purines on the coding strand.

  14. Diversification rates indicate an early role of adaptive radiations at the origin of modern echinoid fauna.

    Directory of Open Access Journals (Sweden)

    Simon Boivin

    Full Text Available Evolutionary radiations are fascinating phenomena corresponding to a dramatic diversification of taxa and a burst of cladogenesis over short periods of time. Most evolutionary radiations have long been regarded as adaptive but this has seldom been demonstrated with large-scale comparative datasets including fossil data. Originating in the Early Jurassic, irregular echinoids are emblematic of the spectacular diversification of mobile marine faunas during the Mesozoic Marine Revolution. They diversified as they colonized various habitats, and now constitute the main component of echinoid fauna in modern seas. The evolutionary radiation of irregular echinoids has long been considered as adaptive but this hypothesis has never been tested. In the present work we analyze the evolution of echinoid species richness and morphological disparity over 37 million years based on an extensive fossil dataset. Our results demonstrate that morphological and functional diversifications in certain clades of irregular echinoids were exceptionally high compared to other clades and that they were associated with the evolution of new modes of life and so can be defined as adaptive radiations. The role played by ecological opportunities in the diversification of these clades was critical, with the evolution of the infaunal mode of life promoting the adaptive radiation of irregular echinoids.

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

    Science.gov (United States)

    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

  16. A common periodic table of codons and amino acids.

    Science.gov (United States)

    Biro, J C; Benyó, B; Sansom, C; Szlávecz, A; Fördös, G; Micsik, T; Benyó, Z

    2003-06-27

    A periodic table of codons has been designed where the codons are in regular locations. The table has four fields (16 places in each) one with each of the four nucleotides (A, U, G, C) in the central codon position. Thus, AAA (lysine), UUU (phenylalanine), GGG (glycine), and CCC (proline) were placed into the corners of the fields as the main codons (and amino acids) of the fields. They were connected to each other by six axes. The resulting nucleic acid periodic table showed perfect axial symmetry for codons. The corresponding amino acid table also displaced periodicity regarding the biochemical properties (charge and hydropathy) of the 20 amino acids and the position of the stop signals. The table emphasizes the importance of the central nucleotide in the codons and predicts that purines control the charge while pyrimidines determine the polarity of the amino acids. This prediction was experimentally tested.

  17. Codon usage and amino acid usage influence genes expression level.

    Science.gov (United States)

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

    2018-02-01

    Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

  18. Why has nature invented three stop codons of DNA and only one start codon?

    Czech Academy of Sciences Publication Activity Database

    Křížek, Michal; Křížek, P.

    2012-01-01

    Roč. 304, Jul 7 (2012), s. 183-187 ISSN 0022-5193 R&D Projects: GA AV ČR(CZ) IAA100190803 Institutional support: RVO:67985840 Keywords : DNA * RNA * stop codon * synchronization shift * drosophila genome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.351, year: 2012 http://www.sciencedirect.com/science/article/pii/S0022519312001580

  19. RESEARCH ARTICLE Codon usage vis-a-vis start and stop codon ...

    Indian Academy of Sciences (India)

    Prosen

    genetic code is not used in its built-in redundancy in the same way by all the species from prokaryotes ... Previous reports on codon bias study suggest that it is a complex process associated with several factors like ... Methods: The data used in the present study included the coding sequences from three dicot genomes i.e.,.

  20. Codon Deviation Coefficient: A novel measure for estimating codon usage bias and its statistical significance

    KAUST Repository

    Zhang, Zhang

    2012-03-22

    Background: Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.Results: Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.Conclusions: As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions. 2012 Zhang et al; licensee BioMed Central Ltd.

  1. Self-catalytic DNA depurination underlies human β-globin gene mutations at codon 6 that cause anemias and thalassemias.

    Science.gov (United States)

    Alvarez-Dominguez, Juan R; Amosova, Olga; Fresco, Jacques R

    2013-04-19

    The human β-globin gene contains an 18-nucleotide coding strand sequence centered at codon 6 and capable of forming a stem-loop structure that can self-catalyze depurination of the 5'G residue of that codon. The resultant apurinic lesion is subject to error-prone repair, consistent with the occurrence about this codon of mutations responsible for 6 anemias and β-thalassemias and additional substitutions without clinical consequences. The 4-residue loop of this stem-loop-forming sequence shows the highest incidence of mutation across the gene. The loop and first stem base pair-forming residues appeared early in the mammalian clade. The other stem-forming segments evolved more recently among primates, thereby conferring self-depurination capacity at codon 6. These observations indicate a conserved molecular mechanism leading to β-globin variants underlying phenotypic diversity and disease.

  2. Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage

    DEFF Research Database (Denmark)

    Yang, Ziheng; Nielsen, Rasmus

    2008-01-01

    to examine the null hypothesis that codon usage is due to mutation bias alone, not influenced by natural selection. Application of the test to the mammalian data led to rejection of the null hypothesis in most genes, suggesting that natural selection may be a driving force in the evolution of synonymous......Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we...... implement a few population genetics models of codon substitution that explicitly consider mutation bias and natural selection at the DNA level. Selection on codon usage is modeled by introducing codon-fitness parameters, which together with mutation-bias parameters, predict optimal codon frequencies...

  3. Genome-wide codon usage profiling of ocular infective Chlamydia trachomatis serovars and drug target identification.

    Science.gov (United States)

    Sadhasivam, Anupriya; Vetrivel, Umashankar

    2017-07-04

    Chlamydia trachomatis (C.t) is a Gram-negative obligate intracellular bacteria and is a major causative of infectious blindness and sexually transmitted diseases. Among the varied serovars of this organism, A, B and C are reported as prominent ocular pathogens. Genomic studies of these strains shall aid in deciphering potential drug targets and genomic influence on pathogenesis. Hence, in this study we performed deep statistical profiling of codon usage in these serovars. The overall base composition analysis reveals that these serovars are over biased to AU than GC. Similarly, relative synonymous codon usage also showed preference towards A/U ending codons. Parity Rule 2 analysis inferred unequal distribution of AT and GC, indicative of other unknown factors acting along with mutational pressure to influence codon usage bias (CUB). Moreover, absolute quantification of CUB also revealed lower bias across these serovars. The effect of natural selection on CUB was also confirmed by neutrality plot, reinforcing natural selection under mutational pressure turned to be a pivotal role in shaping the CUB in the strains studied. Correspondence analysis (COA) clarified that, C.t C/TW-3 to show a unique trend in codon usage variation. Host influence analysis on shaping the codon usage pattern also inferred some speculative relativity. In a nutshell, our finding suggests that mutational pressure is the dominating factor in shaping CUB in the strains studied, followed by natural selection. We also propose potential drug targets based on cumulative analysis of strand bias, CUB and human non-homologue screening.

  4. Assessment of students’ health condition by indicators of adaptation potential, biological age and bio-energetic reserves of organism

    Directory of Open Access Journals (Sweden)

    O.V. Martyniuk

    2015-06-01

    Full Text Available Purpose: to assess students’ health condition by indicators of adaptation potential, biological age and express-assessment. Material: in the research 47 first and second year girl students participated, who belonged to main health group. Results: we distributed the girl students into three groups: 14.89% of them were included in group with “safe” health condition; 34.04% - in group of “third state”; 51.06% were related to group with “ dangerous” health condition. We established that dangerous level was characterized by energy potential of below middle and low level. It is accompanied by accelerated processes of organism’s age destructions and tension of regulation mechanisms. Conclusions: the received results permit to further develop and generalize the data of students’ health’s assessment by indicators of adaptation potentials, biological age and physical health’s condition.

  5. Gender-specific selection on codon usage in plant genomes

    Directory of Open Access Journals (Sweden)

    Krochko Joan E

    2007-06-01

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

  6. Analysis of codon usage and nucleotide composition bias in polioviruses

    Directory of Open Access Journals (Sweden)

    Gu Yuan-xing

    2011-03-01

    Full Text Available Abstract Background Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date. Methods The relative synonymous codon usage (RSCU values, effective number of codon (ENC values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3. Results The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses. No significant effect in gene length or vaccine derived polioviruses (DVPVs, wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1. Conclusion The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.

  7. Adaptation.

    Science.gov (United States)

    Broom, Donald M

    2006-01-01

    The term adaptation is used in biology in three different ways. It may refer to changes which occur at the cell and organ level, or at the individual level, or at the level of gene action and evolutionary processes. Adaptation by cells, especially nerve cells helps in: communication within the body, the distinguishing of stimuli, the avoidance of overload and the conservation of energy. The time course and complexity of these mechanisms varies. Adaptive characters of organisms, including adaptive behaviours, increase fitness so this adaptation is evolutionary. The major part of this paper concerns adaptation by individuals and its relationships to welfare. In complex animals, feed forward control is widely used. Individuals predict problems and adapt by acting before the environmental effect is substantial. Much of adaptation involves brain control and animals have a set of needs, located in the brain and acting largely via motivational mechanisms, to regulate life. Needs may be for resources but are also for actions and stimuli which are part of the mechanism which has evolved to obtain the resources. Hence pigs do not just need food but need to be able to carry out actions like rooting in earth or manipulating materials which are part of foraging behaviour. The welfare of an individual is its state as regards its attempts to cope with its environment. This state includes various adaptive mechanisms including feelings and those which cope with disease. The part of welfare which is concerned with coping with pathology is health. Disease, which implies some significant effect of pathology, always results in poor welfare. Welfare varies over a range from very good, when adaptation is effective and there are feelings of pleasure or contentment, to very poor. A key point concerning the concept of individual adaptation in relation to welfare is that welfare may be good or poor while adaptation is occurring. Some adaptation is very easy and energetically cheap and

  8. Behaviour of reindeer as an indicator of an adaptation to feeding

    Directory of Open Access Journals (Sweden)

    Anna Nilsson

    2004-04-01

    Full Text Available Abstract: We assessed behaviour of reindeer affected by nutritional deprivation and how they adapted to various feeding strategies. The activity pattern of 61 penned eight month old female reindeer calves was observed during 20 of a total of 42 experimental days in winter 1997. The dominant activities were lying, ruminating, intake of feed and water, and standing. Few recordings of agonistic behaviour or snow intake occured. Restricted feed intake, half the ad lib. ration of a lichen-based diet, affected the eating behaviour of the reindeer, and more animals were standing and fewer lying compared to reindeer fed ad lib. Lack of energy in the diet correlated with animals lying curled up (lying with the muzzle close to the hind legs. This behaviour could be a useful complement to other measurements and registrations when studying adaptations to various feeding regimens.Abstract in Swedish/Sammanfattning:Syftet med studien var att undersöka om, och i så fall hur renars beteende påverkades av otillräckligt näringsintag och vid anpassning till olika utfodringsstrategier. Aktivitetsmönstret hos 61 inhägnade åtta månader gamla honrenkalvar studerades under 20 av totalt 42 försöksdagar. De vanligaste beteendekategorierna genom hela försöket var ligga, idissla, intag av foder och vatten samt stå passivt. Endast ett fåtal observationer av aggressivt beteende och snöätande registrerades. En begränsad giva dvs. halva mängden av fodergivan vid fri tillgång av en lavbaserad diet påverkade djuren ätbeteende. Dessutom observerades fler djur stå passivt medan färre låg jämfört med kontrollgruppen. Under första fasen av utfodring efter restriktionsperioden låg fler djur låg ihoprullade (med mulen tätt intill bakbenet jämfört med kontrollgruppen, vilket tolkades som ett tecken på energibrist. Beteendestudierna visade sig vara ett värdefullt komplement till övriga mätningar och provtagningar vid studier av renars anpassning till

  9. Adapting the European tourism indicators system to Braşov – tourist destination

    Directory of Open Access Journals (Sweden)

    Gabriel BRĂTUCU

    2015-12-01

    Full Text Available The industry of tourism contributes mainly to the social and economic development of a destination. However this development has to be made in a sustainable manner, with an emphasis on preserving the area where it is practiced. In order to evaluate the sustainable development of a destination, the European Commission developed an Indicators System that measures and monitors, at a local level, the processes of sustainable development and communicates to the interested parties its progress and its future performances. Therefore, the aim of this paper is to identify the set of indicators from European Tourism Indicators System that are relevant in evaluating the sustainable development of tourism in Braşov. In order to achieve this objective 3 focus Groups were conducted among 30 specialists in this field. The results can serve as a guid

  10. Research on professional adaptability psychological selection indices of nuclear power plant operators

    International Nuclear Information System (INIS)

    Liu Jingquan; Li Zhe; Li Maoyou

    2010-01-01

    Based on the analysis of the work characteristics of nuclear power plant operators and the comparison of professional psychological selection indices for different occupations, the indices of psychological selection system which is applicable to nuclear power plant operators are proposed in this paper, using the method named 'taking classes,cross-comparison'. The index results of the suggested psychological selection system reflects all the professional requirements on the nuclear power plant operators, which can also be used for the recruitment, training and the retraining programs for operators. (authors)

  11. Nucleotide composition bias and codon usage trends of gene ...

    Indian Academy of Sciences (India)

    2015-06-10

    Jun 10, 2015 ... Figure 1. Variations of the nucleotide composition of genes of the two mycoplasma species. (a) M. capricolum subsp. capricolum;. (b) M. agalactiae. Journal of Genetics, Vol. 94, No. 2, June 2015 ..... 2010 Codon usage bias and the evolution of influenza A viruses. Codon usage biases of influenza virus.

  12. Genomic composition factors affect codon usage in porcine genome ...

    African Journals Online (AJOL)

    The objective of the study was to determine the codon usage bias in the porcine genome and decipher its determinants. To investigate the underlying mechanisms of codon bias, the coding sequence (CDS) from the swine reference sequence (ssc10.2) was extracted using Biomart. An in house built Perl script was used to ...

  13. Comparative studies on codon usage pattern of chloroplasts and ...

    Indian Academy of Sciences (India)

    A detailed comparison was made of codon usage of chloroplast genes with their host (nuclear) genes in the four angiosperm species Oryza sativa, Zea mays, Triticum aestivum and Arabidopsis thaliana. The average GC content of the entire genes, and at the three codon positions individually, was higher in nuclear than in ...

  14. The relationship between codon usage bias and cold resistant genes

    International Nuclear Information System (INIS)

    Barozai, M.Y.; Din, M.

    2014-01-01

    This research is based on synonymous codon usage which has been well-known as a feature that affects typical expression level of protein in an organism. Different organisms prefer different codons for same amino acid and this is called Codon Usage Bias (CUB). The codon usage directly affects the level or even direction of changes in protein expression in responses to environmental stimuli. Cold stress is a major abiotic factor that limits the agricultural productivity of plants. In the recent study CUB has been studied in Arabidopsis thaliana cold resistant and housekeeping genes and their homologs in rice (Oryza sativa) to understand the cold stress and housekeeping genes relation with CUB. Six cold resistant and three housekeeping genes in Arabidopsis thaliana and their homologs in rice, were subjected to CUB analysis. The three cold resistant genes (DREB1B, RCI and MYB15) showed more than 50% (52%, 61% and 66% respectively) similar codon usage bias for Arabidopsis thaliana and rice. On the other hand three cold resistant genes (MPK3, ICE1 and ZAT12) showed less than 50% (38%, 38% and 47% respectively) similar codon usage bias for Arabidopsis thaliana and rice. The three housekeeping genes (Actin, Tubulin and Ubiquitin) showed 76% similar codon usage bias for Arabidopsis thaliana and rice. This study will help to manage the plant gene expression through codon optimization under the cold stress. (author)

  15. Comparative analysis of codon usage bias in Crenarchaea and ...

    Indian Academy of Sciences (India)

    executed to understand the pattern of codon usage bias between the high expression genes (HEG) and the whole genomes in two Archaeal phyla, Crenarchaea ... technologies have widened the scope of microbiology in the recent years. .... comprehend the varied evolution of G/C or A/T richness of codons used in the HEG ...

  16. Nucleotide composition bias and codon usage trends of gene ...

    Indian Academy of Sciences (India)

    Table 2. Comparative synonymous codon usage patterns of the two mycoplasmas and ovine genomes. Codon (amino acid). Ovine*. M. capricolum .... Supplementary data, J. Genet. 94, 251–260. Table 4. Nucleotide composition statistics for a gene population in the two mycoplasma species. f ′. 1 = 6.75%# f ′. 2 = 5.82% ...

  17. Synonymous codon usage in different protein secondary structural ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    2007-06-21

    Jun 21, 2007 ... usage of Lactobacillus species; Nucleic Acids Res. 22. 929–936. Siemion I Z and Siemion P J 1994 The informational context of the third base in amino acid codons; Biosystems 33. 139–148. Tao X and Dafu D 1998 The relationship between synonymous codon usage and protein Structure; FEBS Lett.

  18. Extended model of raw data signals for space-time adaptive processing and moving target indicators

    NARCIS (Netherlands)

    Lidický, L.; Hoogeboom, P.

    2006-01-01

    This paper presents a multi-channel synthetic aperture radar (SAR) signal model. Its purpose is to study nonstationary raw SAR signals in moving target indication (MTI) systems. This is opposed to the traditional approach in which only stationary (harmonic) signals are considered. The principal

  19. Codon usage bias in animals: disentangling the effects of natural selection, effective population size and GC-biased gene conversion.

    Science.gov (United States)

    Galtier, N; Roux, C; Rousselle, M; Romiguier, J; Figuet, E; Glémin, S; Bierne, N; Duret, L

    2018-01-30

    Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, non-adaptive processes such as GC-biased gene conversion and experimental artefacts. Using population transcriptomics data we analysed the relationship between codon usage, gene expression, allele frequency distribution and recombination rate in 30 non-model species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased gene conversion on codon usage by separately analysing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased gene conversion, which is widespread in animals and the main force determining the fate of AT↔GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne. © The Author 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Codon-Precise, Synthetic, Antibody Fragment Libraries Built Using Automated Hexamer Codon Additions and Validated through Next Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Laura Frigotto

    2015-05-01

    Full Text Available We have previously described ProxiMAX, a technology that enables the fabrication of precise, combinatorial gene libraries via codon-by-codon saturation mutagenesis. ProxiMAX was originally performed using manual, enzymatic transfer of codons via blunt-end ligation. Here we present Colibra™: an automated, proprietary version of ProxiMAX used specifically for antibody library generation, in which double-codon hexamers are transferred during the saturation cycling process. The reduction in process complexity, resulting library quality and an unprecedented saturation of up to 24 contiguous codons are described. Utility of the method is demonstrated via fabrication of complementarity determining regions (CDR in antibody fragment libraries and next generation sequencing (NGS analysis of their quality and diversity.

  1. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    . Dar es Salaam. Durban. Bloemfontein. Antananarivo. Cape Town. Ifrane ... program strategy. A number of CCAA-supported projects have relevance to other important adaptation-related themes such as disaster preparedness and climate.

  2. Forces that influence the evolution of codon bias

    Science.gov (United States)

    Sharp, Paul M.; Emery, Laura R.; Zeng, Kai

    2010-01-01

    The frequencies of alternative synonymous codons vary both among species and among genes from the same genome. These patterns have been inferred to reflect the action of natural selection. Here we evaluate this in bacteria. While intragenomic variation in many species is consistent with selection favouring translationally optimal codons, much of the variation among species appears to be due to biased patterns of mutation. The strength of selection on codon usage can be estimated by two different approaches. First, the extent of bias in favour of translationally optimal codons in highly expressed genes, compared to that in genes where selection is weak, reveals the long-term effectiveness of selection. Here we show that the strength of selected codon usage bias is highly correlated with bacterial growth rate, suggesting that selection has favoured translational efficiency. Second, the pattern of bias towards optimal codons at polymorphic sites reveals the ongoing action of selection. Using this approach we obtained results that were completely consistent with the first method; importantly, the frequency spectra of optimal codons at polymorphic sites were similar to those predicted under an equilibrium model. Highly expressed genes in Escherichia coli appear to be under continuing strong selection, whereas selection is very weak in genes expressed at low levels. PMID:20308095

  3. fMR-adaptation indicates selectivity to audiovisual content congruency in distributed clusters in human superior temporal cortex

    Directory of Open Access Journals (Sweden)

    Blomert Leo

    2010-02-01

    Full Text Available Abstract Background Efficient multisensory integration is of vital importance for adequate interaction with the environment. In addition to basic binding cues like temporal and spatial coherence, meaningful multisensory information is also bound together by content-based associations. Many functional Magnetic Resonance Imaging (fMRI studies propose the (posterior superior temporal cortex (STC as the key structure for integrating meaningful multisensory information. However, a still unanswered question is how superior temporal cortex encodes content-based associations, especially in light of inconsistent results from studies comparing brain activation to semantically matching (congruent versus nonmatching (incongruent multisensory inputs. Here, we used fMR-adaptation (fMR-A in order to circumvent potential problems with standard fMRI approaches, including spatial averaging and amplitude saturation confounds. We presented repetitions of audiovisual stimuli (letter-speech sound pairs and manipulated the associative relation between the auditory and visual inputs (congruent/incongruent pairs. We predicted that if multisensory neuronal populations exist in STC and encode audiovisual content relatedness, adaptation should be affected by the manipulated audiovisual relation. Results The results revealed an occipital-temporal network that adapted independently of the audiovisual relation. Interestingly, several smaller clusters distributed over superior temporal cortex within that network, adapted stronger to congruent than to incongruent audiovisual repetitions, indicating sensitivity to content congruency. Conclusions These results suggest that the revealed clusters contain multisensory neuronal populations that encode content relatedness by selectively responding to congruent audiovisual inputs, since unisensory neuronal populations are assumed to be insensitive to the audiovisual relation. These findings extend our previously revealed mechanism for

  4. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  5. Influenza A Virus Attenuation by Codon Deoptimization of the NS Gene for Vaccine Development

    Science.gov (United States)

    Nogales, Aitor; Baker, Steven F.; Ortiz-Riaño, Emilio; Dewhurst, Stephen; Topham, David J.

    2014-01-01

    ABSTRACT Influenza viral infection represents a serious public health problem that causes contagious respiratory disease, which is most effectively prevented through vaccination to reduce transmission and future infection. The nonstructural (NS) gene of influenza A virus encodes an mRNA transcript that is alternatively spliced to express two viral proteins, the nonstructural protein 1 (NS1) and the nuclear export protein (NEP). The importance of the NS gene of influenza A virus for viral replication and virulence has been well described and represents an attractive target to generate live attenuated influenza viruses with vaccine potential. Considering that most amino acids can be synthesized from several synonymous codons, this study employed the use of misrepresented mammalian codons (codon deoptimization) for the de novo synthesis of a viral NS RNA segment based on influenza A/Puerto Rico/8/1934 (H1N1) (PR8) virus. We generated three different recombinant influenza PR8 viruses containing codon-deoptimized synonymous mutations in coding regions comprising the entire NS gene or the mRNA corresponding to the individual viral protein NS1 or NEP, without modifying the respective splicing and packaging signals of the viral segment. The fitness of these synthetic viruses was attenuated in vivo, while they retained immunogenicity, conferring both homologous and heterologous protection against influenza A virus challenges. These results indicate that influenza viruses can be effectively attenuated by synonymous codon deoptimization of the NS gene and open the possibility of their use as a safe vaccine to prevent infections with these important human pathogens. IMPORTANCE Vaccination serves as the best therapeutic option to protect humans against influenza viral infections. However, the efficacy of current influenza vaccines is suboptimal, and novel approaches are necessary for the prevention of disease cause by this important human respiratory pathogen. The nonstructural

  6. Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

    Science.gov (United States)

    Kegler-Ebo, D M; Docktor, C M; DiMaio, D

    1994-05-11

    We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequences for the restriction endonuclease Sapl, an enzyme that cleaves outside of its recognition sequence. The intermediate molecule containing the mutagenic cassette is then digested with Sapl, thereby removing most of the mutagenic cassette, leaving only a three base cohesive overhang that is ligated to generate the final insertion or substitution mutation. A general method for constructing blunt-end target molecules suitable for this approach is also described. Because the mutagenic cassette is excised during this procedure and alters the target only by introducing the desired mutation, the same cassette can be used to introduce a particular codon at all target sites. Each cassette can deposit two different codons, depending on the orientation in which it is inserted into the target molecule. Therefore, a series of eleven cassettes is sufficient to insert all possible amino acids at any constructed target site. Thus codon cassettes are 'off-the-shelf' reagents, and this methodology should be a particularly useful and inexpensive approach for subjecting multiple different positions in a protein sequence to saturation mutagenesis.

  7. Emergent Rules for Codon Choice Elucidated by Editing Rare Arginine Codons in Escherichia coli

    Science.gov (United States)

    2016-09-20

    75272 Paris, France; fProgram in Chemical Biology, Harvard University, Cambridge, MA 02138; gNational University of Singapore, School of Computing ...from its essential genes (see Fig. 1A and Dataset S1 for a complete list of AGR codons in essential genes). CoS-MAGE leverages Lambda Red-mediated...pre- viously optimized for efficient Lambda Red-mediated genome engineering (33, 36). Using CoS-MAGE on EcM2.1 improves allele replacement frequency by

  8. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    Nairobi, Kenya. 28 Adapting Fishing Policy to Climate Change with the Aid of Scientific and Endogenous Knowledge. Cap Verde, Gambia,. Guinea, Guinea Bissau,. Mauritania and Senegal. Environment and Development in the Third World. (ENDA-TM). Dakar, Senegal. 29 Integrating Indigenous Knowledge in Climate Risk ...

  9. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails.

    Science.gov (United States)

    Mu, Huawei; Sun, Jin; Cheung, Siu Gin; Fang, Ling; Zhou, Haiyun; Luan, Tiangang; Zhang, Huoming; Wong, Chris K C; Qiu, Jian-Wen

    2018-02-10

    Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL -1 ) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. Rapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic responses of two

  10. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei

    2017-11-06

    Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

  11. Genetic and codon usage bias analyses of polymerase genes of equine influenza virus and its relation to evolution.

    Science.gov (United States)

    Bera, Bidhan Ch; Virmani, Nitin; Kumar, Naveen; Anand, Taruna; Pavulraj, S; Rash, Adam; Elton, Debra; Rash, Nicola; Bhatia, Sandeep; Sood, Richa; Singh, Raj Kumar; Tripathi, Bhupendra Nath

    2017-08-23

    Equine influenza is a major health problem of equines worldwide. The polymerase genes of influenza virus have key roles in virus replication, transcription, transmission between hosts and pathogenesis. Hence, the comprehensive genetic and codon usage bias of polymerase genes of equine influenza virus (EIV) were analyzed to elucidate the genetic and evolutionary relationships in a novel perspective. The group - specific consensus amino acid substitutions were identified in all polymerase genes of EIVs that led to divergence of EIVs into various clades. The consistent amino acid changes were also detected in the Florida clade 2 EIVs circulating in Europe and Asia since 2007. To study the codon usage patterns, a total of 281,324 codons of polymerase genes of EIV H3N8 isolates from 1963 to 2015 were systemically analyzed. The polymerase genes of EIVs exhibit a weak codon usage bias. The ENc-GC3s and Neutrality plots indicated that natural selection is the major influencing factor of codon usage bias, and that the impact of mutation pressure is comparatively minor. The methods for estimating host imposed translation pressure suggested that the polymerase acidic (PA) gene seems to be under less translational pressure compared to polymerase basic 1 (PB1) and polymerase basic 2 (PB2) genes. The multivariate statistical analysis of polymerase genes divided EIVs into four evolutionary diverged clusters - Pre-divergent, Eurasian, Florida sub-lineage 1 and 2. Various lineage specific amino acid substitutions observed in all polymerase genes of EIVs and especially, clade 2 EIVs underwent major variations which led to the emergence of a phylogenetically distinct group of EIVs originating from Richmond/1/07. The codon usage bias was low in all the polymerase genes of EIVs that was influenced by the multiple factors such as the nucleotide compositions, mutation pressure, aromaticity and hydropathicity. However, natural selection was the major influencing factor in defining the

  12. Human alpha and beta papillomaviruses use different synonymous codon profiles.

    Science.gov (United States)

    Cladel, Nancy M; Bertotto, Alex; Christensen, Neil D

    2010-06-01

    Human papillomaviruses use rare codons relative to their hosts. It has been theorized that this is a mechanism to allow the virus to escape immune surveillance. In the present study, we examined the codings of four major genes of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic) viruses. We compared the codon usage of different genes from a given papillomavirus and also the same genes from different papillomaviruses. Our data showed that codon usage was not always uniform between two genes of a given papillomavirus or between the same genes of papillomaviruses from different genera. We speculate as to why this might be and conclude that codon usage in the papillomaviruses may not only play a role in facilitating escape from immune surveillance but may also underlie some of the unanswered questions in the papillomavirus field.

  13. Combination of the Endogenous lhcsr1 Promoter and Codon Usage Optimization Boosts Protein Expression in the Moss Physcomitrella patens

    Directory of Open Access Journals (Sweden)

    Manuel Hiss

    2017-10-01

    Full Text Available The moss Physcomitrella patens is used both as an evo-devo model and biotechnological production system for metabolites and pharmaceuticals. Strong in vivo expression of genes of interest is important for production of recombinant proteins, e.g., selectable markers, fluorescent proteins, or enzymes. In this regard, the choice of the promoter sequence as well as codon usage optimization are two important inside factors to consider in order to obtain optimum protein accumulation level. To reliably quantify fluorescence, we transfected protoplasts with promoter:GFP fusion constructs and measured fluorescence intensity of living protoplasts in a plate reader system. We used the red fluorescent protein mCherry under 2x 35S promoter control as second reporter to normalize for different transfection efficiencies. We derived a novel endogenous promoter and compared deletion variants with exogenous promoters. We used different codon-adapted green fluorescent protein (GFP genes to evaluate the influence of promoter choice and codon optimization on protein accumulation in P. patens, and show that the promoter of the gene of P. patens chlorophyll a/b binding protein lhcsr1 drives expression of GFP in protoplasts significantly (more than twofold better than the commonly used 2x 35S promoter or the rice actin1 promoter. We identified a shortened 677 bp version of the lhcsr1 promoter that retains full activity in protoplasts. The codon optimized GFP yields significantly (more than twofold stronger fluorescence signals and thus demonstrates that adjusting codon usage in P. patens can increase expression strength. In combination, new promotor and codon optimized GFP conveyed sixfold increased fluorescence signal.

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

    Directory of Open Access Journals (Sweden)

    Dinglin Zhang

    Full Text Available 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.

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

    Science.gov (United States)

    Zhang, Dinglin; Chen, Danfeng; 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.

  16. Endocrine response to realimentation in young northern elephant seals (Mirounga angustirostris): Indications for development of fasting adaptation.

    Science.gov (United States)

    Dailey, Rachael E; Fontaine, Christine M; Avery, Julie P

    2016-09-01

    Most organisms undergo changes in their environment, both predictably and unpredictably, which require them to alter priorities in nutrient allocation with regards to food availability. Species that more predictably encounter extended periods of limited food resources or intake while mitigating the negative effects of starvation are considered to be fasting adapted. Northern elephant seals (NES) are one such species and routinely undergo extended periods of fasting for breeding, molting, as well as a post-weaning fast at 6-8weeks of age. However, during unusual times of nutritional deprivation, animals may enter stage III fasting. While fasting and foraging in this species has been extensively studied, realimentation following fasting beyond normal life history parameters has not been investigated. In this study, changes in ghrelin, growth hormone (GH), and insulin-like growth factor (IGF)-I were compared across 8weeks of realimentation following emaciation in three age classes: neonates, post-molt pups, and yearlings. Longitudinal changes in hormone profiles indicate that neonate and post-molt pups are slow to recover mass and positive energy balance despite an energy dense diet fed at 10% body mass. In addition, ghrelin and GH concentrations remained elevated in post-molt pups compared to other age classes. Changes in hormone concentrations early in realimentation indicate that yearling animals recover more rapidly from periods of nutritional deprivation than do younger animals. Overall, this suggests that the ability to regulate metabolic homeostasis with regards to nutrient allocation may develop over time, even in a species that is considered to be fasting adapted. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Adaptation of the short intergenic spacers between co-directional genes to the Shine-Dalgarno motif among prokaryote genomes

    DEFF Research Database (Denmark)

    Caro, Albert Pallejà; García-Vallvé, Santiago; Romeu, Antoni

    2009-01-01

    , the stop codon usage of the upstream gene changes to accommodate the overlap between the SD sequence and the stop codon. CONCLUSION: The SD presence makes the intergenic lengths from 5 to 8 bps less frequent and causes an adaptation of the stop codon usage. Our results introduce new elements...

  18. Ribosomal readthrough at a short UGA stop codon context triggers dual localization of metabolic enzymes in Fungi and animals.

    Directory of Open Access Journals (Sweden)

    Alina C Stiebler

    2014-10-01

    Full Text Available Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. Here, we report that in human cells programmed stop codon readthrough is used to generate peroxisomal isoforms of cytosolic enzymes. We could show for NAD-dependent lactate dehydrogenase B (LDHB and NAD-dependent malate dehydrogenase 1 (MDH1 that translational readthrough results in C-terminally extended protein variants containing a peroxisomal targeting signal 1 (PTS1. Efficient readthrough occurs at a short sequence motif consisting of a UGA termination codon followed by the dinucleotide CU. Leaky termination at this stop codon context was observed in fungi and mammals. Comparative genome analysis allowed us to identify further readthrough-derived peroxisomal isoforms of metabolic enzymes in diverse model organisms. Overall, our study highlights that a defined stop codon context can trigger efficient ribosomal readthrough to generate dually targeted protein isoforms. We speculate that beyond peroxisomal targeting stop codon readthrough may have also other important biological functions, which remain to be elucidated.

  19. Evaluation of p53 codon 72 polymorphism in adenocarcinomas of the colon and rectum in La Plata, Argentina.

    Science.gov (United States)

    Pérez, Luis Orlando; Abba, Martin Carlos; Dulout, Fernando Noel; Golijow, Carlos Daniel

    2006-03-07

    To evaluate the potential association between p53 codon 72 polymorphism and sporadic colorectal adenocarcinoma development,and human papillomavirus (HPV) infection. One-hundred and nine controls and 53 patients with colon cancer from the city of La Plata, Argentina were analyzed. p53 codon 72 genotypes and HPV infection were identified using allele-specific polymerase chain reaction and nested polymerase chain reaction, respectively. The differences in the distribution of p53 codon 72 polymorphism between the cases and controls were statistically significant. The arginine allele had a prevalence of 0.65 in controls and 0.77 in cases. The corresponding odds ratio for the homozygous arginine genotype was 2.08 (95% CI, 1.06-4.05; P<0.05). Lack of association was found between p53 polymorphism and HPV infection in the set of adenocarcinomas. The findings of the present study indicate that p53 codon 72 arginine homozygous genotype may represent a genetic predisposing factor for colon cancer development. However,further studies are needed in order to elucidate the role of p53 codon 72 polymorphism in colorectal cancer.

  20. [Assessing work-related stress: an Italian adaptation of the HSE Management Standards Work-Related Stress Indicator Tool].

    Science.gov (United States)

    Marcatto, Francesco; D'Errico, Giuseppe; Di Blas, Lisa; Ferrante, Donatella

    2011-01-01

    The aim of this paper is to present a preliminary validation of an Italian adaptation of the HSE Management Standards Work-Related Stress Indicator Tool (IT), an instrument for assessing work-related stress at the organizational level, originally developed in Britain by the Health and Safety Executive. A scale that assesses the physical work environment has been added to the original version of the IT. 190 employees of the University of Trieste have been enrolled in the study. A confirmatory analysis showed a satisfactory fit of the eight-factors structure of the instrument. Further psychometric analysis showed adequate internal consistency of the IT scales and good criterion validity, as evidenced by the correlations with self-perception of stress, work satisfaction and motivation. In conclusion, the Indicator Tool proved to be a valid and reliable instrument for the assessment of work-related stress at the organizational level, and it is also compatible with the instructions provided by the Ministry of Labour and Social Policy (Circular letter 18/11/2010).

  1. Metabolite profiles of nodulated alfalfa plants indicate that distinct stages of nodule organogenesis are accompanied by global physiological adaptations.

    Science.gov (United States)

    Barsch, Aiko; Tellström, Verena; Patschkowski, Thomas; Küster, Helge; Niehaus, Karsten

    2006-09-01

    An effective symbiosis between Sinorhizobium meliloti and its host plant Medicago sativa is dependent on a balanced physiological interaction enabling the microsymbiont to fix atmospheric nitrogen. Maintenance of the symbiotic interaction is regulated by still poorly understood control mechanisms. A first step toward a better understanding of nodule metabolism was the determination of characteristic metabolites for alfalfa root nodules. Furthermore, nodules arrested at different developmental stages were analyzed in order to address metabolic changes induced during the progression of nodule formation. Metabolite profiles of bacteroid-free pseudonodule extracts indicated that early nodule developmental processes are accompanied by photosynthate translocation but no massive organic acid formation. To determine metabolic adaptations induced by the presence of nonfixing bacteroids, nodules induced by mutant S. meliloti strains lacking the nitrogenase protein were analyzed. The bacteroids are unable to provide ammonium to the host plant, which is metabolically reflected by reduced levels of characteristic amino acids involved in ammonium fixation. Elevated levels of starch and sugars in Fix(-) nodules provide strong evidence that plant sanctions preventing a transformation from a symbiotic to a potentially parasitic interaction are not strictly realized via photosynthate supply. Instead, metabolic and gene expression data indicate that alfalfa plants react to nitrogen-fixation-deficient bacteroids with a decreased organic acid synthesis and an early induction of senescence. Noneffective symbiotic interactions resulting from plants nodulated by mutant rhizobia also are reflected in characteristic metabolic changes in leaves. These are typical for nitrogen deficiency, but also highlight metabolites potentially involved in sensing the N status.

  2. Long-term study of Sarcoptes scabiei infection in Norwegian red foxes (Vulpes vulpes) indicating host/parasite adaptation.

    Science.gov (United States)

    Davidson, Rebecca K; Bornstein, Set; Handeland, Kjell

    2008-10-01

    The red fox (Vulpes vulpes) population, in Norway, was naïve to Sarcoptes scabiei prior to the late 1970s when this parasite was first recorded and a still ongoing epidemic started. During the course of this protracted epidemic some degree of host/parasite adaptation, with the occurrence of healthy antibody positive foxes, might be expected. In the present study the prevalence of sarcoptic mange and serologically identified S. scabiei exposure was investigated in 363 Norwegian red foxes, shot by hunters during two different study periods (1994-1995 and 2002-2005). The sarcoptic mange diagnosis was based upon the presence of clearly visible lesions in the skin of the cadaver with confirmatory demonstration of S. scabiei. The serodiagnosis was based on an indirect-ELISA. There was a significant decrease in prevalence of both mange cases and seropositive animals from the first to the second study period. Whilst the mange prevalence fell more than threefold, from 30.0% to 6.6%, the seroprevalence dropped less dramatically from 53.3% to 19.1%. The smaller decrease in seroprevalence compared to mange cases reflected a significantly higher ratio of seropositive-mange negative versus seropositive-mange positive foxes, during the second study period, 40:18, compared to the first, 14:18. These findings indicate that the red fox population is adapting to live with the parasite and that low-grade or sub-clinical infections, and even recoveries, occur amongst exposed foxes. Mange positive foxes had significantly poorer body condition than those without sarcoptic mange. No significant difference in body condition was seen between seropositive-mange negative versus seronegative-mange negative foxes. The ELISA sensitivity was found to be 95% and proved a useful tool for investigating the exposure to S. scabiei in wild foxes. This study is believed to be the first pointing to a long-term Sarcoptes/fox adaptation, combining long-term prevalence studies of clinical sarcoptic mange

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

    Directory of Open Access Journals (Sweden)

    Xiuzhang Li

    2016-07-01

    Full Text Available 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.

  4. Role of Hp system in adaptation of specific immunity indices to the influence of moderate physical activity

    Directory of Open Access Journals (Sweden)

    V. L. Sokolenko

    2014-04-01

    Full Text Available The aim of this study is to determine the role of haptoglobin phenotype in realization of adaptive responses of cellular and humoral immunity indices to moderate exercise caused by physical training. The study was implemented in the group of second-year students aged 18–20 who lived in the same climatic and geographical conditions for a long period of time. The students didn’t have any acute or chronic diseases and attended the main group of physical training. 60 persons were investigated. Immune system indices analysis was carried out in September before and after physical training lessons. Leukocyte level was calculated using hemocytometer, lymphocyte level was determined on the base of blood smear (dyeing for Romanowsky–Giemsa. Expression of surface antigene by peripheral blood lymphocyte was determined by immuno-fluorescence method with the use of monoclonal antibodies. The level of immunoglobulin in plasma was determined by radial immunodiffusion or Mancini method. To assess the phenotype of haptoglobin (Hp we used the method of electrophoresis in starch gels. In the course of research we have detected the reduction of the relative and total number of lymphocytes regardless of haptoglobin phenotype in the group of students after physical training; this is a typical feature of the initial stages of stress response. We observed statistically reliable decrease in total number of analyzed subpopulations of T-lymphocyte in the group of students with phenotype Hp2-2 which was obviously the result of changes in the general level of lymphocytes in the peripheral blood. In the group of students with phenotype Hp1-1 absolute number of T-lymphocyte with phenotype CD3+ and CD4+ is reduced. In the group of students with phenotype Hp2-1 we have seen only the tendency to decrease in functional mature T-lymphocyte and their helper subpopulation. In the group of students with phenotype Hp2-2 the relative number of helper T-lymphocyte with the

  5. Streptomycin interferes with conformational coupling between codon recognition and GTPase activation on the ribosome.

    Science.gov (United States)

    Gromadski, Kirill B; Rodnina, Marina V

    2004-04-01

    Aminoacyl-tRNAs (aa-tRNAs) are selected by the ribosome through a kinetically controlled induced fit mechanism. Cognate codon recognition induces a conformational change in the decoding center and a domain closure of the 30S subunit. We studied how these global structural rearrangements are related to tRNA discrimination by using streptomycin to restrict the conformational flexibility of the 30S subunit. The antibiotic stabilized aa-tRNA on the ribosome both with a cognate and with a near-cognate codon in the A site. Streptomycin altered the rates of GTP hydrolysis by elongation factor Tu (EF-Tu) on cognate and near-cognate codons, resulting in almost identical rates of GTP hydrolysis and virtually complete loss of selectivity. These results indicate that movements within the 30S subunit at the streptomycin-binding site are essential for the coupling between base pair recognition and GTP hydrolysis, thus modulating the fidelity of aa-tRNA selection.

  6. The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria.

    Science.gov (United States)

    Li, Gene-Wei; Oh, Eugene; Weissman, Jonathan S

    2012-03-28

    Protein synthesis by ribosomes takes place on a linear substrate but at non-uniform speeds. Transient pausing of ribosomes can affect a variety of co-translational processes, including protein targeting and folding. These pauses are influenced by the sequence of the messenger RNA. Thus, redundancy in the genetic code allows the same protein to be translated at different rates. However, our knowledge of both the position and the mechanism of translational pausing in vivo is highly limited. Here we present a genome-wide analysis of translational pausing in bacteria by ribosome profiling--deep sequencing of ribosome-protected mRNA fragments. This approach enables the high-resolution measurement of ribosome density profiles along most transcripts at unperturbed, endogenous expression levels. Unexpectedly, we found that codons decoded by rare transfer RNAs do not lead to slow translation under nutrient-rich conditions. Instead, Shine-Dalgarno-(SD)-like features within coding sequences cause pervasive translational pausing. Using an orthogonal ribosome possessing an altered anti-SD sequence, we show that pausing is due to hybridization between the mRNA and 16S ribosomal RNA of the translating ribosome. In protein-coding sequences, internal SD sequences are disfavoured, which leads to biased usage, avoiding codons and codon pairs that resemble canonical SD sites. Our results indicate that internal SD-like sequences are a major determinant of translation rates and a global driving force for the coding of bacterial genomes.

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

    Science.gov (United States)

    Dohra, Hideo; Fujishima, Masahiro; Suzuki, Haruo

    2015-10-07

    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. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Codon usage bias and its influencing factors for Y-linked genes in human.

    Science.gov (United States)

    Nath Choudhury, Monisha; Uddin, Arif; Chakraborty, Supriyo

    2017-08-01

    The non-uniform usage of synonymous codons during translation of a protein is the codon usage bias and is mainly influenced by natural selection and mutation pressure. We have used bioinformatic approaches to analyze codon usage bias of human Y-linked genes. Effective number of codon (ENC) suggested that the overall extent of codon usage bias of genes was low. The relative synonymous codon usage (RSCU) analysis revealed that AGA and CTG codons were over-represented in Y-linked genes. Compositional constraint under mutation pressure influenced the codon usage pattern as revealed by the correspondence analysis (COA). Parity plot suggests that both natural selection and mutation pressure might have influenced the codon usage bias of Y-linked genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Olive response to water availability: yield response functions, soil water content indicators and evaluation of adaptability to climate change

    Science.gov (United States)

    Riccardi, Maria; Alfieri, Silvia Maria; Basile, Angelo; Bonfante, Antonello; Menenti, Massimo; Monaco, Eugenia; De Lorenzi, Francesca

    2013-04-01

    simulation model of the water flow in the soil-plant-atmosphere system, the indicators of soil water availability were calculated for different soil units in an area of Southern Italy, traditionally cultivated with olive. Simulations were performed for two climate scenarios: reference (1961-90) and future climate (2021-50). The potentiality of the indicators RSWD, RED and RTD to describe soil water availability was evaluated using simulated and experimental data. The analysis showed that RED values were correlated to RTD. The analysis demonstrated that RTD was more effective than RED in representing crop water availability RSWD is very well correlated to RTD and the degree of correlation depends of the period of deficit considered. The probability of adaptation of each cultivar was calculated for both climatic periods by comparing the critical values (and their error distribution) with soil availability indicators. Keywords: Olea europaea, soil water deficit, water availability critical value. The work was carried out within the Italian national project AGROSCENARI funded by the Ministry for Agricultural, Food and Forest Policies (MIPAAF, D.M. 8608/7303/2008)

  10. Synonymous codon usage analysis of hand, foot and mouth disease viruses: A comparative study on coxsackievirus A6, A10, A16, and enterovirus 71 from 2008 to 2015.

    Science.gov (United States)

    Su, Weiheng; Li, Xue; Chen, Meili; Dai, Wenwen; Sun, Shiyang; Wang, Shuai; Sheng, Xin; Sun, Shixiang; Gao, Chen; Hou, Ali; Zhou, Yan; Sun, Bo; Gao, Feng; Xiao, Jingfa; Zhang, Zhewen; Jiang, Chunlai

    2017-09-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) have been considered major pathogens of hand, foot and mouth disease (HFMD) throughout the world for decades. In recent years, coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) have raised attention as two other serious pathogens of HFMD. The present study focused on the synonymous codon usage of four viruses isolated from 2008 to 2015, with particular attention on P1 (encoding capsid proteins) and P2-P3 regions (both encoding non-structural proteins) in the genomic RNA. Relative synonymous codon usage, effective number of codons, neutrality and correspondence were analyzed. The results indicated that these viruses prefer A/T at the third position in codons rather than G/C. The most frequent codons of 4 essential and 2 semi-essential amino acids, as well as a key amino acid of metabolic junctions (Glu) used in the four viruses are also the most frequently used in humans. Effective number of codons (ENC) values indicated weak codon usage bias in all the viruses. Relatively, the force of mutation pressure in the P1 region was found to be stronger than that in the P2-P3 region, and this force in the P1 region of CVA6 and EV71 was stronger than that of CVA10 and A16. The neutrality analysis results implied that mutation pressure plays a minor role in shaping codon bias of these viruses. Correspondence analysis indicated that the codon usage of EV71 strains varied much more than that of other viruses. In conclusion, the present study provides novel and comparative insight into the evolution of HFMD pathogens at the codon level. Copyright © 2017. Published by Elsevier B.V.

  11. Codon-optimized antibiotic resistance gene improves efficiency of ...

    Indian Academy of Sciences (India)

    2013-10-01

    Oct 1, 2013 ... native gentamicin resistance gene, suggesting that codon optimization improved translation efficiency of the marker gene and ... to be taken into account when exogenous transgenes are expressed in Frankia cells. [Kucho K, Kakoi K, ..... gene coding for the green fluorescent protein (GFP) is a versatile ...

  12. Nonneutral GC3 and retroelement codon mimicry in Phytophthora

    NARCIS (Netherlands)

    Jiang, R.H.Y.; Govers, F.

    2006-01-01

    Phytophthora is a genus entirely comprised of destructive plant pathogens. It belongs to the Stramenopila, a unique branch of eukaryotes, phylogenetically distinct from plants, animals, or fungi. Phytophthora genes show a strong preference for usage of codons ending with G or C (high GC3). The

  13. Establishment and comparison of three different codon optimization ...

    African Journals Online (AJOL)

    C. elegan). It can raise the n-3/n-6 polyunsaturated fatty acids (PUFAs) ratio in mammalian cells. To reveal the impact of different codon optimizations of fat1 gene in influencing the catalysis efficiency of n-6 PUFAs into n-3 PUFAs in mammalian ...

  14. Establishment and comparison of three different codon optimization ...

    African Journals Online (AJOL)

    Yomi

    2012-02-16

    Feb 16, 2012 ... Arabidopsis. Proc. Natl. Acad. Sci. USA. 94: 1142-1147. Stothard P (2000). The sequence manipulation suite: JavaScript programs for analyzing and formatting protein and DNA sequences. Biotechniques, 28: 1102-1104. Wright F (1990). The 'effective number of codons' used in a gene. Gene. 87: 23-29.

  15. Improved secretory production of calf prochymosin by codon ...

    African Journals Online (AJOL)

    Chymosin as an important industrial enzyme used widely in cheese manufacture. In our preliminary study, low yields (80 U mL-1) were obtained when Kluyveromyces lactis GG799 was used to express chymosin. We investigated whether this poor secretion could be improved by codon optimization and disruption of PMR1 ...

  16. Codon usage determines translation rate in Escherichia coli

    DEFF Research Database (Denmark)

    Sørensen, Michael Askvad; Kurland, C G; Pedersen, Steen

    1989-01-01

    We wish to determine whether differences in translation rate are correlated with differences in codon usage or with differences in mRNA secondary structure. We therefore inserted a small DNA fragment in the lacZ gene either directly or flanked by a few frame-shifting bases, leaving the reading fr...

  17. Comparative studies on codon usage pattern of chloroplasts and ...

    Indian Academy of Sciences (India)

    Unknown

    and Bacillus subtilis, it is generally agreed that codon usage is attributable to the equilibrium between natural selection and compositional mutation bias (Bulmer 1988;. Sharp et al. 1993). This paradigm has been successfully applied to several eukaryotes such as Saccharomyces cerevisiae (Sharp et al. 1986), Drosophila ...

  18. Simple and efficient expression of codon-optimized mouse leukemia ...

    African Journals Online (AJOL)

    Purpose: To obtain a higher yield of mouse leukemia inhibitory factor to maintain the proliferation potential of pluripotent stem cells at a low cost. Methods: A method was designed to produce recombinant mLIF protein (rmLIF) in Escherichia coli. Through analysis of rmLIF sequence, it was found that rare codons were ...

  19. Codon-optimized antibiotic resistance gene improves efficiency of ...

    Indian Academy of Sciences (India)

    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 ...

  20. Improved secretory production of calf prochymosin by codon ...

    African Journals Online (AJOL)

    Administrator

    2011-09-12

    Sep 12, 2011 ... Chymosin as an important industrial enzyme used widely in cheese manufacture. In our preliminary study, low yields (80 U mL-1) were obtained when Kluyveromyces lactis GG799 was used to express chymosin. We investigated whether this poor secretion could be improved by codon optimization and.

  1. Codon-optimized antibiotic resistance gene improves efficiency of ...

    Indian Academy of Sciences (India)

    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 ...

  2. Synonymous codon usage in different protein secondary structural ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    2007-06-21

    Jun 21, 2007 ... However, when the genes were classified according to their GC3 levels there was an increase in non-randomness in high GC3 ... each of the protein secondary structural unit there exist some synonymous family that shows class specific codon- ... class by SCOP database are removed from our analysis.

  3. Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity.

    Science.gov (United States)

    Ivanov, Ivaylo P; Wei, Jiajie; Caster, Stephen Z; Smith, Kristina M; Michel, Audrey M; Zhang, Ying; Firth, Andrew E; Freitag, Michael; Dunlap, Jay C; Bell-Pedersen, Deborah; Atkins, John F; Sachs, Matthew S

    2017-06-27

    Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5' leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5' region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5' conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs) in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression. IMPORTANCE There is a deepening and widening appreciation of the diverse roles of translation in controlling gene expression. A central fungal transcription factor, the best-studied example of which is Saccharomyces cerevisiae GCN4, is crucial for the response to amino acid limitation. Two upstream open reading frames (uORFs) in the GCN4 mRNA are critical for controlling GCN4 synthesis. We observed that two uORFs in the corresponding Neurospora crassa cpc-1 mRNA appear functionally analogous to the GCN4 uORFs. We also discovered that, surprisingly, unlike GCN4, the CPC1 coding sequence extends far

  4. Detection of human papillomavirus DNA and p53 codon 72 polymorphism in prostate carcinomas of patients from Argentina

    Directory of Open Access Journals (Sweden)

    Kahn Tomas

    2005-11-01

    Full Text Available Abstract Background Infections with high-risk human papillomaviruses (HPVs, causatively linked to cervical cancer, might also play a role in the development of prostate cancer. Furthermore, the polymorphism at codon 72 (encoding either arginine or proline of the p53 tumor-suppressor gene is discussed as a possible determinant for cancer risk. The HPV E6 oncoprotein induces degradation of the p53 protein. The aim of this study was to analyse prostate carcinomas and hyperplasias of patients from Argentina for the presence of HPV DNA and the p53 codon 72 polymorphism genotype. Methods HPV DNA detection and typing were done by consensus L1 and type-specific PCR assays, respectively, and Southern blot hybridizations. Genotyping of p53 codon 72 polymorphism was performed both by allele specific primer PCRs and PCR-RFLP (Bsh1236I. Fischer's test with Woolf's approximation was used for statistical analysis. Results HPV DNA was detected in 17 out of 41 (41.5 % carcinoma samples, whereas all 30 hyperplasia samples were HPV-negative. Differences in p53 codon 72 allelic frequencies were not observed, neither between carcinomas and hyperplasias nor between HPV-positive and HPV-negative carcinomas. Conclusion These results indicate that the p53 genotype is probably not a risk factor for prostate cancer, and that HPV infections could be associated with at least a subset of prostate carcinomas.

  5. Exploring codon optimization and response surface methodology to express biologically active transmembrane RANKL in E. coli.

    Science.gov (United States)

    Maharjan, Sushila; Singh, Bijay; Bok, Jin-Duck; Kim, Jeong-In; Jiang, Tao; Cho, Chong-Su; Kang, Sang-Kee; Choi, Yun-Jaie

    2014-01-01

    Receptor activator of nuclear factor (NF)-κB ligand (RANKL), a master cytokine that drives osteoclast differentiation, activation and survival, exists in both transmembrane and extracellular forms. To date, studies on physiological role of RANKL have been mainly carried out with extracellular RANKL probably due to difficulties in achieving high level expression of functional transmembrane RANKL (mRANKL). In the present study, we took advantage of codon optimization and response surface methodology to optimize the soluble expression of mRANKL in E. coli. We optimized the codon usage of mRANKL sequence to a preferred set of codons for E. coli changing its codon adaptation index from 0.64 to 0.76, tending to increase its expression level in E. coli. Further, we utilized central composite design to predict the optimum combination of variables (cell density before induction, lactose concentration, post-induction temperature and post-induction time) for the expression of mRANKL. Finally, we investigated the effects of various experimental parameters using response surface methodology. The best combination of response variables was 0.6 OD600, 7.5 mM lactose, 26°C post-induction temperature and 5 h post-induction time that produced 52.4 mg/L of fusion mRANKL. Prior to functional analysis of the protein, we purified mRANKL to homogeneity and confirmed the existence of trimeric form of mRANKL by native gel electrophoresis and gel filtration chromatography. Further, the biological activity of mRANKL to induce osteoclast formation on RAW264.7 cells was confirmed by tartrate resistant acid phosphatase assay and quantitative real-time polymerase chain reaction assays. Importantly, a new finding from this study was that the biological activity of mRANKL is higher than its extracellular counterpart. To the best of our knowledge, this is the first time to report heterologous expression of mRANKL in soluble form and to perform a comparative study of functional properties of both

  6. Exploring codon optimization and response surface methodology to express biologically active transmembrane RANKL in E. coli.

    Directory of Open Access Journals (Sweden)

    Sushila Maharjan

    Full Text Available Receptor activator of nuclear factor (NF-κB ligand (RANKL, a master cytokine that drives osteoclast differentiation, activation and survival, exists in both transmembrane and extracellular forms. To date, studies on physiological role of RANKL have been mainly carried out with extracellular RANKL probably due to difficulties in achieving high level expression of functional transmembrane RANKL (mRANKL. In the present study, we took advantage of codon optimization and response surface methodology to optimize the soluble expression of mRANKL in E. coli. We optimized the codon usage of mRANKL sequence to a preferred set of codons for E. coli changing its codon adaptation index from 0.64 to 0.76, tending to increase its expression level in E. coli. Further, we utilized central composite design to predict the optimum combination of variables (cell density before induction, lactose concentration, post-induction temperature and post-induction time for the expression of mRANKL. Finally, we investigated the effects of various experimental parameters using response surface methodology. The best combination of response variables was 0.6 OD600, 7.5 mM lactose, 26°C post-induction temperature and 5 h post-induction time that produced 52.4 mg/L of fusion mRANKL. Prior to functional analysis of the protein, we purified mRANKL to homogeneity and confirmed the existence of trimeric form of mRANKL by native gel electrophoresis and gel filtration chromatography. Further, the biological activity of mRANKL to induce osteoclast formation on RAW264.7 cells was confirmed by tartrate resistant acid phosphatase assay and quantitative real-time polymerase chain reaction assays. Importantly, a new finding from this study was that the biological activity of mRANKL is higher than its extracellular counterpart. To the best of our knowledge, this is the first time to report heterologous expression of mRANKL in soluble form and to perform a comparative study of functional

  7. Coupling Between Protein Level Selection and Codon Usage Optimization in the Evolution of Bacteria and Archaea

    OpenAIRE

    Ran, Wenqi; Kristensen, David M.; Koonin, Eugene V.

    2014-01-01

    ABSTRACT The relationship between the selection affecting codon usage and selection on protein sequences of orthologous genes in diverse groups of bacteria and archaea was examined by using the Alignable Tight Genome Clusters database of prokaryote genomes. The codon usage bias is generally low, with 57.5% of the gene-specific optimal codon frequencies (F opt ) being below 0.55. This apparent weak selection on codon usage contrasts with the strong purifying selection on amino acid sequences, ...

  8. Low rates of bindin codon evolution in lecithotrophic Heliocidaris sea urchins.

    Science.gov (United States)

    Hart, Michael W; Popovic, Iva; Emlet, Richard B

    2012-06-01

    Life-history variables including egg size affect the evolutionary response to sexual selection in broadcast-spawning sea urchins and other marine animals. Such responses include high or low rates of codon evolution at gamete recognition loci that encode sperm- and egg-surface peptides. Strong positive selection on such loci affects intraspecific mating success and interspecific reproductive divergence (and may play a role in speciation). Here, we analyze adaptive codon evolution in the sperm acrosomal protein bindin from a brooding sea urchin (Heliocidaris bajulus, with large eggs and nonfeeding or lecithotrophic larval development) and compare our results to previously published data for two closely related congeners. Purifying selection and low relative rates of bindin nonsynonymous substitution in H. bajulus were significantly different from selectively neutral bindin evolution in H. erythrogramma despite similar large egg size in those two species, but were similar to the background rate of nonsynonymous bindin substitution for other closely related sea urchins (including H. tuberculata, all with small egg size and feeding planktonic larval development). Bindin evolution is not driven by egg size variation among Heliocidaris species, but may be more consistent with an alternative mechanism based on the effects of high or low spatial density of conspecific mates. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

  9. Comparative analysis of codon usage pattern and its influencing factors in Schistosoma japonicum and Ascaris suum.

    Science.gov (United States)

    Mazumder, Gulshana A; Uddin, Arif; Chakraborty, Supriyo

    2017-12-20

    Schistosoma japonicum and Ascaris suum are considered as the major parasites of human which cause various life threatening diseases such as schistomiasis and ascariasis. The codon usage bias (CUB) is known as the phenomenon of more usage of a specific codon than the other synonymous codons for an amino acid. The factors that influence the codon usage bias are mutation pressure, natural selection, gene expression, gene length, GC content, RNA stability, recombination rates, codon position etc. Here we had used various bioinformatic tools and statistical analyses to understand the compositional features, expression level and codon usage bias in the genes of these two species.After estimating the effective number of codon (ENC) in both the species, codon usage bias was found to be low and gene expression was high. The nucleobase A and T were used most often than C and G. From neutrality plot and correspondence analysis it was found that both natural selection and mutation pressure played an important role in shaping the codon usage pattern of both species. Moreover, natural selection played a major role while mutation pressure played a minor role in shaping the codon usage bias in S. japonicum and A.suum. This is the first report on the codon usage biology in S. japonicum and A.suum, and the factors influencing their codon usage bias. These results are expected to be useful for genetic engineering and evolutionary studies.

  10. Comparative mitogenomics of plant bugs (Hemiptera: Miridae: identifying the AGG codon reassignments between serine and lysine.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available Insect mitochondrial genomes are very important to understand the molecular evolution as well as for phylogenetic and phylogeographic studies of the insects. The Miridae are the largest family of Heteroptera encompassing more than 11,000 described species and of great economic importance. For better understanding the diversity and the evolution of plant bugs, we sequence five new mitochondrial genomes and present the first comparative analysis of nine mitochondrial genomes of mirids available to date. Our result showed that gene content, gene arrangement, base composition and sequences of mitochondrial transcription termination factor were conserved in plant bugs. Intra-genus species shared more conserved genomic characteristics, such as nucleotide and amino acid composition of protein-coding genes, secondary structure and anticodon mutations of tRNAs, and non-coding sequences. Control region possessed several distinct characteristics, including: variable size, abundant tandem repetitions, and intra-genus conservation; and was useful in evolutionary and population genetic studies. The AGG codon reassignments were investigated between serine and lysine in the genera Adelphocoris and other cimicomorphans. Our analysis revealed correlated evolution between reassignments of the AGG codon and specific point mutations at the antidocons of tRNALys and tRNASer(AGN. Phylogenetic analysis indicated that mitochondrial genome sequences were useful in resolving family level relationship of Cimicomorpha. Comparative evolutionary analysis of plant bug mitochondrial genomes allowed the identification of previously neglected coding genes or non-coding regions as potential molecular markers. The finding of the AGG codon reassignments between serine and lysine indicated the parallel evolution of the genetic code in Hemiptera mitochondrial genomes.

  11. Codon usage variation of Zika virus: The potential roles of NS2B and NS4A in its global pandemic.

    Science.gov (United States)

    Lin, Dechun; Li, Liqiang; Xie, Tian; Yin, Qingqing; Saksena, Nitin; Wu, Rangke; Li, Wanyu; Dai, Geyang; Ma, Jinmin; Zhou, Xiaohong; Chen, Xiaoguang

    2018-03-02

    A comprehensive demonstration of Zika virus (ZIKV) molecular evolution is essential for understanding its adaptation and expansion in its recent pandemics. Despite several studies on mutations and codon usage in ZIKVs, the variations in codon usage patterns across individual genes and their biological implication remains unclear. Here, we performed a gene-by-gene comparison of the codon usage variation in ZIKVs of the African and Asian lineages. We found that besides the evidence of positive selection (Ka/Ks >1) in the Asian lineage of the ZIKV genome, codon usage patterns were gene-specific and codon usage variation of ZIKV genes, was possibly constrained by their individual functional features, such as transmembrane domains, or antigenicity. In particular, the NS2B and NS4A genes showed distinct codon usage patterns, clearly separating them from the clusters of other genes in the correspondence analysis (CA). In the Asian lineage, the NS2B and NS4A genes showed the highest codon usage bias (ENC values: 51.01 ± 0.72 and 48.89 ± 0.99 respectively), and were subjected to the highest translation selection (ENC obs /ENC exp ratio: 0.847 ± 0.0297 and 0.828 ± 0.0233 respectively) in comparison to the African lineages of ZIKV. The CpG frequency of the NS2B showed a gradual ascending trend in the Asian ZIKV lineages, while in NS4A it was constrained along with the expansion of the Asian lineage. Furthermore, between the African and Asian lineages, differentiated and specific over-represented codons were more prominent in the NS2B and NS4A. Together, our study implies that ZIKVs are in the process of evolutionary fine tuning their codon as seen in the recent pandemics, and NS2B and NS4A could have played a potential role in the molecular evolution of the Asian lineage and their establishment. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. METHOD OF GROUP ADAPTATION WITH FIXING OF BIASES OF NEURONS (AFBN FOR FORECASTING OF INDICATORS OF QUALITY OF VOLUME ANNOUNCERS

    Directory of Open Access Journals (Sweden)

    S. V. Bukharin

    2015-01-01

    Full Text Available Neural modeling often doesn't guarantee performance of the principle of a community – the neural model trained on one data set can be not adequate when giving on its entrance of data from other set. Therefore when using neural modeling procedure of testing of the received results by means of the method of ridge regression based on the theory of regularization incorrectly of objectives is necessary. The being of the offered method of adaptation of a neural network with fixing of shifts (ABNS is as follows: 1. Instead of a two-layer neural network for adaptation the single-layer neural network more fully answering to use of a method of characteristic points as which the weighed sums of separate groups of signs get out is recommended. 2. For elimination of a problem of the ambiguity caused by a traditional choice of casual entry conditions, initial values of scales and shifts of neurons get out equal to zero. 3. For methodological unity of the solution of a straight line and the return problem of examination, on weight and shift of a neural network the following restrictions are programmatically imposed: the weight [0, 1], and shifts forcibly rely equal to zero by an adaptation speed parameter choice. 4. Results of neural modeling can often be doubtful owing to violation of the principle of a community and check of its observance requires obligatory testing of the received results, for example, by means of a method of ridge regression. As appears from the presented results, in all cases it is necessary to use the offered methods of consecutive and group adaptation with fixing of shifts of neurons, as thus there is a possibility of restoration of initial regression model. When fixing zero shifts of neurons their found weight gain values from the range [0, 1] that provides methodological unity of the solution of a straight line and return problem of examination.

  13. Reduced Protein Expression in a Virus Attenuated by Codon Deoptimization

    Directory of Open Access Journals (Sweden)

    Benjamin R. Jack

    2017-09-01

    Full Text Available A general means of viral attenuation involves the extensive recoding of synonymous codons in the viral genome. The mechanistic underpinnings of this approach remain unclear, however. Using quantitative proteomics and RNA sequencing, we explore the molecular basis of attenuation in a strain of bacteriophage T7 whose major capsid gene was engineered to carry 182 suboptimal codons. We do not detect transcriptional effects from recoding. Proteomic observations reveal that translation is halved for the recoded major capsid gene, and a more modest reduction applies to several coexpressed downstream genes. We observe no changes in protein abundances of other coexpressed genes that are encoded upstream. Viral burst size, like capsid protein abundance, is also decreased by half. Together, these observations suggest that, in this virus, reduced translation of an essential polycistronic transcript and diminished virion assembly form the molecular basis of attenuation.

  14. Codon Distribution in Error-Detecting Circular Codes.

    Science.gov (United States)

    Fimmel, Elena; Strüngmann, Lutz

    2016-03-15

    In 1957, Francis Crick et al. suggested an ingenious explanation for the process of frame maintenance. The idea was based on the notion of comma-free codes. Although Crick's hypothesis proved to be wrong, in 1996, Arquès and Michel discovered the existence of a weaker version of such codes in eukaryote and prokaryote genomes, namely the so-called circular codes. Since then, circular code theory has invariably evoked great interest and made significant progress. In this article, the codon distributions in maximal comma-free, maximal self-complementary C³ and maximal self-complementary circular codes are discussed, i.e., we investigate in how many of such codes a given codon participates. As the main (and surprising) result, it is shown that the codons can be separated into very few classes (three, or five, or six) with respect to their frequency. Moreover, the distribution classes can be hierarchically ordered as refinements from maximal comma-free codes via maximal self-complementary C(3) codes to maximal self-complementary circular codes.

  15. Codon Distribution in Error-Detecting Circular Codes

    Directory of Open Access Journals (Sweden)

    Elena Fimmel

    2016-03-01

    Full Text Available In 1957, Francis Crick et al. suggested an ingenious explanation for the process of frame maintenance. The idea was based on the notion of comma-free codes. Although Crick’s hypothesis proved to be wrong, in 1996, Arquès and Michel discovered the existence of a weaker version of such codes in eukaryote and prokaryote genomes, namely the so-called circular codes. Since then, circular code theory has invariably evoked great interest and made significant progress. In this article, the codon distributions in maximal comma-free, maximal self-complementary C3 and maximal self-complementary circular codes are discussed, i.e., we investigate in how many of such codes a given codon participates. As the main (and surprising result, it is shown that the codons can be separated into very few classes (three, or five, or six with respect to their frequency. Moreover, the distribution classes can be hierarchically ordered as refinements from maximal comma-free codes via maximal self-complementary C3 codes to maximal self-complementary circular codes.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    Mitarai, Namiko; Pedersen, Steen

    2013-01-01

    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...

  18. Investigating low adaptive behaviour and presence of the triad of impairments characteristic of autistic spectrum disorder as indicators of risk for challenging behaviour among adults with intellectual disabilities.

    Science.gov (United States)

    Felce, D; Kerr, M

    2013-02-01

    Identification of possible personal indicators of risk for challenging behaviour has generally been through association in cross-sectional prevalence studies, but few analyses have controlled for intercorrelation between potential risk factors. The aim was to investigate the extent to which gender, age, presence of the triad of impairments characteristic of autism and level of adaptive behaviour were independently associated with level of challenging behaviour among adults with intellectual disabilities. Five datasets were merged to produce information on challenging behaviour, adaptive behaviour, presence of the triad of impairments, gender and age of 818 adults. Variables were entered into a multivariate linear regression, which also tested the interaction between the presence of the triad of impairments and level of adaptive behaviour. Presence of the triad of impairments, level of adaptive behaviour, their interaction, and age, but not gender, significantly and independently contributed to the prediction of challenging behaviour. Presence/absence of the triad of impairments moderated the effect of adaptive behaviour on challenging behaviour. The inverse relationship found in the absence of the triad of impairments was virtually removed when present. This study has shown that it is necessary to control for intercorrelation between potential risk factors for challenging behaviour and to explore how interaction between them might moderate associations. © 2012 The Author. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

  19. Non-destructive indication of plastic deformation of cold-rolled stainless steel by magnetic adaptive testing

    Czech Academy of Sciences Publication Activity Database

    Vértesy, G.; Tomáš, Ivan; Mészáros, I.

    2007-01-01

    Roč. 310, - (2007), s. 76-82 ISSN 0304-8853 R&D Projects: GA AV ČR 1QS100100508; GA ČR(CZ) GA102/06/0866 Grant - others:HSRF(HU) T-035264; HSRF(HU) T-062466 Institutional research plan: CEZ:AV0Z10100520 Keywords : non-destructive testing * magnetic adaptive testing * ferromagnetic material * magnetization curve * hysteresis-magnetic Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.704, year: 2007

  20. The rare codon AGA is involved in regulation of pyoluteorin biosynthesis in Pseudomonas protegens Pf-5

    Directory of Open Access Journals (Sweden)

    Qing eYan

    2016-04-01

    Full Text Available 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. This 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 tRNAArgUCU, 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.

  1. Dependency of codon usage on protein sequence patterns: a statistical study

    Science.gov (United States)

    2014-01-01

    Background Codon degeneracy and codon usage by organisms is an interesting and challenging problem. Researchers demonstrated the relation between codon usage and various functions or properties of genes and proteins, such as gene regulation, translation rate, translation efficiency, mRNA stability, splicing, and protein domains. Researchers usually represent segments of proteins responsible for specific functions or structures in a family of proteins as sequence patterns or motifs. We asked the question if organisms use the same codons in pattern segments as compared to the rest of the sequence. Methods We used the likelihood ratio test, Pearson’s chi-squared test, and mutual information to compare these two codon usages. Results We showed that codon usage, in segments of genes that code for a given pattern or motif in a group of proteins, varied from the rest of the gene. The codon usage in these segments was not random. Amino acids with larger number of codons used more specific codon ratios in these segments. We studied the number of amino acids in the pattern (pattern length). As patterns got longer, there was a slight decrease in the fraction of patterns with significant different codon usage in the pattern region as compared to codon usage in the gene region. We defined a measure of specificity of protein patterns, and studied its relation to the codon usage. The difference in the codon usage between pattern region and gene region, was less for the patterns with higher specificity. Conclusions We provided a hypothesis that there are segments on genes that affect the codon usage and thus influence protein translation speed, and these regions are the regions that code protein pattern regions. PMID:24410898

  2. Idiosyncratic recognition of UUG/UUA codons by modified nucleoside 5-taurinomethyluridine, τm5U present at 'wobble' position in anticodon loop of tRNALeu: A molecular modeling approach.

    Directory of Open Access Journals (Sweden)

    Asmita S Kamble

    Full Text Available Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (τm5U at the 'wobble' 34th position in tRNALeu causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS. The τm5U34 specifically recognizes UUG and UUA codons. Structural consequences of τm5U34 to read cognate codons have not been studied so far in detail at the atomic level. Hence, 50ns multiple molecular dynamics (MD simulations of various anticodon stem loop (ASL models of tRNALeu in presence and absence of τm5U34 along with UUG and UUA codons were performed to explore the dynamic behaviour of τm5U34 during codon recognition process. The MD simulation results revealed that τm5U34 recognizes G/A ending codons by 'wobble' as well as a novel 'single' hydrogen bonding interactions. RMSD and RMSF values indicate the comparative stability of the ASL models containing τm5U34 modification over the other models, lacking τm5U34. Another MD simulation study of 55S mammalian mitochondrial rRNA with tRNALeu showed crucial interactions between the A-site residues, A918, A919, G256 and codon-anticodon bases. Thus, these results could improve our understanding about the decoding efficiency of human mt tRNALeu with τm5U34 to recognize UUG and UUA codons.

  3. Adaptation of benthic invertebrates to food sources along marine-terrestrial boundaries as indicated by carbon and nitrogen stable isotopes

    Science.gov (United States)

    Lange, G.; Haynert, K.; Dinter, T.; Scheu, S.; Kröncke, I.

    2018-01-01

    Frequent environmental changes and abiotic gradients of the Wadden Sea require appropriate adaptations of the local organisms and make it suitable for investigations on functional structure of macrozoobenthic communities from marine to terrestrial boundaries. To investigate community patterns and food use of the macrozoobenthos, a transect of 11 stations was sampled for species number, abundance and stable isotope values (δ13C and δ15N) of macrozoobenthos and for stable isotope values of potential food resources. The transect was located in the back-barrier system of the island of Spiekeroog (southern North Sea, Germany). Our results show that surface and subsurface deposit feeders, such as Peringia ulvae and different oligochaete species, dominated the community, which was poor in species, while species present at the transect stations reached high abundance. The only exception was the upper salt marsh with low abundances but higher species richness because of the presence of specialized semi-terrestrial and terrestrial taxa. The macrozoobenthos relied predominantly on marine resources irrespective of the locality in the intertidal zone, although δ13C values of the consumers decreased from - 14.1 ± 1.6‰ (tidal flats) to - 21.5 ± 2.4‰ (salt marsh). However, the ubiquitous polychaete Hediste diversicolor showed a δ15N enrichment of 2.8‰ (an increase of about one trophic level) from bare sediments to the first vegetated transect station, presumably due to switching from suspension or deposit feeding to predation on smaller invertebrates. Hence, we conclude that changes in feeding mode represent an important mechanism of adaptation to different Wadden Sea habitats.

  4. [Quality of care indicators for the care of human immunodeficiency virus-infected individuals, adapted to the pediatric age].

    Science.gov (United States)

    Soler-Palacín, Pere; Provens, Ana Clara; Martín-Nalda, Andrea; Espiau, María; Fernández-Polo, Aurora; Figueras, Concepció

    2014-03-01

    Since infection with human immunodeficiency virus (HIV) was first described, there have been many advances in its diagnosis, monitoring and treatment. However, few contributions are related to the area of health care quality. In this sense, the Spanish Study Group on AIDS (GESIDA) has developed a set of quality care indicators for adult patients living with HIV infection that includes a total of 66 indicators, 22 of which are considered to be relevant. Standards were calculated for each of them in order to reflect the level of the quality of care offered to these patients. Similar documents for pediatric patients are currently lacking. Preparation of a set of quality care indicators applicable to pediatric patients based on the GESIDA document and the Spanish Guidelines for monitoring of pediatric patients infected with HIV. Each indicator was analysed with respect to the required standards in all patients under 18 years of age followed-up in our Unit, with the aim of evaluating the quality of care provided. A total of 61 indicators were collected (51 from the GESIDA document and 10 from currently available pediatric guidelines), 30 of which were considered to be relevant. An overall compliance of 81%-83% was obtained when assessing the relevant indicators. The availability of health care quality standards is essential for the care of pediatric HIV-infected patients. The assessment of these indicators in our Unit yielded satisfactory results. Copyright © 2012 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  5. Development of a codon optimization strategy using the efor RED reporter gene as a test case

    Science.gov (United States)

    Yip, Chee-Hoo; Yarkoni, Orr; Ajioka, James; Wan, Kiew-Lian; Nathan, Sheila

    2018-04-01

    Synthetic biology is a platform that enables high-level synthesis of useful products such as pharmaceutically related drugs, bioplastics and green fuels from synthetic DNA constructs. Large-scale expression of these products can be achieved in an industrial compliant host such as Escherichia coli. To maximise the production of recombinant proteins in a heterologous host, the genes of interest are usually codon optimized based on the codon usage of the host. However, the bioinformatics freeware available for standard codon optimization might not be ideal in determining the best sequence for the synthesis of synthetic DNA. Synthesis of incorrect sequences can prove to be a costly error and to avoid this, a codon optimization strategy was developed based on the E. coli codon usage using the efor RED reporter gene as a test case. This strategy replaces codons encoding for serine, leucine, proline and threonine with the most frequently used codons in E. coli. Furthermore, codons encoding for valine and glycine are substituted with the second highly used codons in E. coli. Both the optimized and original efor RED genes were ligated to the pJS209 plasmid backbone using Gibson Assembly and the recombinant DNAs were transformed into E. coli E. cloni 10G strain. The fluorescence intensity per cell density of the optimized sequence was improved by 20% compared to the original sequence. Hence, the developed codon optimization strategy is proposed when designing an optimal sequence for heterologous protein production in E. coli.

  6. Codon Optimization in the Production of Recombinant Biotherapeutics: Potential Risks and Considerations.

    Science.gov (United States)

    Mauro, Vincent P

    2018-02-01

    Biotherapeutics are increasingly becoming the mainstay in the treatment of a variety of human conditions, particularly in oncology and hematology. The production of therapeutic antibodies, cytokines, and fusion proteins have markedly accelerated these fields over the past decade and are probably the major contributor to improved patient outcomes. Today, most protein therapeutics are expressed as recombinant proteins in mammalian cell lines. An expression technology commonly used to increase protein levels involves codon optimization. This approach is possible because degeneracy of the genetic code enables most amino acids to be encoded by more than one synonymous codon and because codon usage can have a pronounced influence on levels of protein expression. Indeed, codon optimization has been reported to increase protein expression by >  1000-fold. The primary tactic of codon optimization is to increase the rate of translation elongation by overcoming limitations associated with species-specific differences in codon usage and transfer RNA (tRNA) abundance. However, in mammalian cells, assumptions underlying codon optimization appear to be poorly supported or unfounded. Moreover, because not all synonymous codon mutations are neutral, codon optimization can lead to alterations in protein conformation and function. This review discusses codon optimization for therapeutic protein production in mammalian cells.

  7. Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

    Science.gov (United States)

    Diaz de Arce, Alexander J; Noderer, William L; Wang, Clifford L

    2018-01-25

    The initiation of mRNA translation from start codons other than AUG was previously believed to be rare and of relatively low impact. More recently, evidence has suggested that as much as half of all translation initiation utilizes non-AUG start codons, codons that deviate from AUG by a single base. Furthermore, non-AUG start codons have been shown to be involved in regulation of expression and disease etiology. Yet the ability to gauge expression based on the sequence of a translation initiation site (start codon and its flanking bases) has been limited. Here we have performed a comprehensive analysis of translation initiation sites that utilize non-AUG start codons. By combining genetic-reporter, cell-sorting, and high-throughput sequencing technologies, we have analyzed the expression associated with all possible variants of the -4 to +4 positions of non-AUG translation initiation site motifs. This complete motif analysis revealed that 1) with the right sequence context, certain non-AUG start codons can generate expression comparable to that of AUG start codons, 2) sequence context affects each non-AUG start codon differently, and 3) initiation at non-AUG start codons is highly sensitive to changes in the flanking sequences. Complete motif analysis has the potential to be a key tool for experimental and diagnostic genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. New insights into the factors affecting synonymous codon usage in human infecting Plasmodium species.

    Science.gov (United States)

    Gajbhiye, Shivani; Patra, P K; Yadav, Manoj Kumar

    2017-12-01

    Codon usage bias is due to the non-random usage of synonymous codons for coding amino acids. The synonymous sites are under weak selection, and codon usage bias is maintained by the equilibrium in mutational bias, genetic drift and selection pressure. The differential codon usage choices are also relevant to human infecting Plasmodium species. Recently, P. knowlesi switches its natural host, long-tailed macaques, and starts infecting humans. This review focuses on the comparative analysis of codon usage choices among human infecting P. falciparum and P. vivax along with P. knowlesi species taking their coding sequence data. The variation in GC content, amino acid frequencies, effective number of codons and other factors plays a crucial role in determining synonymous codon choices. Within species codon choices are more similar for P. vivax and P. knowlesi in comparison with P. falciparum species. This study suggests that synonymous codon choice modulates the gene expression level, mRNA stability, ribosome speed, protein folding, translation efficiency and its accuracy in Plasmodium species, and provides a valuable information regarding the codon usage pattern to facilitate gene cloning as well as expression and transfection studies for malaria causing species. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Strand asymmetry and codon usage bias in the chloroplast genome of Euglena gracilis

    Science.gov (United States)

    Morton, Brian R.

    1999-01-01

    It is shown that the two strands of the chloroplast genome from Euglena gracilis are asymmetric with regards to nucleotide composition. This asymmetry switches at both the origin of replication and a location that is halfway around the circular genome from the origin. In both halves of the genome the leading strand is G+T-rich, having a bias toward G over C and T over A, and the lagging strand is A+C-rich. This asymmetry is probably the result of a difference in mutation dynamics between the leading and lagging strands. In addition to composition asymmetry, the two strands differ with regards to coding content. In both halves of the genome the vast majority of genes are coded by the leading strand. These two aspects of strand asymmetry are then applied to a statistical test for selection on codon usage. The results indicate that selection on codon usage is limited to genes on the leading strand; no gene on the A+C-rich lagging strand shows evidence for selection, suggesting that highly expressed genes are coded predominantly on the strand of DNA that is the leading strand during replication. On the basis of these observations it is proposed that the coding strand bias is generated by selection to code highly expressed genes on the leading strand to coordinate the direction of replication and transcription, thereby increasing the potential rate of both reactions. PMID:10220429

  10. Adaptive Spatial Filter Based on Similarity Indices to Preserve the Neural Information on EEG Signals during On-Line Processing.

    Science.gov (United States)

    Delisle-Rodriguez, Denis; Villa-Parra, Ana Cecilia; Bastos-Filho, Teodiano; López-Delis, Alberto; Frizera-Neto, Anselmo; Krishnan, Sridhar; Rocon, Eduardo

    2017-11-25

    This work presents a new on-line adaptive filter, which is based on a similarity analysis between standard electrode locations, in order to reduce artifacts and common interferences throughout electroencephalography (EEG) signals, but preserving the useful information. Standard deviation and Concordance Correlation Coefficient (CCC) between target electrodes and its correspondent neighbor electrodes are analyzed on sliding windows to select those neighbors that are highly correlated. Afterwards, a model based on CCC is applied to provide higher values of weight to those correlated electrodes with lower similarity to the target electrode. The approach was applied to brain computer-interfaces (BCIs) based on Canonical Correlation Analysis (CCA) to recognize 40 targets of steady-state visual evoked potential (SSVEP), providing an accuracy (ACC) of 86.44 ± 2.81%. In addition, also using this approach, features of low frequency were selected in the pre-processing stage of another BCI to recognize gait planning. In this case, the recognition was significantly ( p < 0.01 ) improved for most of the subjects ( A C C ≥ 74.79 % ) , when compared with other BCIs based on Common Spatial Pattern, Filter Bank-Common Spatial Pattern, and Riemannian Geometry.

  11. Adaptive Spatial Filter Based on Similarity Indices to Preserve the Neural Information on EEG Signals during On-Line Processing

    Directory of Open Access Journals (Sweden)

    Denis Delisle-Rodriguez

    2017-11-01

    Full Text Available This work presents a new on-line adaptive filter, which is based on a similarity analysis between standard electrode locations, in order to reduce artifacts and common interferences throughout electroencephalography (EEG signals, but preserving the useful information. Standard deviation and Concordance Correlation Coefficient (CCC between target electrodes and its correspondent neighbor electrodes are analyzed on sliding windows to select those neighbors that are highly correlated. Afterwards, a model based on CCC is applied to provide higher values of weight to those correlated electrodes with lower similarity to the target electrode. The approach was applied to brain computer-interfaces (BCIs based on Canonical Correlation Analysis (CCA to recognize 40 targets of steady-state visual evoked potential (SSVEP, providing an accuracy (ACC of 86.44 ± 2.81%. In addition, also using this approach, features of low frequency were selected in the pre-processing stage of another BCI to recognize gait planning. In this case, the recognition was significantly ( p < 0.01 improved for most of the subjects ( A C C ≥ 74.79 % , when compared with other BCIs based on Common Spatial Pattern, Filter Bank-Common Spatial Pattern, and Riemannian Geometry.

  12. p53 mutations and codon 213 polymorphism of p53 in lung cancers of former uranium miners.

    Science.gov (United States)

    Popp, W; Vahrenholz, C; Schuster, H; Wiesner, B; Bauer, P; Täuscher, F; Plogmann, H; Morgenroth, K; Konietzko, N; Norpoth, K

    1999-01-01

    There is a high prevalence of G-->T transversions of p53 in lung cancers of smokers. One study has reported a special "hotspot" mutation at codon 249 of p53 in lung cancers of former uranium miners. The aim of our study was to look for mutational spectra of p53 in former German uranium miners with lung cancers. We investigated 16 patients with lung cancer who had worked as uranium miners in Germany and 13 lung cancer patients without a mining history of the same region. By means of the polymerase chain reaction and sequencing we looked for mutations in exons 5 7 of the p53 gene. We could not find any suggestion of hotspot mutations. The only G-->T mutation in former uranium miners was detected in the only nonsmoker. In 3 patients (19% of the total) we found a codon 213/3 polymorphism. The results indicate that G-->T transversions do not seem to be very common mutations in p53 in lung cancers probably caused by radiation. Therefore, p53 may be mutated early in lung cancer development if radiation exposure is a critical factor in carcinogenesis. In accordance with studies of thyroid cancer patients in the Chernobyl region, our results may indicate an overrepresentation of codon 213/3 polymorphism in p53 in radiation-caused cancers.

  13. Danish version of the Tilburg Frailty Indicator – Translation, cross-cultural adaption and validity pretest by cognitive interviewing

    DEFF Research Database (Denmark)

    Andreasen, Jane; Sørensen, Erik E; Gobbens, Robbert J J

    2014-01-01

    The Tilburg Frailty Indicator (TFI) is a self-administered questionnaire with a bio-psycho-social integrated approach that measures the degree of frailty in elderly persons. The TFI was developed in the Netherlands and tested in a population of elderly Dutch men and women. The aim of this study w...

  14. Functional Versatility of AGY Serine Codons in Immunoglobulin Variable Region Genes

    Directory of Open Access Journals (Sweden)

    Thiago Detanico

    2016-11-01

    Full Text Available In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ag often arise by somatic hypermutation (SHM that converts AGT and AGC (AGY Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase (AID, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in anti-viral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses, and found that mutations producing Arg codons in anti-viral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with antigen (Ag. In many cases, mutations producing codons for these alternative amino acids in anti-viral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which 2/3rds of random mutations generate codons for these key residues. Finally, by directly analyzing x-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via somatic hypermutation occurred more often at AGY than at any other codon group. Thus, preservation of

  15. Using clinical indicators to facilitate quality improvement via the accreditation process: an adaptive study into the control relationship.

    Science.gov (United States)

    Chuang, Sheuwen; Howley, Peter P; Hancock, Stephen

    2013-07-01

    The aim of the study was to determine accreditation surveyors' and hospitals' use and perceived usefulness of clinical indicator reports and the potential to establish the control relationship between the accreditation and reporting systems. The control relationship refers to instructional directives, arising from appropriately designed methods and efforts towards using clinical indicators, which provide a directed moderating, balancing and best outcome for the connected systems. Web-based questionnaire survey. Australian Council on Healthcare Standards' (ACHS) accreditation and clinical indicator programmes. Seventy-three of 306 surveyors responded. Half used the reports always/most of the time. Five key messages were revealed: (i) report use was related to availability before on-site investigation; (ii) report use was associated with the use of non-ACHS reports; (iii) a clinical indicator set's perceived usefulness was associated with its reporting volume across hospitals; (iv) simpler measures and visual summaries in reports were rated the most useful; (v) reports were deemed to be suitable for the quality and safety objectives of the key groups of interested parties (hospitals' senior executive and management officers, clinicians, quality managers and surveyors). Implementing the control relationship between the reporting and accreditation systems is a promising expectation. Redesigning processes to ensure reports are available in pre-survey packages and refined education of surveyors and hospitals on how to better utilize the reports will support the relationship. Additional studies on the systems' theory-based model of the accreditation and reporting system are warranted to establish the control relationship, building integrated system-wide relationships with sustainable and improved outcomes.

  16. A Tool for the Sustainability Assessment of Farms: Selection, Adaptation and Use of Indicators for an Italian Case Study

    Directory of Open Access Journals (Sweden)

    Anna Gaviglio

    2017-10-01

    Full Text Available Indicator-based tools are widely used for the assessment of farm sustainability, but analysts still face methodological and conceptual issues, including data availability, the complexity of the concept of sustainability and the heterogeneity of agricultural systems. This study contributes to this debate through the illustration of a procedure for farm sustainability assessment focussed on the case study of the South Milan Agricultural Park, Italy. The application is based on a set of environmental, social and economic indicators retrieved from the literature review. The framework is based on three main steps: (i Data collection mainly through interviews with farmers and institutions; (ii data elaboration through an aggregative structure; and (iii score analysis. The latter step includes a descriptive analysis that allows a comparison among farms or groups of farms and a principal components analysis that helps to confirm the dimensions in which indicators were previously included (components. Results derived from the sampled farms show that the framework can provide easy-to-read results useful at different levels. The study highlighted the procedures for the framework construction that is compatible with the region’s context and objectives, using an analytical approach that aims at the use of balanced features of availability and reliability of data.

  17. Nature-based solutions to climate change mitigation and adaptation in urban areas: perspectives on indicators, knowledge gaps, barriers, and opportunities for action

    Directory of Open Access Journals (Sweden)

    Nadja Kabisch

    2016-06-01

    Full Text Available Nature-based solutions promoting green and blue urban areas have significant potential to decrease the vulnerability and enhance the resilience of cities in light of climatic change. They can thereby help to mitigate climate change-induced impacts and serve as proactive adaptation options for municipalities. We explore the various contexts in which nature-based solutions are relevant for climate mitigation and adaptation in urban areas, identify indicators for assessing the effectiveness of nature-based solutions and related knowledge gaps. In addition, we explore existing barriers and potential opportunities for increasing the scale and effectiveness of nature-based solution implementation. The results were derived from an inter- and transdisciplinary workshop with experts from research, municipalities, policy, and society. As an outcome of the workshop discussions and building on existing evidence, we highlight three main needs for future science and policy agendas when dealing with nature-based solutions: (i produce stronger evidence on nature-based solutions for climate change adaptation and mitigation and raise awareness by increasing implementation; (ii adapt for governance challenges in implementing nature-based solutions by using reflexive approaches, which implies bringing together new networks of society, nature-based solution ambassadors, and practitioners; (iii consider socio-environmental justice and social cohesion when implementing nature-based solutions by using integrated governance approaches that take into account an integrative and transdisciplinary participation of diverse actors. Taking these needs into account, nature-based solutions can serve as climate mitigation and adaptation tools that produce additional cobenefits for societal well-being, thereby serving as strong investment options for sustainable urban planning.

  18. Multi Media Dry Imager and printer: Codonics Medical Disc Publisher: Virtua

    OpenAIRE

    Eric Tual

    2007-01-01

    Multi media dry imager and printer: Codonics"nCodonics, a privately held corporation headquartered in Cleveland, Ohio, has been pioneering medical hardcopy solutions for over a decade, and is the industry leader in multi-media imagers. The first to introduce color DICOM printers, we are now represented in over 80 countries by thousands of people with over 25,000 installations worldwide. "nNow, Codonics revolutionizes the medical industry with the introduction of the Horizon Multi-me...

  19. Eukaryotic evolutionary transitions are associated with extreme codon bias in functionally-related proteins.

    Directory of Open Access Journals (Sweden)

    Nicholas J Hudson

    Full Text Available 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.

  20. Codon 219 polymorphism of PRNP in healthy caucasians and Creutzfeldt-Jakob disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Petraroli, R.; Pocchiari, M. [Instituto Superiore di Sanita, Rome (Italy)

    1996-04-01

    A number of point and insert mutations of the PrP gene (PRNP) have been linked to familial Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker disease (GSS). Moreover, the methionine/valine homozygosity at the polymorphic codon 129 of PRNP may cause a predisposition to sporadic and iatrogenic CJD or may control the age at onset of familial cases carrying either the 144-bp insertion or codon 178, codon 198, and codon 210 pathogenic mutations in PRNP. In addition, the association of methionine or valine at codon 129 and the point mutation at codon 178 on the same allele seem to play an important role in determining either fatal familial insomnia or CJD. However, it is noteworthy that a relationship between codon 129 polymorphism and accelerated pathogenesis (early age at onset or shorter duration of the disease) has not been seen in familial CJD patients with codon 200 mutation or in GSS patients with codon 102 mutation, arguing that other, as yet unidentified, gene products or environmental factors, or both, may influence the clinical expression of these diseases. 17 refs.

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

    International Nuclear Information System (INIS)

    Mitarai, Namiko; Pedersen, Steen

    2013-01-01

    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. (paper)

  2. Genome-wide analysis of codon usage bias in Bovine Coronavirus.

    Science.gov (United States)

    Castells, Matías; Victoria, Matías; Colina, Rodney; Musto, Héctor; Cristina, Juan

    2017-06-17

    Bovine coronavirus (BCoV) belong to the genus Betacoronavirus of the family Coronaviridae. BCoV are widespread around the world and cause enteric or respiratory infections among cattle, leading to important economic losses to the beef and dairy industry worldwide. To study the relation of codon usage among viruses and their hosts is essential to understand host-pathogen interaction, evasion from host's immune system and evolution. We performed a comprehensive analysis of codon usage and composition of BCoV. The global codon usage among BCoV strains is similar. Significant differences of codon preferences in BCoV genes in relation to codon usage of Bos taurus host genes were found. Most of the highly frequent codons are U-ending. G + C compositional constraint and dinucleotide composition also plays a role in the overall pattern of BCoV codon usage. The results of these studies revealed that mutational bias is a leading force shaping codon usage in this virus. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern.

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

    Science.gov (United States)

    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.

  4. Adaptation of a community-based participatory research model to gain community input on identifying indicators of successful parenting.

    Science.gov (United States)

    Zlotnick, Cheryl; Wright, Marguerite; Sanchez, Roberto Macias; Kusnir, Rosario Murga; Te'o-Bennett, Iemaima

    2010-01-01

    Parenting models are generally based on families in stable homes, rather than in transitional situations such as in foster care, homeless shelters, and other temporary, at-risk residences. Consequently, these models do not recognize the unique challenges of families in transition. This study explored the domains of the Circumplex Model and examined its fit for transitional families using tenets from community-based participatory research. Findings suggest that in addition to the Circumplex Model's components, caregivers with children living in transition believe that managing the scrutiny of external authority systems and countering the negative influences of poverty and racism are two indicators that contribute to parenting success. Obtaining consumer-informed views of parenting not only is an important contributor to standards of practice, but also a promising avenue for future research.

  5. Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice.

    Science.gov (United States)

    Wanner, Roger M; Güthlein, Carolin; Springer, Burkhard; Böttger, Erik C; Ackermann, Martin

    2008-05-28

    The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

  6. Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice

    Directory of Open Access Journals (Sweden)

    Ackermann Martin

    2008-05-01

    Full Text Available Abstract Background The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. Results We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. Conclusion These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

  7. A start codon CMT1X mutation associated with transient encephalomyelitis causes complete loss of Cx32.

    Science.gov (United States)

    Sargiannidou, Irene; Kim, Gun-Ha; Kyriakoudi, Styliana; Eun, Baik-Lin; Kleopa, Kleopas A

    2015-07-01

    X-linked Charcot-Marie-Tooth disease (CMTX1) results from numerous mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32) and is one of the commonest forms of inherited neuropathy. Owing to the expression of Cx32 not only in Schwann cells but also in oligodendrocytes, a subset of CMT1X patients develops central nervous system (CNS) clinical manifestations in addition to peripheral neuropathy. While most GJB1 mutations appear to cause peripheral neuropathy through loss of Cx32 function, the cellular mechanisms underlying the CNS manifestations remain controversial. A novel start codon GJB1 mutation (p.Met1Ile) has been found in a CMT1X patient presenting with recurrent episodes of transient encephalomyelitis without apparent signs of peripheral neuropathy. In order to clarify the functional consequences of this mutation, we examined the cellular expression of two different constructs cloned from genomic DNA including the mutated start codon. None of the cloned constructs resulted in detectable expression of Cx32 by immunocytochemistry or immunoblot, although mRNA was produced at normal levels. Furthermore, co-expression with the other major oligodendrocyte connexin, Cx47, had no negative effect on GJ formation by Cx47. Finally, lysosomal and proteasomal inhibition in cells expressing the start codon mutant constructs failed to recover any detection of Cx32 as a result of impaired protein degradation. Our results indicate that the Cx32 start codon mutation is equivalent to a complete loss of the protein with failure of translation, although transcription is not impaired. Thus, complete loss of Cx32 function is sufficient to produce CNS dysfunction with clinical manifestations.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-10-01

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

  9. Unique features of nucleotide and codon usage patterns in mycoplasmas revealed by information entropy.

    Science.gov (United States)

    Wang, Yi-Ning; Ji, Wen-Heng; Li, Xue-Rui; Liu, Yong-Sheng; Zhou, Jian-Hua

    2018-03-01

    Currently, the comparison between GC usage pattern at the 3rd codon position and codon usage index is commonly used to estimate the roles of evolutionary forces in shaping synonymous codon usages, however, this kind of analysis often losses the information about the role of A/T usage bias in shaping synonymous codon usage bias. To overcome this limitation and better understand the interplay between nucleotide and codon usages for the evolution of bacteria at gene levels, in this study, we employed the information entropy method with some modification to estimate roles of nucleotide compositions in the overall codon usage bias for 18 mycoplasma species in combination with Davies-Bouldin index. At gene levels, the overall nucleotide usage bias represents A content as the highest, followed by T, G and C for mycoplasmas, resulting in a low GC content. This feature is universal across these species derived from different hosts, suggesting that the hosts have the limited impact on nucleotide usage bias of mycoplasmas. Information entropy and Davies-Bouldin index can better reveal that the nucleotide usage bias at the 3rd codon position is essential in shaping the overall nucleotide bias for all given mycoplasmas except M. pneumoniae M129. Davies-Bouldin index revealed that the 1st and 2nd codon position play more important role in synonymous codon usage bias than that of the 3rd position at gene levels. To our knowledge, this is the first comprehensive investigation into cooperation between nucleotide and codon usages for mycoplasma and extends our knowledge of the mechanisms that contribute to codon usage and evolution of this microorganism. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Fuglsang, Anders

    2007-01-01

    The effective number of codons (Nc) used in a gene is one of the most commonly used measures of synonymous codon usage bias, owing much of its popularity to the fact that it is species independent and that simulation studies have shown that it is less dependent of gene length than other measures....... In this paper I provide a clear and practically meaningful definition of bias discrepancy (BD; when the degree of codon bias varies within a degeneracy class). Moreover I evaluate the impact of BD and amino acid usage on estimates of Nc. It is shown that both factors have a significant effect on accuracy...... and precision. Both amino acid usage and BD influence accuracy considerably, especially in short genes. Finally, I demonstrate how the definition of bias discrepancy can be applied to investigate if codon usage is influenced by selection and I discuss this test in relation to the incongruous literature...

  11. Open access to Water Indicators for Climate Change Adaptation: proof-of-concept for the Copernicus Climate Change Service (C3S)

    Science.gov (United States)

    Lottle, Lorna; Arheimer, Berit; Gyllensvärd, Frida; Dejong, Fokke; Ludwig, Fulco; Hutjes, Ronald; Martinez, Bernat

    2017-04-01

    Copernicus Climate Change Service (C3S) is still in the development phase and will combine observations of the climate system with the latest science to develop authoritative, quality-assured information about the past, current and future states of the climate and climate dependent sectors in Europe and worldwide. C3S will provide key indicators on climate change drivers and selected sectorial impacts. The aim of these indicators will be to support adaptation and mitigation. This presentation will show one service already operational as a proof-of-concept of this future climate service. The project "Service for Water Indicators in Climate Change Adaptation" (SWICCA) has developed a sectorial information service for water management. It offers readily available climate-impact data, for open access from the web-site http://swicca.climate.copernicus.eu/. The development is user-driven with the overall goal to speed up the workflow in climate-change adaptation of water management across Europe. The service is co-designed by consultant engineers and agencies in 15 case-studies spread out over the continent. SWICCA has an interactive user-interface, which shows maps and graphs, and facilitates data download in user-friendly formats. In total, more than 900 open dataset are given for various hydrometeorological (and a few socioeconomical) variables, model ensembles, resolutions, time-periods and RCPs. The service offers more than 40 precomputed climate impact indicators (CIIs) and transient time-series of 4 essential climate variables ECVs) with high spatial and temporal resolution. To facilitate both near future and far future assessments, SWICCA provides the indicators for different time ranges; normally, absolute values are given for a reference period (e.g. 1971-2000) and the expected future changes for different 30-year periods, such as early century (2011-2040), mid-century (2041-2070) and end-century (2071-2100). An ensemble of model results is always given to

  12. A Codon-Based Model of Host-Specific Selection in Parasites, with an Application to the Influenza A Virus

    DEFF Research Database (Denmark)

    Forsberg, Ronald; Christiansen, Freddy Bugge

    2003-01-01

    Parasites sometimes expand their host range by acquiring a new host species. Following a host change event, the selective regime acting on a given parasite gene may change due to host-specific adaptive alterations of protein functionality or host-specific immune-mediated selection. We present...... a codon-based model that attempts to include these effects by allowing the position-specific substitution process to change in conjunction with a host change event. Following maximum-likelihood parameter estimation, we employ an empirical Bayesian procedure to identify candidate sites, potentially...... involved in hostspecific adaptation. We discuss the applicability of the model to the more general problem of ascertaining whether the selective regime differs between two groups of related organisms. The utility of the model is illustrated on a dataset of nucleoprotein sequences from the influenza A virus...

  13. Protein evolution via amino acid and codon elimination

    DEFF Research Database (Denmark)

    Goltermann, Lise; Larsen, Marie Sofie Yoo; Banerjee, Rajat

    2010-01-01

    BACKGROUND: Global residue-specific amino acid mutagenesis can provide important biological insight and generate proteins with altered properties, but at the risk of protein misfolding. Further, targeted libraries are usually restricted to a handful of amino acids because there is an exponential...... correlation between the number of residues randomized and the size of the resulting ensemble. Using GFP as the model protein, we present a strategy, termed protein evolution via amino acid and codon elimination, through which simplified, native-like polypeptides encoded by a reduced genetic code were obtained...... simultaneously), while retaining varying levels of activity. Combination of these substitutions to generate a Phe-free variant of GFP abolished fluorescence. Combinatorial re-introduction of five Phe residues, based on the activities of the respective single amino acid replacements, was sufficient to restore GFP...

  14. RET codon 609 mutations: a contribution for better clinical managing

    Directory of Open Access Journals (Sweden)

    Caterina Mian

    2012-01-01

    Full Text Available Medullary thyroid carcinoma currently accounts for 5-8% of all thyroid cancers. The clinical course of this disease varies from extremely indolent tumors that can go unchanged for years to an extremely aggressive variant that is associated with a high mortality rate. As many as 75% of all medullary thyroid carcinomas are sporadic, with an average age at presentation reported as 60 years, and the remaining 25% are hereditary with an earlier age of presentation, ranging from 20 to 40 years. Germline RET proto-oncogene mutations are the genetic causes of multiple endocrine neoplasia type 2 and a strong genotype-phenotype correlation exists, particularly between a specific RET codon mutation and the (a age-related onset and (b thyroid tumor progression, from C-cell hyperplasia to medullary thyroid carcinoma and, ultimately, to nodal metastases. RET mutations predispose an individual to the development of medullary thyroid carcinomas and can also influence the individual response to RET protein receptor-targeted therapies. RET codon 609point mutations are rare genetic events belonging to the intermediate risk category for the onset of medullary thyroid carcinoma. A large genealogy resulting in a less aggressive form of medullary thyroid carcinoma is associated with the high penetrance of pheochromocytoma and has been reported in the literature. In this short review article, we comment on our previous report of a large multiple endocrine neoplasia type 2A kindred with the same Cys609Ser germline RET mutation in which, conversely, the syndrome was characterized by a slightly aggressive, highly penetrant form of medullary thyroid carcinoma that was associated with low penetrance of pheochromocytoma and primary hyperparathyroidism.

  15. Probable relationship between partitions of the set of codons and the origin of the genetic code.

    Science.gov (United States)

    Salinas, Dino G; Gallardo, Mauricio O; Osorio, Manuel I

    2014-03-01

    Here we study the distribution of randomly generated partitions of the set of amino acid-coding codons. Some results are an application from a previous work, about the Stirling numbers of the second kind and triplet codes, both to the cases of triplet codes having four stop codons, as in mammalian mitochondrial genetic code, and hypothetical doublet codes. Extending previous results, in this work it is found that the most probable number of blocks of synonymous codons, in a genetic code, is similar to the number of amino acids when there are four stop codons, as well as it could be for a primigenious doublet code. Also it is studied the integer partitions associated to patterns of synonymous codons and it is shown, for the canonical code, that the standard deviation inside an integer partition is one of the most probable. We think that, in some early epoch, the genetic code might have had a maximum of the disorder or entropy, independent of the assignment between codons and amino acids, reaching a state similar to "code freeze" proposed by Francis Crick. In later stages, maybe deterministic rules have reassigned codons to amino acids, forming the natural codes, such as the canonical code, but keeping the numerical features describing the set partitions and the integer partitions, like a "fossil numbers"; both kinds of partitions about the set of amino acid-coding codons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    Emery, Laura R.; Sharp, Paul M.

    2011-01-01

    Patterns of codon usage have been extensively studied among Bacteria and Eukaryotes, but there has been little investigation of species from the third domain of life, the Archaea. Here, we examine the nature of codon usage bias in a methanogenic archaeon, Methanococcus maripaludis. Genome-wide patterns of codon usage are dominated by a strong A + T bias, presumably largely reflecting mutation patterns. Nevertheless, there is variation among genes in the use of a subset of putatively translationally optimal codons, which is strongly correlated with gene expression level. In comparison with Bacteria such as Escherichia coli, the strength of selected codon usage bias in highly expressed genes in M. maripaludis seems surprisingly high given its moderate growth rate. However, the pattern of selected codon usage differs between M. maripaludis and E. coli: in the archaeon, strongly selected codon usage bias is largely restricted to twofold degenerate amino acids (AAs). Weaker bias among the codons for fourfold degenerate AAs is consistent with the small number of tRNA genes in the M. maripaludis genome. PMID:20810428

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

    Science.gov (United States)

    Emery, Laura R; Sharp, Paul M

    2011-02-23

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

  18. Codon usage biases co-evolve with transcription termination machinery to suppress premature cleavage and polyadenylation.

    Science.gov (United States)

    Zhou, Zhipeng; Dang, Yunkun; Zhou, Mian; Yuan, Haiyan; Liu, Yi

    2018-03-16

    Codon usage biases are found in all genomes and influence protein expression levels. The codon usage effect on protein expression was thought to be mainly due to its impact on translation. Here, we show that transcription termination is an important driving force for codon usage bias in eukaryotes. Using Neurospora crassa as a model organism, we demonstrated that introduction of rare codons results in premature transcription termination (PTT) within open reading frames and abolishment of full-length mRNA. PTT is a wide-spread phenomenon in Neurospora, and there is a strong negative correlation between codon usage bias and PTT events. Rare codons lead to the formation of putative poly(A) signals and PTT. A similar role for codon usage bias was also observed in mouse cells. Together, these results suggest that codon usage biases co-evolve with the transcription termination machinery to suppress premature termination of transcription and thus allow for optimal gene expression. © 2018, Zhou et al.

  19. Genus specific evolution of codon usage and nucleotide compositional traits of poxviruses.

    Science.gov (United States)

    Roychoudhury, Sourav; Pan, Archana; Mukherjee, Debaprasad

    2011-04-01

    Poxviruses are complex in their nucleotide compositional features of the coding regions. The codon usages in Poxviruses are in accordance with their compositional bias. In the Poxviridae family, codon usage patterns and nucleotide compositional traits are widely divergent across species but some conservation was observed within a genus. Viruses from six Chordopox genera, i.e., Avipoxvirus, Capripoxvirus, Cervidpoxvirus, Orthopoxvirus, Suipoxvirus, Yatapoxvirus, and one Entomopox genus- Betaentomopoxvirus, and some unclassified Entomopoxvirus are significantly rich in AT composition. Four other Chordopox genera- Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, and some unclassified Chordopoxvirus are dominated by the GC rich viruses. Poxviruses from these AT rich and GC rich genera preferred AT or GC ending codons owing to their respective nucleotide compositional bias. For example, viruses from AT rich Orthopoxvirus, or GC rich Parapoxvirus have evolved with mutually exclusive type codon preferences following their genus-specific nucleotide compositions. Additional factors like gene length and expression level also influenced their codon usage patterns to some extent in some Poxvirus genera. Evidences from correspondence analysis and cluster analysis on the extent of divergence in codon usage also support this genus specific evolution of Poxvirus codon usage. Analyzes suggest that most of the Poxviruses from different genera, have evolved in almost two different evolutionary trajectory in context of their nucleotide composition and codon usage.

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

    Science.gov (United States)

    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 ...

  1. Codon usage influences the local rate of translation elongation to regulate co-translational protein folding

    Science.gov (United States)

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

    2015-01-01

    Summary 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 rate of translation elongation, whereas non-optimal codons slow elognatioon. Codon usage also controls ribosome traffic on mRNA. These conclusions were further supported by ribosome profiling results in vitro and in vivo with template mRNAs designed to increase signal to noise. 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. Characterization of Variant Creutzfeldt-Jakob Disease Prions in Prion Protein-humanized Mice Carrying Distinct Codon 129 Genotypes*

    Science.gov (United States)

    Takeuchi, Atsuko; Kobayashi, Atsushi; Ironside, James W.; Mohri, Shirou; Kitamoto, Tetsuyuki

    2013-01-01

    To date, all clinical variant Creutzfeldt-Jakob disease (vCJD) patients are homozygous for methionine at polymorphic codon 129 (129M/M) of the prion protein (PrP) gene. However, the appearance of asymptomatic secondary vCJD infection in individuals with a PRNP codon 129 genotype other than M/M and transmission studies using animal models have raised the concern that all humans might be susceptible to vCJD prions, especially via secondary infection. To reevaluate this possibility and to analyze in detail the transmission properties of vCJD prions to transgenic animals carrying distinct codon 129 genotype, we performed intracerebral inoculation of vCJD prions to humanized knock-in mice carrying all possible codon 129 genotypes (129M/M, 129M/V, or 129V/V). All humanized knock-in mouse lines were susceptible to vCJD infection, although the attack rate gradually decreased from 129M/M to 129M/V and to 129V/V. The amount of PrP deposition including florid/amyloid plaques in the brain also gradually decreased from 129M/M to 129M/V and to 129V/V. The biochemical properties of protease-resistant abnormal PrP in the brain and transmissibility of these humanized mouse-passaged vCJD prions upon subpassage into knock-in mice expressing bovine PrP were not affected by the codon 129 genotype. These results indicate that individuals with the 129V/V genotype may be more susceptible to secondary vCJD infection than expected and may lack the neuropathological characteristics observed in vCJD patients with the 129M/M genotype. Besides the molecular typing of protease-resistant PrP in the brain, transmission studies using knock-in mice carrying bovine PrP may aid the differential diagnosis of secondary vCJD infection, especially in individuals with the 129V/V genotype. PMID:23792955

  3. Codon Y791F mutations in a large kindred: is prophylactic thyroidectomy always indicated?

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Vestergaard, Else Marie; Brockstedt, Helle

    2007-01-01

    : Eight members of a Danish family with the Y791F mutation participated. All gene carriers underwent pentagastrin testing, and measurements of serum calcitonin. In the index person, exons 10, 11, and 13-16 of the RET proto-oncogene were screened. In the rest of the individuals only exon 13 was analysed....... Mutation analysis was done by direct bidirectional sequencing of PCR products on an ABI 3100 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). RESULTS: The index person was screened genetically due to goitre at a young age. A total of 27 members of the family underwent genetic testing. Twelve...

  4. Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity

    Directory of Open Access Journals (Sweden)

    Ivaylo P. Ivanov

    2017-06-01

    Full Text Available Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs in its >700-nucleotide (nt 5′ leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5′ region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5′ conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro. In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression.

  5. Variability of Heart Rate in Primitive Horses and Their Relatives as an Indicator of Stress Level, Behavioural Conduct Towards Humans and Adaptation to Living in Wild

    Directory of Open Access Journals (Sweden)

    Pluta Michał

    2014-10-01

    Full Text Available The aim of the study was to evaluate the possibility of using heart rate (HR as a metric parameter that can be used for the characterisation of behaviour of primitive horses and their relatives, related to reactions to the stress resulting from the contact with humans and adaptation to living in various conditions, including natural environment. This characterisation served the authors to expand the knowledge of such behaviour of primitive horses, and to assess the impact of the environmental and genetic factors. Studies were conducted in three populations of horses: two herds of Polish Konik and one herd of Biłgoraj horses. The studies were performed between 1993 and 2010. They concerned the behaviour of horses during grooming - breeding procedures (hooves clearing, body measurements performed cyclically and the daily observations when HR was monitored continuously. HR results for the respective age categories, during particular grooming - breeding procedures and reserve observations indicate that Polish Konik horses, closely related to the primitive Tarpan breed, are genetically better adapted to living in conditions similar to the natural (reserve than the Biłgoraj horses. They show less stress symptoms, which are evidenced by HR values noted during inhabiting the natural environment.

  6. A novel mutation in the FGB: c.1105C>T turns the codon for amino acid Bβ Q339 into a stop codon causing hypofibrinogenemia.

    Science.gov (United States)

    Marchi, Rita; Brennan, Stephen; Meyer, Michael; Rojas, Héctor; Kanzler, Daniela; De Agrela, Marisela; Ruiz-Saez, Arlette

    2013-03-01

    Routine coagulation tests on a 14year-old male with frequent epistaxis showed a prolonged thrombin time together with diminished functional (162mg/dl) and gravimetric (122mg/dl) fibrinogen concentrations. His father showed similar aberrant results and sequencing of the three fibrinogen genes revealed a novel heterozygous nonsense mutation in the FGB gene c.1105C>T, which converts the codon for residue Bβ 339Q to stop, causing deletion of Bβ chain residues 339-461. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and RP-HPLC (reverse-phase high-pressure liquid chromatography) of purified fibrinogen showed only normal Aα, Bβ, and γ chains, indicating that molecules with the truncated 37,990Da β chain were not secreted into plasma. Functional analysis showed impaired fibrin polymerization, fibrin porosity, and elasticity compared to controls. By laser scanning confocal microscopy the patient's fibers were slightly thinner than normal. Electrospray ionization mass spectrometry (ESI MS) presented normal sialylation of the oligosaccharide chains, and liver function tests showed no evidence of liver dysfunction that might explain the functional abnormalities. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-07-01

    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. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells.

    Science.gov (United States)

    Zhao, Fangzhou; Yu, Chien-Hung; Liu, Yi

    2017-08-21

    Codon usage biases are found in all eukaryotic and prokaryotic genomes and have been proposed to regulate different aspects of translation process. Codon optimality has been shown to regulate translation elongation speed in fungal systems, but its effect on translation elongation speed in animal systems is not clear. In this study, we used a Drosophila cell-free translation system to directly compare the velocity of mRNA translation elongation. Our results demonstrate that optimal synonymous codons speed up translation elongation while non-optimal codons slow down translation. In addition, codon usage regulates ribosome movement and stalling on mRNA during translation. Finally, we show that codon usage affects protein structure and function in vitro and in Drosophila cells. Together, these results suggest that the effect of codon usage on translation elongation speed is a conserved mechanism from fungi to animals that can affect protein folding in eukaryotic organisms. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Directory of Open Access Journals (Sweden)

    Hoda Mirsafian

    2014-01-01

    Full Text Available 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.

  10. Versatile dual reporter gene systems for investigating stop codon readthrough in plants.

    Directory of Open Access Journals (Sweden)

    Nga T Lao

    2009-10-01

    Full Text Available Translation is most often terminated when a ribosome encounters the first in-frame stop codon (UAA, UAG or UGA in an mRNA. However, many viruses (and some cellular mRNAs contain "stop" codons that cause a proportion of ribosomes to terminate and others to incorporate an amino acid and continue to synthesize a "readthrough", or C-terminally extended, protein. This dynamic redefinition of codon meaning is dependent on specific sequence context.We describe two versatile dual reporter systems which facilitate investigation of stop codon readthrough in vivo in intact plants, and identification of the amino acid incorporated at the decoded stop codon. The first is based on the reporter enzymes NAN and GUS for which sensitive fluorogenic and histochemical substrates are available; the second on GST and GFP.We show that the NAN-GUS system can be used for direct in planta measurements of readthrough efficiency following transient expression of reporter constructs in leaves, and moreover, that the system is sufficiently sensitive to permit measurement of readthrough in stably transformed plants. We further show that the GST-GFP system can be used to affinity purify readthrough products for mass spectrometric analysis and provide the first definitive evidence that tyrosine alone is specified in vivo by a 'leaky' UAG codon, and tyrosine and tryptophan, respectively, at decoded UAA, and UGA codons in the Tobacco mosaic virus (TMV readthrough context.

  11. Comparative evolutionary genomics of Corynebacterium with special reference to codon and amino acid usage diversities.

    Science.gov (United States)

    Pal, Shilpee; Sarkar, Indrani; Roy, Ayan; Mohapatra, Pradeep K Das; Mondal, Keshab C; Sen, Arnab

    2018-02-01

    The present study has been aimed to the comparative analysis of high GC composition containing Corynebacterium genomes and their evolutionary study by exploring codon and amino acid usage patterns. Phylogenetic study by MLSA approach, indel analysis and BLAST matrix differentiated Corynebacterium species in pathogenic and non-pathogenic clusters. Correspondence analysis on synonymous codon usage reveals that, gene length, optimal codon frequencies and tRNA abundance affect the gene expression of Corynebacterium. Most of the optimal codons as well as translationally optimal codons are C ending i.e. RNY (R-purine, N-any nucleotide base, and Y-pyrimidine) and reveal translational selection pressure on codon bias of Corynebacterium. Amino acid usage is affected by hydrophobicity, aromaticity, protein energy cost, etc. Highly expressed genes followed the cost minimization hypothesis and are less diverged at their synonymous positions of codons. Functional analysis of core genes shows significant difference in pathogenic and non-pathogenic Corynebacterium. The study reveals close relationship between non-pathogenic and opportunistic pathogenic Corynebaterium as well as between molecular evolution and survival niches of the organism.

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

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    2016-08-01

    Full Text Available 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.

  13. Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.

    Directory of Open Access Journals (Sweden)

    Tarikul Huda Mazumder

    Full Text Available 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.

  14. ChloroMitoCU: Codon patterns across organelle genomes for functional genomics and evolutionary applications.

    Science.gov (United States)

    Sablok, Gaurav; Chen, Ting-Wen; Lee, Chi-Ching; Yang, Chi; Gan, Ruei-Chi; Wegrzyn, Jill L; Porta, Nicola L; Nayak, Kinshuk C; Huang, Po-Jung; Varotto, Claudio; Tang, Petrus

    2017-06-01

    Organelle genomes are widely thought to have arisen from reduction events involving cyanobacterial and archaeal genomes, in the case of chloroplasts, or α-proteobacterial genomes, in the case of mitochondria. Heterogeneity in base composition and codon preference has long been the subject of investigation of topics ranging from phylogenetic distortion to the design of overexpression cassettes for transgenic expression. From the overexpression point of view, it is critical to systematically analyze the codon usage patterns of the organelle genomes. In light of the importance of codon usage patterns in the development of hyper-expression organelle transgenics, we present ChloroMitoCU, the first-ever curated, web-based reference catalog of the codon usage patterns in organelle genomes. ChloroMitoCU contains the pre-compiled codon usage patterns of 328 chloroplast genomes (29,960 CDS) and 3,502 mitochondrial genomes (49,066 CDS), enabling genome-wide exploration and comparative analysis of codon usage patterns across species. ChloroMitoCU allows the phylogenetic comparison of codon usage patterns across organelle genomes, the prediction of codon usage patterns based on user-submitted transcripts or assembled organelle genes, and comparative analysis with the pre-compiled patterns across species of interest. ChloroMitoCU can increase our understanding of the biased patterns of codon usage in organelle genomes across multiple clades. ChloroMitoCU can be accessed at: http://chloromitocu.cgu.edu.tw/. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  15. Towards Reassignment of the Methionine Codon AUG to Two Different Noncanonical Amino Acids in Bacterial Translation

    Directory of Open Access Journals (Sweden)

    Alessandro De Simone

    2016-06-01

    Full Text Available Genetic encoding of noncanonical amino acids (ncAAs through sense codon reassignment is an efficient tool for expanding the chemical functionality of proteins. Incorporation of multiple ncAAs, however, is particularly challenging. This work describes the first attempts to reassign the sense methionine (Met codon AUG to two different ncAAs in bacterial protein translation. Escherichia coli methionyl-tRNA synthetase (MetRS charges two tRNAs with Met: tRNAfMet initiates protein synthesis (starting AUG codon, whereas elongator tRNAMet participates in protein elongation (internal AUG codon(s. Preliminary in vitro experiments show that these tRNAs can be charged with the Met analogues azidohomoalanine (Aha and ethionine (Eth by exploiting the different substrate specificities of EcMetRS and the heterologous MetRS / tRNAMet pair from the archaeon Sulfolobus acidocaldarius, respectively. Here, we explored whether this configuration would allow a differential decoding during in vivo protein initiation and elongation. First, we eliminated the elongator tRNAMet from a methionine auxotrophic E. coli strain, which was then equipped with a rescue plasmid harboring the heterologous pair. Although the imported pair was not fully orthogonal, it was possible to incorporate preferentially Eth at internal AUG codons in a model protein, suggesting that in vivo AUG codon reassignment is possible. To achieve full orthogonality during elongation, we imported the known orthogonal pair of Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS / tRNAPyl and devised a genetic selection system based on the suppression of an amber stop codon in an important glycolytic gene, pfkA, which restores enzyme functionality and normal cellular growth. Using an evolved PylRS able to accept Met analogues, it should be possible to reassign the AUG codon to two different ncAAs by using directed evolution. This work is licensed under a Creative Commons Attribution 4.0 International

  16. Codon usage bias and phylogenetic analysis of mitochondrial ND1 gene in pisces, aves, and mammals.

    Science.gov (United States)

    Uddin, Arif; Choudhury, Monisha Nath; Chakraborty, Supriyo

    2018-01-01

    The mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) gene is a subunit of the respiratory chain complex I and involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). To understand the pattern of compositional properties, codon usage and expression level of mitochondrial ND1 genes in pisces, aves, and mammals, we used bioinformatic approaches as no work was reported earlier. In this study, a perl script was used for calculating nucleotide contents and different codon usage bias parameters. The codon usage bias of MT-ND1 was low but the expression level was high as revealed from high ENC and CAI value. Correspondence analysis (COA) suggests that the pattern of codon usage for MT-ND1 gene is not same across species and that compositional constraint played an important role in codon usage pattern of this gene among pisces, aves, and mammals. From the regression equation of GC12 on GC3, it can be inferred that the natural selection might have played a dominant role while mutation pressure played a minor role in influencing the codon usage patterns. Further, ND1 gene has a discrepancy with cytochrome B (CYB) gene in preference of codons as evident from COA. The codon usage bias was low. It is influenced by nucleotide composition, natural selection, mutation pressure, length (number) of amino acids, and relative dinucleotide composition. This study helps in understanding the molecular biology, genetics, evolution of MT-ND1 gene, and also for designing a synthetic gene.

  17. Factors influencing codon usage of mitochondrial ND1 gene in pisces, aves and mammals.

    Science.gov (United States)

    Uddin, Arif; Choudhury, Monisha Nath; Chakraborty, Supriyo

    2017-11-01

    Animal mitochondrial genome harbours 13 protein coding genes which regulate the process of respiration. The mitochondrial NADH dehydrogenase 1 (MT-ND1) gene, one of the 13 protein-coding genes, encodes the NADH dehydrogenase 1 enzyme of the respiratory chain. Analysis of codon usage bias (CUB) acquires importance for better understanding of the molecular biology, new gene discovery, design of transgenes and gene evolution. The MT-ND1 gene seems to be a good candidate for analyzing codon usage pattern, since no work has yet been reported. Moreover, it is still not clear which factors significantly influence the codon usage pattern. In the present study, comparative analysis of codon usage pattern, expression level and influencing factors for MT-ND1 gene from 100 different species each of pisces, aves and mammals were used for CUB analysis. Our result suggests that the gene is AT rich in pisces, aves and mammals and most of the nucleotides significantly differ among them as revealed from t-test. CUB was not remarkable as reflected by high value of effective number of codons and it also significantly differs among pisces, aves and mammals. Although we found that CUB is mainly influenced by natural selection and mutation pressure for MT-ND1 gene as suggested by correlation and correspondence analysis but neutrality plot further revealed that natural selection played a major role and mutation pressure played a minor role in codon usage pattern. Additionally, t-test analysis showed that the MT-ND1 gene has a wide significant discrepancy in codon choices in pisces, aves and mammals. This study has contributed to boost our understanding about the mechanism of distribution of the codons and the factors that may influence the evolution of the MT-ND1 gene. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  18. Distribution of acI-Actinorhodopsin genes in Baltic Sea salinity gradients indicates adaptation of facultative freshwater photoheterotrophs to brackish waters.

    Science.gov (United States)

    Salka, Ivette; Wurzbacher, Christian; Garcia, Sarahi L; Labrenz, Matthias; Jürgens, Klaus; Grossart, Hans-Peter

    2014-02-01

    Knowledge on Actinobacteria rhodopsin gene (actR) diversity and spatial distribution is scarce. The Baltic Sea is characterized by strong salinity gradients leading to the coexistence of marine and freshwater bacteria and hence is an ideal study area to elucidate the dispersion and phylogenetic affiliation of actR in dependence on salinity. ActR DGGE fingerprints in summer 2008 revealed between 3 and 19 distinct bands within a salinity range of 2.4-27 PSU. Environmental actR clone sequences were obtained from stations distributed along the whole salinity gradient. Overall, 20 different actR sequence groups (operational taxonomic units) were found, with up to 11 different ones per station. Phylogenetically, the actR sequences were predominantly (80%) affiliated with freshwater acI-Actinobacteria whose 16S rRNA gene accounted for 2-33% of total 16S rRNA genes in both the Bothnian Sea and central Baltic Sea. However, at salinities above 14 PSU, acI-16S rRNA gene accounted for less than 1%. In contrast, the diversity of actR remained high. Changes in actR gene diversity were significantly correlated with salinity, oxygen, silica or abundance of Synechococcus sp. Our results demonstrate a wide distribution of freshwater actR along the Baltic Sea salinity gradient indicating that some freshwater Actinobacteria might have adapted to higher salinities. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  19. Codon sextets with leading role of serine create "ideal" symmetry classification scheme of the genetic code.

    Science.gov (United States)

    Rosandić, Marija; Paar, Vladimir

    2014-06-10

    The standard classification scheme of the genetic code is organized for alphabetic ordering of nucleotides. Here we introduce the new, "ideal" classification scheme in compact form, for the first time generated by codon sextets encoding Ser, Arg and Leu amino acids. The new scheme creates the known purine/pyrimidine, codon-anticodon, and amino/keto type symmetries and a novel A+U rich/C+G rich symmetry. This scheme is built from "leading" and "nonleading" groups of 32 codons each. In the ensuing 4 × 16 scheme, based on trinucleotide quadruplets, Ser has a central role as initial generator. Six codons encoding Ser and six encoding Arg extend continuously along a linear array in the "leading" group, and together with four of six Leu codons uniquely define construction of the "leading" group. The remaining two Leu codons enable construction of the "nonleading" group. The "ideal" genetic code suggests the evolution of genetic code with serine as an initiator. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Decoding mechanisms by which silent codon changes influence protein biogenesis and function.

    Science.gov (United States)

    Bali, Vedrana; Bebok, Zsuzsanna

    2015-07-01

    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. 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. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Codon 129 polymorphism of prion protein gene in is not a risk factor for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jerusa Smid

    2013-07-01

    Full Text Available Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD. Objective To describe the association between codon 129 polymorphisms and AD. Methods We investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE were evaluated. Results Codon 129 genotype distribution in AD 45.5% methionine (MM, 42.2% methionine valine (MV, 12.1% valine (VV; and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05. There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups. Conclusion Codon 129 polymorphism is not a risk factor for AD in Brazilian patients.

  2. Biochemical features of genetic Creutzfeldt-Jakob disease with valine-to-isoleucine substitution at codon 180 on the prion protein gene.

    Science.gov (United States)

    Ito, Yoko; Sanjo, Nobuo; Hizume, Masaki; Kobayashi, Atsushi; Ohgami, Tetsuya; Satoh, Katsuya; Hamaguchi, Tsuyoshi; Yamada, Masahito; Kitamoto, Tetsuyuki; Mizusawa, Hidehiro; Yokota, Takanori

    2018-02-19

    Valine-to-isoleucine substitution at codon 180 of the prion protein gene is only observed in patients with Creutzfeldt-Jakob disease and accounts for approximately half of all cases of genetic prion disease in Japan. In the present study, we investigated the biochemical characteristics of valine-to-isoleucine substitution at codon 180 in the prion protein gene, using samples obtained from the autopsied brains of seven patients with genetic Creutzfeldt-Jakob disease exhibiting this mutation (diagnoses confirmed via neuropathological examination). Among these patients, we observed an absence of diglycosylated and monoglycosylated forms of PrP res at codon 181. Our findings further indicated that the abnormal prion proteins were composed of at least three components, although smaller carboxyl-terminal fragments were predominant. Western blot analyses revealed large amounts of PrP res in the cerebral neocortices, where neuropathological examination revealed marked spongiosis. Relatively smaller amounts of PrP res were detected in the hippocampus, where milder spongiosis was observed, than in the cerebral neocortex. These findings indicate that abnormal prion proteins in the neocortex are associated with severe toxicity, resulting in severe spongiosis. Our findings further indicate that the valine-to-isoleucine substitution is not a polymorphism, but rather an authentic pathogenic mutation associated with specific biochemical characteristics that differ from those observed in sporadic Creutzfeldt-Jakob disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Absolute in vivo translation rates of individual codons in Escherichia coli: The two glutamic acid codons GAA and GAG are translated with a threefold difference in rate

    DEFF Research Database (Denmark)

    Sørensen, M.A.; Pedersen, Steen

    1991-01-01

    We have determined the absolute translation rates for four individual codons in Escherichia coli. We used our previously described system for direct measurements of in vivo translation rates using small, in-frame inserts in the lacZ gene. The inserts consisted of multiple synthetic 30 base-pair D...

  4. Start codon targeted (scot polymorphism reveals genetic diversity in european old maize (zea mays l. Genotypes

    Directory of Open Access Journals (Sweden)

    Martin Vivodík

    2016-11-01

    Full Text Available Maize (Zea mays L. is one of the world's most important crop plants following wheat and rice, which provides staple food to large number of human population in the world. It is cultivated in a wider range of environments than wheat and rice because of its greater adaptability. Molecular characterization is frequently used by maize breeders as an alternative method for selecting more promising genotypes and reducing the cost and time needed to develop hybrid combinations. In the present investigation 40 genotypes of maize from Czechoslovakia, Hungary, Poland, Union of Soviet Socialist Republics, Slovakia and Yugoslavia were analysed using 20 Start codon targeted (SCoT markers. These primers produced total 114 fragments across 40 maize genotypes, of which 86 (76.43% were polymorphic with an average of 4.30 polymorphic fragments per primer and number of amplified fragments ranged from 2 (SCoT 45 to 8 (SCoT 28 and SCoT 63. The polymorphic information content (PIC value ranged from 0.374 (ScoT 45 to 0.846 (SCoT 28 with an average of 0.739. The dendrogram based on hierarchical cluster analysis using UPGMA algorithm was prepared. The hierarchical cluster analysis showed that the maize genotypes were divided into two main clusters. Unique maize genotype (cluster 1, Zuta Brzica, originating from Yugoslavia separated from others. Cluster 2 was divided into two main clusters (2a and 2b. Subcluster 2a contained one Yugoslavian genotype Juhoslavanska and subcluster 2b was divided in two subclusters 2ba and 2bb. The present study shows effectiveness of employing SCoT markers in analysis of maize, and would be useful for further studies in population genetics, conservation genetics and genotypes improvement.

  5. Mapping the Plasticity of the E. coli Genetic Code with Orthogonal Pair Directed Sense Codon Reassignment.

    Science.gov (United States)

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

    2018-04-18

    The relative quantitative importance of the factors that determine the fidelity of translation is largely unknown, which makes predicting the extent to which the degeneracy of the genetic code can be broken challenging. Our strategy of using orthogonal tRNA/aminoacyl tRNA synthetase pairs to precisely direct the incorporation of a single amino acid in response to individual sense and nonsense codons provides a suite of related data with which to examine the plasticity of the code. Each directed sense codon reassignment measurement is an in vivo competition experiment between the introduced orthogonal translation machinery and the natural machinery in E. coli. This report discusses 20 new, related genetic codes, in which a targeted E. coli wobble codon is reassigned to tyrosine utilizing the orthogonal tyrosine tRNA/aminoacyl tRNA synthetase pair from Methanocaldococcus jannaschii. One at a time, reassignment of each targeted sense codon to tyrosine is quantified in cells by measuring the fluorescence of GFP variants in which the essential tyrosine residue is encoded by a non-tyrosine codon. Significantly, every wobble codon analyzed may be partially reassigned with efficiencies ranging from 0.8% to 41%. The accumulation of the suite of data enables a qualitative dissection of the relative importance of the factors affecting the fidelity of translation. While some correlation was observed between sense codon reassignment and either competing endogenous tRNA abundance or changes in aminoacylation efficiency of the altered orthogonal system, no single factor appears to predominately drive translational fidelity. Evaluation of relative cellular fitness in each of the 20 quantitatively-characterized proteome-wide tyrosine substitution systems suggests that at a systems level, E. coli is robust to missense mutations.

  6. GC-Content of Synonymous Codons Profoundly Influences Amino Acid Usage.

    Science.gov (United States)

    Li, Jing; Zhou, Jun; Wu, Ying; Yang, Sihai; Tian, Dacheng

    2015-08-06

    Amino acids typically are encoded by multiple synonymous codons that are not used with the same frequency. Codon usage bias has drawn considerable attention, and several explanations have been offered, including variation in GC-content between species. Focusing on a simple parameter-combined GC proportion of all the synonymous codons for a particular amino acid, termed GCsyn-we try to deepen our understanding of the relationship between GC-content and amino acid/codon usage in more details. We analyzed 65 widely distributed representative species and found a close association between GCsyn, GC-content, and amino acids usage. The overall usages of the four amino acids with the greatest GCsyn and the five amino acids with the lowest GCsyn both vary with the regional GC-content, whereas the usage of the remaining 11 amino acids with intermediate GCsyn is less variable. More interesting, we discovered that codon usage frequencies are nearly constant in regions with similar GC-content. We further quantified the effects of regional GC-content variation (low to high) on amino acid usage and found that GC-content determines the usage variation of amino acids, especially those with extremely high GCsyn, which accounts for 76.7% of the changed GC-content for those regions. Our results suggest that GCsyn correlates with GC-content and has impact on codon/amino acid usage. These findings suggest a novel approach to understanding the role of codon and amino acid usage in shaping genomic architecture and evolutionary patterns of organisms. Copyright © 2015 Li et al.

  7. ADAPTATION ET VALIDATION D’UN INDICE POISSON (FBI POUR L’ÉVALUATION DE LA QUALITÉ BIOLOGIQUE DES COURS D’EAU FRANÇAIS.

    Directory of Open Access Journals (Sweden)

    OBERDORFF T.

    2002-04-01

    Full Text Available La récente Directive Cadre sur l’Eau (DCE demande aux états membres de la communauté européenne la préservation et la restauration de l’état écologique des écosystèmes aquatiques au travers de leurs composantes chimiques et biologiques. Satisfaire cette demande nécessite de disposer d’indicateurs biologiques capables d’apporter une information pertinente sur l’état de santé de ces écosystèmes. Ces indicateurs doivent être scientifiquement valides, efficaces, rapides à mettre en œuvre et applicables à différentes régions géographiques. Parmi les indicateurs potentiels, les peuplements de poissons peuvent apporter une information originale en raison de la capacité qu’ont ces organismes à intégrer la variabilité environnementale à différentes échelles spatiales. Dans ce contexte, les Agences de l’Eau, le Ministère de l’Environnement et le Conseil Supérieur de la Pêche ont lancé conjointement un programme national d’adaptation d’un indice biotique fondé sur les peuplements poissons applicable à l’ensemble du réseau hydrographique. Adapter ce type d’indice à une échelle spatiale telle que le réseau hydrographique national nécessite la prise en compte des facteurs environnementaux majeurs responsables des variations des peuplements en conditions naturelles. La démarche adoptée pour l’établissement de l’indice s’établit comme suit. Dans un premier temps et en utilisant un jeu de donnée de 650 stations de référence réparties de manière homogène sur l’ensemble du réseau hydrographique national, la probabilité d’occurrence sur une station de 34 espèces les plus communes de nos cours d’eau a été modélisée en fonction d’un certain nombre de variables environnementales locales et régionales (i.e. position de la station sur le gradient longitudinal, altitude, vitesse moyenne du courant, conditions thermiques, appartenance à une unité hydrologique. Dans un deuxi

  8. Genomic composition factors affect codon usage in porcine genome

    African Journals Online (AJOL)

    j.khobondo

    2015-01-28

    Jan 28, 2015 ... expression of target genes in vivo or in vitro and improve the accuracy of gene prediction from genomic sequences thus maximizing ... These biological breakthroughs revealed the importance of studying the degeneracy of ... diversity, gene expression and evolution, and adaptation to micro environment.

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

    Science.gov (United States)

    Boël, Grégory; Wong, Kam-Ho; Su, Min; Luff, Jon; Valecha, Mayank; Everett, John K.; Acton, Thomas B.; Xiao, Rong; Montelione, Gaetano T.; Aalberts, Daniel P.; Hunt, John F.

    2016-01-01

    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 analyze 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

  10. An overabundance of phase 0 introns immediately after the start codon in eukaryotic genes

    Directory of Open Access Journals (Sweden)

    Wernersson Rasmus

    2006-10-01

    Full Text Available Abstract Background A knowledge of the positions of introns in eukaryotic genes is important for understanding the evolution of introns. Despite this, there has been relatively little focus on the distribution of intron positions in genes. Results In proteins with signal peptides, there is an overabundance of phase 1 introns around the region of the signal peptide cleavage site. This has been described before. But in proteins without signal peptides, a novel phenomenon is observed: There is a sharp peak of phase 0 intron positions immediately following the start codon, i.e. between codons 1 and 2. This effect is seen in a wide range of eukaryotes: Vertebrates, arthropods, fungi, and flowering plants. Proteins carrying this start codon intron are found to comprise a special class of relatively short, lysine-rich and conserved proteins with an overrepresentation of ribosomal proteins. In addition, there is a peak of phase 0 introns at position 5 in Drosophila genes with signal peptides, predominantly representing cuticle proteins. Conclusion There is an overabundance of phase 0 introns immediately after the start codon in eukaryotic genes, which has been described before only for human ribosomal proteins. We give a detailed description of these start codon introns and the proteins that contain them.

  11. An overabundance of phase 0 introns immediately after the start codon in eukaryotic genes.

    Science.gov (United States)

    Nielsen, Henrik; Wernersson, Rasmus

    2006-10-11

    A knowledge of the positions of introns in eukaryotic genes is important for understanding the evolution of introns. Despite this, there has been relatively little focus on the distribution of intron positions in genes. In proteins with signal peptides, there is an overabundance of phase 1 introns around the region of the signal peptide cleavage site. This has been described before. But in proteins without signal peptides, a novel phenomenon is observed: There is a sharp peak of phase 0 intron positions immediately following the start codon, i.e. between codons 1 and 2. This effect is seen in a wide range of eukaryotes: Vertebrates, arthropods, fungi, and flowering plants. Proteins carrying this start codon intron are found to comprise a special class of relatively short, lysine-rich and conserved proteins with an overrepresentation of ribosomal proteins. In addition, there is a peak of phase 0 introns at position 5 in Drosophila genes with signal peptides, predominantly representing cuticle proteins. There is an overabundance of phase 0 introns immediately after the start codon in eukaryotic genes, which has been described before only for human ribosomal proteins. We give a detailed description of these start codon introns and the proteins that contain them.

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

    Directory of Open Access Journals (Sweden)

    Indu S Panicker

    Full Text Available 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.

  13. %MinMax: A versatile tool for calculating and comparing synonymous codon usage and its impact on protein folding.

    Science.gov (United States)

    Rodriguez, Anabel; Wright, Gabriel; Emrich, Scott; Clark, Patricia L

    2018-01-01

    Most amino acids can be encoded by more than one synonymous codon, but these are rarely used with equal frequency. In many coding sequences the usage patterns of rare versus common synonymous codons is nonrandom and under selection. Moreover, synonymous substitutions that alter these patterns can have a substantial impact on the folding efficiency of the encoded protein. This has ignited broad interest in exploring synonymous codon usage patterns. For many protein chemists, biophysicists and structural biologists, the primary motivation for codon analysis is identifying and preserving usage patterns most likely to impact high-yield production of functional proteins. Here we describe the core functions and new features of %MinMax, a codon usage calculator freely available as a web-based portal and downloadable script (http://www.codons.org). %MinMax evaluates the relative usage frequencies of the synonymous codons used to encode a protein sequence of interest and compares these results to a rigorous null model. Crucially, for analyzing codon usage in common host organisms %MinMax requires only the coding sequence as input; with a user-input codon frequency table, %MinMax can be used to evaluate synonymous codon usage patterns for any coding sequence from any fully sequenced genome. %MinMax makes no assumptions regarding the impact of transfer ribonucleic acid concentrations or other molecular-level interactions on translation rates, yet its output is sufficient to predict the effects of synonymous codon substitutions on cotranslational folding mechanisms. A simple calculation included within %MinMax can be used to harmonize codon usage frequencies for heterologous gene expression. © 2017 The Protein Society.

  14. Adaptation of the Quality Indicator for Rehabilitative Care (QuIRC) for use in mental health supported accommodation services (QuIRC-SA).

    Science.gov (United States)

    Killaspy, Helen; White, Sarah; Dowling, Sarah; Krotofil, Joanna; McPherson, Peter; Sandhu, Sima; Arbuthnott, Maurice; Curtis, Sarah; Leavey, Gerard; Priebe, Stefan; Shepherd, Geoff; King, Michael

    2016-04-14

    No standardised tools for assessing the quality of specialist mental health supported accommodation services exist. To address this, we adapted the Quality Indicator for Rehabilitative care-QuIRC-that was originally developed to assess the quality of longer term inpatient and community based mental health facilities. The QuIRC, which is completed by the service manager and gives ratings of seven domains of care, has good psychometric properties. Focus groups with staff of the three main types of supported accommodation in the UK (residential care, supported housing and floating outreach services) were carried out to identify potential amendments to the QuIRC. Additional advice was gained from consultation with three expert panels, two of which comprised service users with lived experience of mental health and supported accommodation services. The amended QuIRC (QuIRC-SA) was piloted with a manager of each of the three service types. Item response variance, inter-rater reliability and internal consistency were assessed in a random sample of 52 services. Factorial structure and discriminant validity were assessed in a larger random sample of 87 services. The QuIRC-SA comprised 143 items of which only 18 items showed a narrow range of response and five items had poor inter-rater reliability. The tool showed good discriminant validity, with supported housing services generally scoring higher than the other two types of supported accommodation on most domains. Exploratory factor analysis showed that the QuIRC-SA items loaded onto the domains to which they had been allocated. The QuIRC-SA is the first standardised tool for quality assessment of specialist mental health supported accommodation services. Its psychometric properties mean that it has potential for use in research as well as audit and quality improvement programmes. A web based application is being developed to make it more accessible which will produce a printable report for the service manager about the

  15. [The hyperiricosuria as an indicator of derangement of biologic functions of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension].

    Science.gov (United States)

    Titov, V N; Oshchepkova, E V; Dmitriev, V A; Gushchina, O V; Shiriaeva, Iu K; Iashin, A Ia

    2012-04-01

    During millions years in all animals allantoine (oxidized by uricase uric acid) was catabolite of purines and ascorbic acid was an acceptor of active forms of oxygen. The proximal tubules of nephron reabsorbed the trace amounts of uric acid Then during phylogenesis the primates had a mutation of ascorbic acid gen minus. Later on occurred a second spontaneous mutation and uricase gen minus and uric acid became catabolites of purines. In absence of ascorbic acid synthesis ions of urates became a major capturers of active forms of oxygen and all uric acid as before underwent the reabsorption. Later the carriers were formed which began in epithelium of proximal tubules to secrete all uric acid into urine. At every incident of "littering" of intercellular medium with endogenic flogogens (impairment of biologic function of endoecology) under compensatory development of biologic reaction of inflammation the need in inactivation of active forms of oxygen increases. Hence later on in phylogenesis one more stage was formed--post secretory reabsorption of uric acid In the biologic reaction of inflammation epithelium of proximal tubules initiates retentional hyperiricosuria. The general antioxidant activity of human blood plasma in 60% is presented by urates' ions. The excretion of uric acid includes 4 stages: filtration, full reabsorption, secretion and post secretory reabsorption. In phylogenesis these stages formed in sequence. The mild hyperiricosuria is most frequently considered as a non-specific indicator of activation of biologic reaction of inflammation. The productive hyperiricosuria develops more infrequently under surplus of meat food and cytolysis syndrome (intensification of cell loss in vivo). Under concentration of uric acid more than 400 mkmol/l part of urates circulates in intercellular medium in the form of crystals. The microcrystals of uric acid (biologic "litter") initiate the syndrome of systemic inflammatory response as an endogenic flogogen

  16. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus.

    Science.gov (United States)

    Kamath, Pauline L; Getz, Wayne M

    2011-05-18

    Major Histocompatibility Complex (MHC) genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA), DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli). We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS) averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN codon models allowed for variable rates of selection across codon sites at both loci and, at the DQA, supported the hypothesis of positive selection acting on specific sites. Observations of elevated genetic diversity and trans-species polymorphisms supported the conclusion that balancing selection may be acting on these loci. Furthermore, at the DQA, positive selection was occurring at antigen binding sites, suggesting that a few

  17. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus

    Directory of Open Access Journals (Sweden)

    Getz Wayne M

    2011-05-01

    Full Text Available Abstract Background Major Histocompatibility Complex (MHC genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. Results We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA, DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli. We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN dS. However, the most likely evolutionary codon models allowed for variable rates of selection across codon sites at both loci and, at the DQA, supported the hypothesis of positive selection acting on specific sites. Conclusions Observations of elevated genetic diversity and trans-species polymorphisms supported the conclusion that balancing selection may be acting on these loci. Furthermore, at the DQA, positive selection was

  18. Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins

    Science.gov (United States)

    Tang, Nicholas C.; Chilkoti, Ashutosh

    2016-04-01

    Most genes are synthesized using seamless assembly methods that rely on the polymerase chain reaction (PCR). However, PCR of genes encoding repetitive proteins either fails or generates nonspecific products. Motivated by the need to efficiently generate new protein polymers through high-throughput gene synthesis, here we report a codon-scrambling algorithm that enables the PCR-based gene synthesis of repetitive proteins by exploiting the codon redundancy of amino acids and finding the least-repetitive synonymous gene sequence. We also show that the codon-scrambling problem is analogous to the well-known travelling salesman problem, and obtain an exact solution to it by using De Bruijn graphs and a modern mixed integer linear programme solver. As experimental proof of the utility of this approach, we use it to optimize the synthetic genes for 19 repetitive proteins, and show that the gene fragments are amenable to PCR-based gene assembly and recombinant expression.

  19. Rare codons effect on expression of recombinant gene cassette in Escherichia coli BL21(DE3

    Directory of Open Access Journals (Sweden)

    Aghil Esmaeili-Bandboni

    2017-11-01

    Full Text Available Objective: To demonstrate the sensitivity of expression of fusion genes to existence of a large number of rare codons in recombinant gene sequenced. Methods: Primers for amplification of cholera toxin B, Shiga toxin B and gfp genes were designed by Primer3 software and synthesized. All of these 3 genes were cloned. Then the genes were fused together by restriction sites and enzymatic method. Two linkers were used as a flexible bridge in connection of these genes. Results: Cloning and fusion of cholera toxin B, Shiga toxin B and gfp genes were done correctly. After that, expression of the recombinant gene construction was surveyed. Conclusions: According to what was seen, because of the accumulation of 12 rare codons of Shiga toxin B and 19 rare codons of cholera toxin B in this gene cassette, the expression of the recombinant gene cassette, in Escherichia coli BL21, failed.

  20. Translational Selection for Speed Is Not Sufficient to Explain Variation in Bacterial Codon Usage Bias

    Science.gov (United States)

    2018-01-01

    Abstract Increasing growth rate across bacteria strengthens selection for faster translation, concomitantly increasing the total number of tRNA genes and codon usage bias (CUB: enrichment of specific synonymous codons in highly expressed genes). Typically, enriched codons are translated by tRNAs with higher gene copy numbers (GCN). A model of tRNA–CUB coevolution based on fast growth-associated selection on translational speed recapitulates these patterns. A key untested implication of the coevolution model is that translational selection should favor higher tRNA GCN for more frequently used amino acids, potentially weakening the effect of growth-associated selection on CUB. Surprisingly, we find that CUB saturates with increasing growth rate across γ-proteobacteria, even as the number of tRNA genes continues to increase. As predicted, amino acid-specific tRNA GCN is positively correlated with the usage of corresponding amino acids, but there is no correlation between growth rate associated changes in CUB and amino acid usage. Instead, we find that some amino acids—cysteine and those in the NNA/G codon family—show weak CUB that does not increase with growth rate, despite large variation in the corresponding tRNA GCN. We suggest that amino acid-specific variation in CUB is not explained by tRNA GCN because GCN does not influence the difference between translation times of synonymous codons as expected. Thus, selection on translational speed alone cannot fully explain quantitative variation in overall or amino acid-specific CUB, suggesting a significant role for other functional constraints and amino acid-specific codon features. PMID:29385509

  1. Nature-based solutions to climate change mitigation and adaptation in urban areas: Perspectives on indicators, knowledge gaps, barriers, and opportunities for action

    NARCIS (Netherlands)

    N. Kabisch (Nadja); N. Frantzeskaki (Niki); S. Pauleit (Stephan); Naumann, S. (Sandra); Davis, M. (McKenna); M. Artmann (Martina); D. Haase (Dagmar); Knapp, S. (Sonja); Korn, H. (Horst); Stadler, J. (Jutta); Zaunberger, K. (Karin); Bonn, A. (Aletta)

    2016-01-01

    textabstractNature-based solutions promoting green and blue urban areas have significant potential to decrease the vulnerability and enhance the resilience of cities in light of climatic change. They can thereby help to mitigate climate change-induced impacts and serve as proactive adaptation

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

    OpenAIRE

    Shah, Premal; Gilchrist, Michael A.

    2010-01-01

    Despite the fact that tRNA abundances are thought to play a major role in determining translation error rates, their distribution across the genetic code and the resulting implications have received little attention. In general, studies of codon usage bias (CUB) assume that codons with higher tRNA abundance have lower missense error rates. Using a model of protein translation based on tRNA competition and intra-ribosomal kinetics, we show that this assumption can be violated when tRNA abundan...

  3. THE INFLUENCE OF ISOLATED FABULATING FROM SMOKING OF TOBACCO ON THE INDICATORS OF FUNCTIONAL ADAPTATION FOR MILITARY SERVICEMENTS WITH PRECEDING UNDERGROUND WORK IN THE COAL MINE

    Directory of Open Access Journals (Sweden)

    Дмитрий Владимирович Чуркин

    2017-10-01

    Conclusions. It is necessary to use drugs and biologically active additives from servicemen with a previous experience of underground work in the coal mine that refused to smoke tobacco during the first 6 months in order to optimize the cardio-respiratory complex parameters and the basic energy exchange system, which will make it possible to form an adaptation reserve, which will allow To reduce morbidity and the growth of military-professional efficiency.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

    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.

  6. Maximum likelihood estimation of ancestral codon usage bias parameters in Drosophila

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Bauer DuMont, Vanessa L; Hubisz, Melissa J

    2007-01-01

    : the selection coefficient for optimal codon usage (S), allowing joint maximum likelihood estimation of S and the dN/dS ratio. We apply the method to previously published data from Drosophila melanogaster, Drosophila simulans, and Drosophila yakuba and show, in accordance with previous results, that the D...

  7. New LIC vectors for production of proteins from genes containing rare codons.

    Science.gov (United States)

    Eschenfeldt, William H; Makowska-Grzyska, Magdalena; Stols, Lucy; Donnelly, Mark I; Jedrzejczak, Robert; Joachimiak, Andrzej

    2013-12-01

    In the effort to produce proteins coded by diverse genomes, structural genomics projects often must express genes containing codons that are rare in the production strain. To address this problem, genes expressing tRNAs corresponding to those codons are typically coexpressed from a second plasmid in the host strain, or from genes incorporated into production plasmids. Here we describe the modification of a series of LIC pMCSG vectors currently used in the high-throughput (HTP) production of proteins to include crucial tRNA genes covering rare codons for Arg (AGG/AGA) and Ile (AUA). We also present variants of these new vectors that allow analysis of ligand binding or co-expression of multiple proteins introduced through two independent LIC steps. Additionally, to accommodate the cloning of multiple large proteins, the size of the plasmids was reduced by approximately one kilobase through the removal of non-essential DNA from the base vector. Production of proteins from core vectors of this series validated the desired enhanced capabilities: higher yields of proteins expressed from genes with rare codons occurred in most cases, biotinylated derivatives enabled detailed automated ligand binding analysis, and multiple proteins introduced by dual LIC cloning were expressed successfully and in near balanced stoichiometry, allowing tandem purification of interacting proteins.

  8. Unassigned Codons, Nonsense Suppression, and Anticodon Modifications in the Evolution of the Genetic Code

    NARCIS (Netherlands)

    P.T.S. van der Gulik (Peter); W.D. Hoff (Wouter)

    2011-01-01

    htmlabstractThe origin of the genetic code is a central open problem regarding the early evolution of life. Here, we consider two undeveloped but important aspects of possible scenarios for the evolutionary pathway of the translation machinery: the role of unassigned codons in early stages

  9. Tuning protein expression using synonymous codon libraries targeted to the 5' mRNA coding region

    DEFF Research Database (Denmark)

    Goltermann, Lise; Borch Jensen, Martin; Bentin, Thomas

    2011-01-01

    intermediate expression levels of green fluorescent protein in Escherichia coli. At least in one case, no apparent effect on protein stability was observed, pointing to RNA level effects as the principal reason for the observed expression differences. Targeting a synonymous codon library to the 5' coding...

  10. The p53 codon 72 polymorphism and association to prostate cancer ...

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... Tp53 is an important tumor suppressor gene, which induces cell growth arrest or apoptosis when subjected to cytotoxic ... Key words: Prostate cancer, suppressor gene (p53) codon 72, polymorphism, Iran. INTRODUCTION ..... 72 Polymorphism in Basal Cell Carcinoma of the Skin. Pathol. Oncol. Res. 12(1): ...

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

    Directory of Open Access Journals (Sweden)

    Christopher D Johnston

    2014-09-01

    Full Text Available 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 two MAP genes (MAP2121c and MAP3733c can enhance the heterologous expression of two antigens (MMP and MptD respectively, analogous to the form to which they are 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, codon optimised MptD displayed the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adhered with 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.

  12. Nucleotide composition of the Zika virus RNA genome and its codon usage

    NARCIS (Netherlands)

    van Hemert, Formijn; Berkhout, Ben

    2016-01-01

    RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and

  13. Thrombosis in Hb Taybe [codons 38/39 (-ACC) (α1)

    DEFF Research Database (Denmark)

    Juul, Maja Bech; Vestergaard, Hanne; Petersen, Jesper

    2012-01-01

    Hb Taybe is a highly unstable hemoglobin (Hb) variant caused by a 3 bp deletion at codons 38/39 (-ACC) on the α1-globin gene. We report for the first time, a patient with a compound heterozygosity for Hb Taybe and a 5 bp deletion at the splice donor site of IVS-I on the α2-globin gene and ischemic...

  14. Non-parent of Origin Expression of Numerous Effector Genes Indicates a Role of Gene Regulation in Host Adaption of the Hybrid Triticale Powdery Mildew Pathogen

    Science.gov (United States)

    Praz, Coraline R.; Menardo, Fabrizio; Robinson, Mark D.; Müller, Marion C.; Wicker, Thomas; Bourras, Salim; Keller, Beat

    2018-01-01

    Powdery mildew is an important disease of cereals. It is caused by one species, Blumeria graminis, which is divided into formae speciales each of which is highly specialized to one host. Recently, a new form capable of growing on triticale (B.g. triticale) has emerged through hybridization between wheat and rye mildews (B.g. tritici and B.g. secalis, respectively). In this work, we used RNA sequencing to study the molecular basis of host adaptation in B.g. triticale. We analyzed gene expression in three B.g. tritici isolates, two B.g. secalis isolates and two B.g. triticale isolates and identified a core set of putative effector genes that are highly expressed in all formae speciales. We also found that the genes differentially expressed between isolates of the same form as well as between different formae speciales were enriched in putative effectors. Their coding genes belong to several families including some which contain known members of mildew avirulence (Avr) and suppressor (Svr) genes. Based on these findings we propose that effectors play an important role in host adaptation that is mechanistically based on Avr-Resistance gene-Svr interactions. We also found that gene expression in the B.g. triticale hybrid is mostly conserved with the parent-of-origin, but some genes inherited from B.g. tritici showed a B.g. secalis-like expression. Finally, we identified 11 unambiguous cases of putative effector genes with hybrid-specific, non-parent of origin gene expression, and we propose that they are possible determinants of host specialization in triticale mildew. These data suggest that altered expression of multiple effector genes, in particular Avr and Svr related factors, might play a role in mildew host adaptation based on hybridization. PMID:29441081

  15. Non-parent of Origin Expression of Numerous Effector Genes Indicates a Role of Gene Regulation in Host Adaption of the Hybrid Triticale Powdery Mildew Pathogen

    Directory of Open Access Journals (Sweden)

    Coraline R. Praz

    2018-01-01

    Full Text Available Powdery mildew is an important disease of cereals. It is caused by one species, Blumeria graminis, which is divided into formae speciales each of which is highly specialized to one host. Recently, a new form capable of growing on triticale (B.g. triticale has emerged through hybridization between wheat and rye mildews (B.g. tritici and B.g. secalis, respectively. In this work, we used RNA sequencing to study the molecular basis of host adaptation in B.g. triticale. We analyzed gene expression in three B.g. tritici isolates, two B.g. secalis isolates and two B.g. triticale isolates and identified a core set of putative effector genes that are highly expressed in all formae speciales. We also found that the genes differentially expressed between isolates of the same form as well as between different formae speciales were enriched in putative effectors. Their coding genes belong to several families including some which contain known members of mildew avirulence (Avr and suppressor (Svr genes. Based on these findings we propose that effectors play an important role in host adaptation that is mechanistically based on Avr-Resistance gene-Svr interactions. We also found that gene expression in the B.g. triticale hybrid is mostly conserved with the parent-of-origin, but some genes inherited from B.g. tritici showed a B.g. secalis-like expression. Finally, we identified 11 unambiguous cases of putative effector genes with hybrid-specific, non-parent of origin gene expression, and we propose that they are possible determinants of host specialization in triticale mildew. These data suggest that altered expression of multiple effector genes, in particular Avr and Svr related factors, might play a role in mildew host adaptation based on hybridization.

  16. p53 gene mutations and codon 72 polymorphism in ovarian carcinoma patients from Serbia.

    Science.gov (United States)

    Malisic, E; Jankovic, R; Slavkovic, D; Milovic-Kovacevic, M; Radulovic, S

    2010-01-01

    Ovarian cancer is the leading cause of death from gynecological malignancies. The early stages of this disease are asymptomatic and more than 75% of the cases are diagnosed with regional or distant metastases. p53 gene is frequently mutated in some histological subtypes of ovarian carcinomas. The role of p53 mutations and polymorphic variant of codon 72 in the prognosis of disease is still unclear. The aim of this study was to determine the frequency of p53 mutations and polymorphic variants of codon 72 among ovarian carcinoma patients and to correlate them with clinicopathological characteristics of disease. 54 ovarian carcinoma patients were included in the study. DNA was isolated from tumor tissue by the salting- out method. p53 mutations in exons 4-8 were detected by PCR-SSCP (polymerase chain reaction - single-stranded conformational polymorphism) electrophoresis. Codon 72 polymorphism was assessed by RFLP (restriction fragment-length polymorphism) method. p53 mutations were present in 11 out of 54 patients (20.4%). Twenty-four patients (44.4%) exhibited Arg/ Arg, 24 patients (44.4%) Arg/Pro and 6 patients (11.2%) Pro/ Pro genotype of 72 codon polymorphism. Correlations between p53 mutations and various clinicopathological characteristics were not found. However, we observed that the frequency of Pro/Pro genotype was increasing with higher histological grade as well as in advanced compared to localized disease, but without statistical significance. Distribution of p53 gene mutations between Pro/Pro genotype and Arg/Pro plus Arg/Arg genotypes was not statistically significant. Our study suggests that Pro/Pro genotype of 72 codon polymorphism could be an independent prognostic marker in ovarian carcinomas.

  17. Phylogenetic dependency networks: inferring patterns of CTL escape and codon covariation in HIV-1 Gag.

    Directory of Open Access Journals (Sweden)

    Jonathan M Carlson

    2008-11-01

    Full Text Available HIV avoids elimination by cytotoxic T-lymphocytes (CTLs through the evolution of escape mutations. Although there is mounting evidence that these escape pathways are broadly consistent among individuals with similar human leukocyte antigen (HLA class I alleles, previous population-based studies have been limited by the inability to simultaneously account for HIV codon covariation, linkage disequilibrium among HLA alleles, and the confounding effects of HIV phylogeny when attempting to identify HLA-associated viral evolution. We have developed a statistical model of evolution, called a phylogenetic dependency network, that accounts for these three sources of confounding and identifies the primary sources of selection pressure acting on each HIV codon. Using synthetic data, we demonstrate the utility of this approach for identifying sites of HLA-mediated selection pressure and codon evolution as well as the deleterious effects of failing to account for all three sources of confounding. We then apply our approach to a large, clinically-derived dataset of Gag p17 and p24 sequences from a multicenter cohort of 1144 HIV-infected individuals from British Columbia, Canada (predominantly HIV-1 clade B and Durban, South Africa (predominantly HIV-1 clade C. The resulting phylogenetic dependency network is dense, containing 149 associations between HLA alleles and HIV codons and 1386 associations among HIV codons. These associations include the complete reconstruction of several recently defined escape and compensatory mutation pathways and agree with emerging data on patterns of epitope targeting. The phylogenetic dependency network adds to the growing body of literature suggesting that sites of escape, order of escape, and compensatory mutations are largely consistent even across different clades, although we also identify several differences between clades. As recent case studies have demonstrated, understanding both the complexity and the consistency of

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

    Science.gov (United States)

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

    2009-04-21

    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. 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. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease

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

    Directory of Open Access Journals (Sweden)

    Mixon Mark

    2009-04-01

    Full Text Available Abstract 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

  20. Early immune adaptation in HIV-1 revealed by population-level approaches.

    Science.gov (United States)

    Martin, Eric; Carlson, Jonathan M; Le, Anh Q; Chopera, Denis R; McGovern, Rachel; Rahman, Manal A; Ng, Carmond; Jessen, Heiko; Kelleher, Anthony D; Markowitz, Martin; Allen, Todd M; Milloy, M-J; Carrington, Mary; Wainberg, Mark A; Brumme, Zabrina L

    2014-08-29

    The reproducible nature of HIV-1 escape from HLA-restricted CD8+ T-cell responses allows the identification of HLA-associated viral polymorphisms "at the population level" - that is, via analysis of cross-sectional, linked HLA/HIV-1 genotypes by statistical association. However, elucidating their timing of selection traditionally requires detailed longitudinal studies, which are challenging to undertake on a large scale. We investigate whether the extent and relative timecourse of immune-driven HIV adaptation can be inferred via comparative cross-sectional analysis of independent early and chronic infection cohorts. Similarly-powered datasets of linked HLA/HIV-1 genotypes from individuals with early (median  200/dataset), HLA class I and HIV-1 Gag/Pol/Nef diversity, were established. These datasets were first used to define a list of 162 known HLA-associated polymorphisms detectable at the population level in cohorts of the present size and host/viral genetic composition. Of these 162 known HLA-associated polymorphisms, 15% (occurring at 14 Gag, Pol and Nef codons) were already detectable via statistical association in the early infection dataset at p ≤ 0.01 (q adaptations at Gag codons 397, 401 and 403). Escape prevalence in early infection correlated strongly with first-year escape rates (Pearson's R = 0.68, p = 0.0001), supporting cross-sectional parameters as reliable indicators of longitudinally-derived measures. Comparative analysis of early and chronic datasets revealed that, on average, the prevalence of HLA-associated polymorphisms more than doubles between these two infection stages in persons harboring the relevant HLA (p adaptation (via rapid escape and/or frequent polymorphism transmission) as a correlate of progression. Cross-sectional host/viral genotype datasets represent an underutilized resource to identify reproducible early pathways of HIV-1 adaptation and identify correlates of protective immunity.

  1. A new battery capacity indicator for nickel-metal hydride battery powered electric vehicles using adaptive neuro-fuzzy inference system

    CERN Document Server

    Chau, K T; Chan, C C; Shen, W X

    2003-01-01

    This paper describes a new approach to estimate accurately the battery residual capacity (BRC) of the nickel-metal hydride (Ni-MH) battery for modern electric vehicles (EVs). The key to this approach is to model the Ni-MH battery in EVs by using the adaptive neuro-fuzzy inference system (ANFIS) with newly defined inputs and output. The inputs are the temperature and the discharged capacity distribution describing the discharge current profile, while the output is the state of available capacity (SOAC) representing the BRC. The estimated SOAC from ANFIS model and the measured SOAC from experiments are compared, and the results confirm that the proposed approach can provide an accurate estimation of the SOAC under variable discharge currents.

  2. A codon-optimized bacterial antibiotic gene used as selection marker for stable nuclear transformation in the marine red alga Pyropia yezoensis.

    Science.gov (United States)

    Uji, Toshiki; Hirata, Ryo; Fukuda, Satoru; Mizuta, Hiroyuki; Saga, Naotsune

    2014-06-01

    Marine macroalgae play an important role in marine coastal ecosystems and are widely used as sea vegetation foodstuffs and for industrial purposes. Therefore, there have been increased demands for useful species and varieties of these macroalgae. However, genetic transformation in macroalgae has not yet been established. We have developed a dominant selection marker for stable nuclear transformation in the red macroalga Pyropia yezoensis. We engineered the coding region of the aminoglycoside phosphotransferase gene aph7″ from Streptomyces hygroscopicus to adapt codon usage of the nuclear genes of P. yezoensis. We designated this codon-optimized aph7″ gene as PyAph7. After bombarding P. yezoensis cells with plasmids containing PyAph7 under the control of their endogenous promoter, 1.9 thalli (or individuals) of hygromycin-resistant strains were isolated from a 10-mm square piece of the bombarded thallus. These transformants were stably maintained throughout the asexual life cycle. Stable expression of PyAph7was verified using Southern blot analysis and genomic PCR and RT-PCR analyses. PyAph7 proved to be a new versatile tool for stable nuclear transformation in P. yezoensis.

  3. Abortive translation caused by peptidyl-tRNA drop-off at NGG codons in the early coding region of mRNA

    DEFF Research Database (Denmark)

    Gonzalez de Valdivia, Ernesto I; Isaksson, Leif A

    2005-01-01

    In Escherichia coli the codons CGG, AGG, UGG or GGG (NGG codons) but not GGN or GNG (where N is non-G) are associated with low expression of a reporter gene, if located at positions +2 to +5. Induction of a lacZ reporter gene with any one of the NGG codons at position +2 to +5 does not influence ...

  4. New insights into the codon usage patterns of the bactericidal/permeability-increasing (BPI) gene across nine species.

    Science.gov (United States)

    Qin, Wei-Yun; Gan, Li-Na; Xia, Ri-Wei; Sun, Shou-Yong; Zhu, Guo-Qiang; Wu, Sheng-Long; Bao, Wen-Bin

    2017-06-15

    Bactericidal/permeability-increasing (BPI) protein is a member of a new generation of proteins known as super-antibiotics that are implicated as endotoxin neutralising agents. Non-uniform usage of synonymous codons for a specific amino acid during translation of a protein is known as codon usage bias (CUB). Analysis of CUB and compositional dynamics of coding sequences could contribute to a better understanding of the molecular mechanism and the evolution of a particular gene. In this study, we performed CUB analysis of the complete coding sequences of the BPI gene from nine different species. The codon usage patterns of BPI across different species were found to be influenced by GC bias, particularly GC3s, with a moderate bias in the codon usage of BPI. We found significant similarities in the codon usage patterns in BPI gene among closely related species, such as Sus_scrofa and Bos_taurus. Moreover, we observed evolutionary conservation of the most over-represented codon CUG for the amino acid leucine in the BPI gene across all species. In conclusion, our analysis provides a novel insight into the codon usage patterns of BPI. This information facilitates an improved understanding of the structural, functional and evolutionary significance of BPI gene among species, and provides a theoretical reference for developing antiseptic drug proteins with high efficiency across species. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    David J Hauber

    Full Text Available 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.

  6. Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins

    Directory of Open Access Journals (Sweden)

    Metzger Kelsey J

    2010-05-01

    Full Text Available Abstract Background CC chemokine receptor proteins (CCR1 through CCR10 are seven-transmembrane G-protein coupled receptors whose signaling pathways are known for their important roles coordinating immune system responses through targeted trafficking of white blood cells. In addition, some of these receptors have been identified as fusion proteins for viral pathogens: for example, HIV-1 strains utilize CCR5, CCR2 and CCR3 proteins to obtain cellular entry in humans. The extracellular domains of these receptor proteins are involved in ligand-binding specificity as well as pathogen recognition interactions. In mammals, the majority of chemokine receptor genes are clustered together; in humans, seven of the ten genes are clustered in the 3p21-24 chromosome region. Gene conversion events, or exchange of DNA sequence between genes, have been reported in chemokine receptor paralogs in various mammalian lineages, especially between the cytogenetically closely located pairs CCR2/5 and CCR1/3. Datasets of mammalian orthologs for each gene were analyzed separately to minimize the potential confounding impact of analyzing highly similar sequences resulting from gene conversion events. Molecular evolution approaches and the software package Phylogenetic Analyses by Maximum Likelihood (PAML were utilized to investigate the signature of selection that has acted on the mammalian CC chemokine receptor (CCR gene family. The results of neutral vs. adaptive evolution (positive selection hypothesis testing using Site Models are reported. In general, positive selection is defined by a ratio of nonsynonymous/synonymous nucleotide changes (dN/dS, or ω >1. Results Of the ten mammalian CC motif chemokine receptor sequence datasets analyzed, only CCR2 and CCR3 contain amino acid codon sites that exhibit evidence of positive selection using site based hypothesis testing in PAML. Nineteen of the twenty codon sites putatively indentified as likely to be under positive

  7. Investigating Low Adaptive Behaviour and Presence of the Triad of Impairments Characteristic of Autistic Spectrum Disorder as Indicators of Risk for Challenging Behaviour among Adults with Intellectual Disabilities

    Science.gov (United States)

    Felce, D.; Kerr, M.

    2013-01-01

    Background: Identification of possible personal indicators of risk for challenging behaviour has generally been through association in cross-sectional prevalence studies, but few analyses have controlled for intercorrelation between potential risk factors. The aim was to investigate the extent to which gender, age, presence of the triad of…

  8. Adaptive fisheries management in Vietnam: The use of indicators and the introduction of a multi-disciplinary Marine Fisheries Specialist Team to support implementation

    DEFF Research Database (Denmark)

    Raakjaer, J.; Son, D.M.; Stæhr, Karl-Johan

    2007-01-01

    or used in Vietnam including the data-collection system. The Vietnamese approach is supported by an institutional structure consisting of a multi-disciplinary advisory system to facilitate the process of using indicators and to introduce knowledge-based management. The article concludes by identifying...

  9. Angelman syndrome due to a termination codon mutation of the UBE3A gene.

    Science.gov (United States)

    Al-Maawali, Almundher; Machado, Jerry; Fang, Ping; Dupuis, Lucie; Faghfoury, Hannaneh; Mendoza-Londono, Roberto

    2013-03-01

    Angelman syndrome is a neurodevelopmental disorder characterized by global developmental delay, mental retardation, seizures, microcephaly, and severe speech delay. It may be caused by deletion of chromosome region 15q11.2 of the maternally inherited chromosome, mutations in the UBE3A gene, uniparental disomy, or imprinting defects. Most patients with this diagnosis have a severe phenotype, and a few have a mild form of the disease. We report a patient with a novel mutation in the UBE3A gene that consists of a deletion of the termination codon (c.2556-*+6del GTAAAACAAA) and results in an elongated protein E3 ubiquitin-protein ligase. Our patient has a mild phenotype compared with other patients in general and specifically to patients with UBE3A mutations. He has mild developmental delay, moderate speech delay, and no seizures. Recognition of this genotype-phenotype correlation will allow better genetic counseling to other patients with similar stop codon mutations.

  10. East Greenland and Barents Sea polar bears (Ursus maritimus): adaptive variation between two populations using skull morphometrics as an indicator of environmental and genetic differences.

    Science.gov (United States)

    Pertoldi, Cino; Sonne, Christian; Wiig, Øystein; Baagøe, Hans J; Loeschcke, Volker; Bechshøft, Thea Østergaard

    2012-06-01

    A morphometric study was conducted on four skull traits of 37 male and 18 female adult East Greenland polar bears (Ursus maritimus) collected 1892-1968, and on 54 male and 44 female adult Barents Sea polar bears collected 1950-1969. The aim was to compare differences in size and shape of the bear skulls using a multivariate approach, characterizing the variation between the two populations using morphometric traits as an indicator of environmental and genetic differences. Mixture analysis testing for geographic differentiation within each population revealed three clusters for Barents Sea males and three clusters for Barents Sea females. East Greenland consisted of one female and one male cluster. A principal component analysis (PCA) conducted on the clusters defined by the mixture analysis, showed that East Greenland and Barents Sea polar bear populations overlapped to a large degree, especially with regards to females. Multivariate analyses of variance (MANOVA) showed no significant differences in morphometric means between the two populations, but differences were detected between clusters from each respective geographic locality. To estimate the importance of genetics and environment in the morphometric differences between the bears, a PCA was performed on the covariance matrix derived from the skull measurements. Skull trait size (PC1) explained approx. 80% of the morphometric variation, whereas shape (PC2) defined approx. 15%, indicating some genetic differentiation. Hence, both environmental and genetic factors seem to have contributed to the observed skull differences between the two populations. Overall, results indicate that many Barents Sea polar bears are morphometrically similar to the East Greenland ones, suggesting an exchange of individuals between the two populations. Furthermore, a subpopulation structure in the Barents Sea population was also indicated from the present analyses, which should be considered with regards to future management

  11. Genome-wide analysis of codon usage bias in Bovine Coronavirus

    OpenAIRE

    Castells, Mat?as; Victoria, Mat?as; Colina, Rodney; Musto, H?ctor; Cristina, Juan

    2017-01-01

    Background Bovine coronavirus (BCoV) belong to the genus Betacoronavirus of the family Coronaviridae. BCoV are widespread around the world and cause enteric or respiratory infections among cattle, leading to important economic losses to the beef and dairy industry worldwide. To study the relation of codon usage among viruses and their hosts is essential to understand host-pathogen interaction, evasion from host?s immune system and evolution. Methods We performed a comprehensive analysis of co...

  12. GUG is an efficient initiation codon to translate the human mitochondrial ATP6 gene

    Czech Academy of Sciences Publication Activity Database

    Dubot, A.; Godinot, C.; Dumur, V.; Sablonniere, B.; Stojkovic, T.; Cuisset, J. M.; Vojtíšková, Alena; Pecina, Petr; Ješina, Pavel; Houštěk, Josef

    2004-01-01

    Roč. 313, č. 3 (2004), s. 687-693 ISSN 0006-291X R&D Projects: GA MŠk LN00A079; GA MZd NE6533 Grant - others:Fondation Jerome LeJeune(XE) Grant project; GA-(FR) CNRS; GA-(FR) Rhone Alpes Region Institutional research plan: CEZ:AV0Z5011922 Keywords : GUG initiation codon * ATP6 gene * mitochondrial diseases Subject RIV: CE - Biochemistry Impact factor: 2.904, year: 2004

  13. Lie Superalgebras and the Multiplet Structure of the Genetic Code I: Codon Representations

    OpenAIRE

    Forger, F. M.; Sachse, R. S.

    1998-01-01

    It has been proposed that the degeneracy of the genetic code,i.e., the phenomenon that different codons (base triplets) of DNA are transcribed into the same amino acid, may be interpreted as the result of a symmetry breaking process. In the initial work of Hornos & Hornos this picture was developed in the framework of simple Lie algebras. Here, we explore the possibility of explaining the degeneracy of the genetic code using basic classical Lie superalgebras, whose representation theory is su...

  14. Prevalence of codon 72 P53 polymorphism in Brazilian women with cervix cancer

    Directory of Open Access Journals (Sweden)

    Sylvia Michelina Fernandes Brenna

    2004-01-01

    Full Text Available The p53 codon 72 polymorphism seems to be associated with HPV-carcinogenesis, although controversial data have been reported. A series of Brazilian women with cervix carcinomas were analyzed. Ninety-nine (67% of 148 women were found to be homozygous (arg/arg for the arginine polymorphism, and 49 (33% were heterozygous (arg/pro. This polymorphism may be an important determinant of the risk for cervix cancer, but does not seem to be sufficient for carcinogenesis.

  15. Accessibility of the Shine-Dalgarno sequence dictates N-terminal codon bias in E. coli

    OpenAIRE

    Shakhnovich, Eugene; Zhang, Wenli; Yan, Jin; Adkar, Bharat; Jacobs, William; Bhattacharyya, Sanchari; Adkar, Bharat

    2018-01-01

    Despite considerable efforts, no physical mechanism has been shown to explain N-terminal codon bias in prokaryotic genomes. Using a systematic study of synonymous substitutions in two endogenous E. coli genes, we show that interactions between the coding region and the upstream Shine-Dalgarno (SD) sequence modulate the efficiency of translation initiation, affecting both intracellular mRNA and protein levels due to the inherent coupling of transcription and translation in E. coli. We further ...

  16. Mismatch repair at stop codons is directed independent of GATC methylation on the Escherichia coli chromosome

    Science.gov (United States)

    Sneppen, Kim; Semsey, Szabolcs

    2014-12-01

    The mismatch repair system (MMR) corrects replication errors that escape proofreading. Previous studies on extrachromosomal DNA in Escherichia coli suggested that MMR uses hemimethylated GATC sites to identify the newly synthesized strand. In this work we asked how the distance of GATC sites and their methylation status affect the occurrence of single base substitutions on the E. coli chromosome. As a reporter system we used a lacZ gene containing an early TAA stop codon. We found that occurrence of point mutations at this stop codon is unaffected by GATC sites located more than 115 base pairs away. However, a GATC site located about 50 base pairs away resulted in a decreased mutation rate. This effect was independent of Dam methylation. The reversion rate of the stop codon increased only slightly in dam mutants compared to mutL and mutS mutants. We suggest that unlike on extrachromosomal DNA, GATC methylation is not the only strand discrimination signal for MMR on the E. coli chromosome.

  17. Effect of correlated tRNA abundances on translation errors and evolution of codon usage bias.

    Directory of Open Access Journals (Sweden)

    Premal Shah

    2010-09-01

    Full Text Available Despite the fact that tRNA abundances are thought to play a major role in determining translation error rates, their distribution across the genetic code and the resulting implications have received little attention. In general, studies of codon usage bias (CUB assume that codons with higher tRNA abundance have lower missense error rates. Using a model of protein translation based on tRNA competition and intra-ribosomal kinetics, we show that this assumption can be violated when tRNA abundances are positively correlated across the genetic code. Examining the distribution of tRNA abundances across 73 bacterial genomes from 20 different genera, we find a consistent positive correlation between tRNA abundances across the genetic code. This work challenges one of the fundamental assumptions made in over 30 years of research on CUB that codons with higher tRNA abundances have lower missense error rates and that missense errors are the primary selective force responsible for CUB.

  18. Codon optimization significantly improves the expression level of a keratinase gene in Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Hong Hu

    Full Text Available The main keratinase (kerA gene from the Bacillus licheniformis S90 was optimized by two codon optimization strategies and expressed in Pichia pastoris in order to improve the enzyme production compared to the preparations with the native kerA gene. The results showed that the corresponding mutations (synonymous codons according to the codon bias in Pichia pastoris were successfully introduced into keratinase gene. The highest keratinase activity produced by P. pastoris pPICZαA-kerAwt, pPICZαA-kerAopti1 and pPICZαA-kerAopti2 was 195 U/ml, 324 U/ml and 293 U/ml respectively. In addition, there was no significant difference in biomass concentration, target gene copy numbers and relative mRNA expression levels of every positive strain. The molecular weight of keratinase secreted by recombinant P. pastori was approx. 39 kDa. It was optimally active at pH 7.5 and 50°C. The recombinant keratinase could efficiently degrade both α-keratin (keratin azure and β-keratin (chicken feather meal. These properties make the P. pastoris pPICZαA-kerAopti1 a suitable candidate for industrial production of keratinases.

  19. A novel framework for evaluating the performance of codon usage bias metrics.

    Science.gov (United States)

    Liu, Sophia S; Hockenberry, Adam J; Jewett, Michael C; Amaral, Luís A N

    2018-01-01

    The unequal utilization of synonymous codons affects numerous cellular processes including translation rates, protein folding and mRNA degradation. In order to understand the biological impact of variable codon usage bias (CUB) between genes and genomes, it is crucial to be able to accurately measure CUB for a given sequence. A large number of metrics have been developed for this purpose, but there is currently no way of systematically testing the accuracy of individual metrics or knowing whether metrics provide consistent results. This lack of standardization can result in false-positive and false-negative findings if underpowered or inaccurate metrics are applied as tools for discovery. Here, we show that the choice of CUB metric impacts both the significance and measured effect sizes in numerous empirical datasets, raising questions about the generality of findings in published research. To bring about standardization, we developed a novel method to create synthetic protein-coding DNA sequences according to different models of codon usage. We use these benchmark sequences to identify the most accurate and robust metrics with regard to sequence length, GC content and amino acid heterogeneity. Finally, we show how our benchmark can aid the development of new metrics by providing feedback on its performance compared to the state of the art. © 2018 The Author(s).

  20. C.U.R.R.F. (Codon Usage regarding Restriction Finder): a free Java(®)-based tool to detect potential restriction sites in both coding and non-coding DNA sequences.

    Science.gov (United States)

    Gatter, Michael; Gatter, Thomas; Matthäus, Falk

    2012-10-01

    The synthesis of complete genes is becoming a more and more popular approach in heterologous gene expression. Reasons for this are the decreasing prices and the numerous advantages in comparison to classic molecular cloning methods. Two of these advantages are the possibility to adapt the codon usage to the host organism and the option to introduce restriction enzyme target sites of choice. C.U.R.R.F. (Codon Usage regarding Restriction Finder) is a free Java(®)-based software program which is able to detect possible restriction sites in both coding and non-coding DNA sequences by introducing multiple silent or non-silent mutations, respectively. The deviation of an alternative sequence containing a desired restriction motive from the sequence with the optimal codon usage is considered during the search of potential restriction sites in coding DNA and mRNA sequences as well as protein sequences. C.U.R.R.F is available at http://www.zvm.tu-dresden.de/die_tu_dresden/fakultaeten/fakultaet_mathematik_und_naturwissenschaften/fachrichtung_biologie/mikrobiologie/allgemeine_mikrobiologie/currf.

  1. Analysis of four families with the Stickler syndrome by linkage studies. Identification of a new premature stop codon in the COL2A1 gene in a family

    Energy Technology Data Exchange (ETDEWEB)

    Bonaventure, J.; Lasselin, C. [Hopital Necker, Paris (France); Toutain, A. [CHU Bretonneau, Tours (France)] [and others

    1994-09-01

    The Stickler syndrome is an arthro-ophthalmopathy which associates progressive myopia with vitreal degeneration and retinal detachment. Cleft palate, cranio-facial abnormalities, deafness and osteoarthritis are often associated symptoms. Genetic heterogeneity of this autosomal dominant disease was consistent with its large clinical variability. Linkage studies have provided evidence for cosegregation of the disease with COL2A1, the gene coding for type II collagen, in about 50% of the families. Four additional families are reported here. Linkage analyses by using a VNTR located in the 3{prime} region of the gene were achieved. In three families, positive lod scores were obtained with a cumulative maximal value of 3.5 at a recombination fraction of 0. In one of these families, single strand conformation analysis of 25 exons disclosed a new mutation in exon 42. Codon for glutamic acid at position a1-803 was converted into a stop codon. The mutation was detected in DNA samples from all the affected members of the family but not in the unaffected. This result confirms that most of the Stickler syndromes linked to COL2A1 are due to premature stop codons. In a second family, an abnormal SSCP pattern of exon 34 was detected in all the affected individuals. The mutation is likely to correspond to a splicing defect in the acceptor site of intron 33. In one family the disease did not segregate with the COL2A1 locus. Further linkage studies with intragenic dimorphic sites in the COL10A1 gene and highly polymorphic markers close to the COL9A1 locus indicated that this disorder did not result from defects in these two genes.

  2. Assays to detect beta-tubulin codon 200 polymorphism in Trichuris trichiura and Ascaris lumbricoides.

    Science.gov (United States)

    Diawara, Aissatou; Drake, Lesley J; Suswillo, Richard R; Kihara, Jimmy; Bundy, Donald A P; Scott, Marilyn E; Halpenny, Carli; Stothard, J Russell; Prichard, Roger K

    2009-01-01

    The soil-transmitted helminths (STH) Ascaris lumbricoides and Trichuris trichiura are gastrointestinal parasites causing many disabilities to humans, particularly children. The benzimidazole (BZ) drugs, albendazole (ALB) and mebendazole (MBZ), are commonly used for mass treatment for STH. Unfortunately, there is concern that increased use of anthelmintics could select for resistant populations of these human parasites. In veterinary parasites, and lately in filarial nematodes, a single amino acid substitution from phenylalanine to tyrosine, known to be associated with benzimidazole resistance, has been found in parasite beta-tubulin at position 200. We have developed pyrosequencer assays for codon 200 (TTC or TAC) in A. lumbricoides and T. trichiura to screen for this single nucleotide polymorphism (SNP). Pyrosequencing assays were developed and evaluated for detecting the TTC or TAC SNP at codon 200 in beta-tubulin in A. lumbricoides and T. trichiura. Genomic DNA from individual worms, eggs isolated from individual adult worms or from fecal samples with known treatment history and origin, were sequenced at beta-tubulin by pyrosequencing, and genotypes were confirmed by conventional sequencing. The assays were applied to adult worms from a benzimidazole-naïve population in Kenya. Following this, these assays were applied to individual worms and pooled eggs from people in East Africa (Uganda and Zanzibar) and Central America (Panama) where mass anthelmintic drug programs had been implemented. All A. lumbricoides samples were TTC. However, we found 0.4% homozygous TAC/TAC in T. trichiura worms from non-treated people in Kenya, and 63% of T. trichiura egg pools from treated people in Panama contained only TAC. Although the codon 200 TAC SNP was not found in any of the A. lumbricoides samples analyzed, a rapid genotyping assay has been developed that can be used to examine larger populations of this parasite and to monitor for possible benzimidazole resistance

  3. Differentiating between near- and non-cognate codons in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Ewan P Plant

    2007-06-01

    Full Text Available Decoding of mRNAs is performed by aminoacyl tRNAs (aa-tRNAs. This process is highly accurate, however, at low frequencies (10(-3 - 10(-4 the wrong aa-tRNA can be selected, leading to incorporation of aberrant amino acids. Although our understanding of what constitutes the correct or cognate aa-tRNA:mRNA interaction is well defined, a functional distinction between near-cognate or single mismatched, and unpaired or non-cognate interactions is lacking.Misreading of several synonymous codon substitutions at the catalytic site of firefly luciferase was assayed in Saccharomyces cerevisiae. Analysis of the results in the context of current kinetic and biophysical models of aa-tRNA selection suggests that the defining feature of near-cognate aa-tRNAs is their potential to form mini-helical structures with A-site codons, enabling stimulation of GTPase activity of eukaryotic Elongation Factor 1A (eEF1A. Paromomycin specifically stimulated misreading of near-cognate but not of non-cognate aa-tRNAs, providing a functional probe to distinguish between these two classes. Deletion of the accessory elongation factor eEF1Bgamma promoted increased misreading of near-cognate, but hyperaccurate reading of non-cognate codons, suggesting that this factor also has a role in tRNA discrimination. A mutant of eEF1Balpha, the nucleotide exchange factor for eEF1A, promoted a general increase in fidelity, suggesting that the decreased rates of elongation may provide more time for discrimination between aa-tRNAs. A mutant form of ribosomal protein L5 promoted hyperaccurate decoding of both types of codons, even though it is topologically distant from the decoding center.It is important to distinguish between near-cognate and non-cognate mRNA:tRNA interactions, because such a definition may be important for informing therapeutic strategies for suppressing these two different categories of mutations underlying many human diseases. This study suggests that the defining feature

  4. TP53 Codon 72 Polymorphism and P53 Protein Expression in Colorectal Cancer Specimens in Isfahan

    Directory of Open Access Journals (Sweden)

    Mehdi Nikbahkt Dastjerdi

    2011-02-01

    Full Text Available The TP53 tumor suppressor gene plays important roles in genomic stability. A common polymorphism at codon 72 of TP53 gene has been associated with increased risk for many human cancers. The p53 protein is expressed in colorectal cancer, but the reported prevalence of its expression varies widely. In the present study, the p53 protein expression in different genotypes of its codon 72 , was investigated. We undertook a case-control study on 250 controls and 250 paraffin block specimens of sporadic colorectal adenocarcinomas from the city of Isfahan. PCR amplification of TP53 codon 72 polymorphism: TP53 codon 72 genotypes were detected by PCR using specific primer pairs for amplifying the proline or the arginine Alleles. The PCR reaction was done separately for each of the two polymorphic variants. The amplified products were subjected to electrophoresis on 1% agarose gel in 1× TBE buffer and visualized on a transilluminator using ethidium bromide. Immunohistochemical Staining: We evaluated the expression patterns of p53 protein, as potential prognostic marker in colorectal cancer specimens by immunohistochemical staining. Statistical analyses: The χ2-test was used to assess the significance of any difference in the prevalence of TP53 codon 72 polymorphism between colorectal cancer patients and controls. The odds ratio and 95% CI (confidence intervals was used as a measure of the strength of the association. Statistical significance level was set to P≤0.05. In control samples, the genotype distribution for TP53 polymorphism showed 30.4%, 45.2% and 24.4% for the arginine/arginine, arginine/proline and proline/proline genotypes, respectively. Allelic frequencies corresponded to 0.663 for the arginine allele and 0.338 for the proline allele. In the cancer group 38.8% of the cases were arginine/arginine, 40.4% were arginine/proline and 20.8% were proline/proline. The corresponding frequencies were 0.590 for the arginine allele and 0.410 for the

  5. In vitro cellular adaptations of indicators of longevity in response to treatment with serum collected from humans on calorie restricted diets.

    Directory of Open Access Journals (Sweden)

    Joanne S Allard

    2008-09-01

    Full Text Available Calorie restriction (CR produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period. Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1alpha mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans.

  6. Adaption of cardio-respiratory balance during day-rest compared to deep sleep--an indicator for quality of life?

    Science.gov (United States)

    von Bonin, Dietrich; Grote, Vincent; Buri, Caroline; Cysarz, Dirk; Heusser, Peter; Moser, Max; Wolf, Ursula; Laederach, Kurt

    2014-11-30

    Heart rate and breathing rate fluctuations represent interacting physiological oscillations. These interactions are commonly studied using respiratory sinus arrhythmia (RSA) of heart rate variability (HRV) or analyzing cardiorespiratory synchronization. Earlier work has focused on a third type of relationship, the temporal ratio of respiration rate and heart rate (HRR). Each method seems to reveal a specific aspect of cardiorespiratory interaction and may be suitable for assessing states of arousal and relaxation of the organism. We used HRR in a study with 87 healthy subjects to determine the ability to relax during 5 day-resting periods in comparison to deep sleep relaxation. The degree to which a person during waking state could relax was compared to somatic complaints, health-related quality of life, anxiety and depression. Our results show, that HRR is barely connected to balance (LF/HF) in HRV, but significantly correlates to the perception of general health and mental well-being as well as to depression. If relaxation, as expressed in HRR, during day-resting is near to deep sleep relaxation, the subjects felt healthier, indicated better mental well-being and less depressive moods. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. The Genome Sequence of the psychrophilic archaeon, Methanococcoides burtonii: the Role of Genome Evolution in Cold-adaptation

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Michelle A.; Lauro, Federico M.; Williams, Timothy J.; Burg, Dominic; Siddiqui, Khawar S.; De Francisci, David; Chong, Kevin W.Y.; Pilak, Oliver; Chew, Hwee H.; De Maere, Matthew Z.; Ting, Lily; Katrib, Marilyn; Ng, Charmaine; Sowers, Kevin R.; Galperin, Michael Y.; Anderson, Iain J.; Ivanova, Natalia; Dalin, Eileen; Martinez, Michelle; Lapidus, Alla; Hauser, Loren; Land, Miriam; Thomas, Torsten; Cavicchioli, Ricardo

    2009-04-01

    Psychrophilic archaea are abundant and perform critical roles throughout the Earth's expansive cold biosphere. Here we report the first complete genome sequence for a psychrophilic methanogenic archaeon, Methanococcoides burtonii. The genome sequence was manually annotated including the use of a five tiered Evidence Rating system that ranked annotations from Evidence Rating (ER) 1 (gene product experimentally characterized from the parent organism) to ER5 (hypothetical gene product) to provide a rapid means of assessing the certainty of gene function predictions. The genome is characterized by a higher level of aberrant sequence composition (51%) than any other archaeon. In comparison to hyper/thermophilic archaea which are subject to selection of synonymous codon usage, M. burtonii has evolved cold adaptation through a genomic capacity to accommodate highly skewed amino acid content, while retaining codon usage in common with its mesophilic Methanosarcina cousins. Polysaccharide biosynthesis genes comprise at least 3.3% of protein coding genes in the genome, and Cell wall/membrane/envelope biogenesis COG genes are over-represented. Likewise, signal transduction (COG category T) genes are over-represented and M. burtonii has a high 'IQ' (a measure of adaptive potential) compared to many methanogens. Numerous genes in these two over-represented COG categories appear to have been acquired from {var_epsilon}- and {delta}-proteobacteria, as do specific genes involved in central metabolism such as a novel B form of aconitase. Transposases also distinguish M. burtonii from other archaea, and their genomic characteristics indicate they play an important role in evolving the M. burtonii genome. Our study reveals a capacity for this model psychrophile to evolve through genome plasticity (including nucleotide skew, horizontal gene transfer and transposase activity) that enables adaptation to the cold, and to the biological and physical changes that have

  8. WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with Tumor Radioresistence: An Indication for Individualized Breast Cancer Therapy Adapted to Cancer Stem Cell Fractions

    Energy Technology Data Exchange (ETDEWEB)

    Qi, S; Pajonk, F; McCloskey, S; Low, D; Kupelian, P; Steinberg, M; Sheng, K [UCLA, Los Angeles, CA (United States)

    2014-06-15

    Purposes: The presence of cancer stem cells (CSCs) in a solid tumor could result in poor tumor control probability. The purposes are to study CSC radiosensitivity parameters α and β and their correlation to CSC levels to understand the underlying radioresistance mechanisms and enable individualized treatment design. Methods: Four established breast cancer cell lines (MCF-7, T47D, MDA-MB-231, and SUM159PT) were irradiated in vitro using single radiation doses of 0, 2, 4, 6, 8 or 10 Gy. The fractions of CSCs in each cell lines were determined using cancer stem cell markers. Mammosphere assays were also performed to better estimate the number of CSCs and represent the CSC repopulation in a human solid tumor. The measured cell surviving fractions were fitted using the Linear-quadratic (LQ) model with independent fitting parameters: α-TC, β-TC (TCs), α-CSC, β-CSC (CSCs), and fs (the percentage of CSCs in each sample). Results: The measured fs increased following the irradiation by MCF-7 (0.1%), T47D (0.9%), MDA-MB-231 (1.18%) and SUM159T (2.46%), while decreasing surviving curve slopes were observed, indicating greater radioresistance, in the opposite order. The fitting yielded the radiosensitive parameters for the MCF-7: α-TC=0.1±0.2Gy{sup −1}, β-TC= 0.08 ±0.14Gy{sup −2}, α-CSC=0.04±0.07Gy{sup −1}, β-CSC =0.02±0.3Gy{sup −2}; for the SUM159PT, α-TC=0.08±0.25 Gy{sup −1}, β-TC=0.02±0.02Gy{sup −2}, α-CSC=0.04±0.18Gy{sup −1}, β-CSC =0.004±0.24Gy{sup −2}. In the mammosphere assay, where fs were higher than the corresponding cell line assays, there was almost no shoulder found in the surviving curves (more radioresistant in mammosphere assays) yielding β-CSC of approximately 0. Conclusion: Breast cancer stem cells were more radioresistant characterized by smaller α and β values compared to differentiated breast cancer cells. Percentage of breast cancer stem cells strongly correlated to overall tumor radioresistance. This observation

  9. BRAF V600E mutation and KRAS codon 13 mutations predict poor survival in Chinese colorectal cancer patients.

    Science.gov (United States)

    Chen, Jing; Guo, Fang; Shi, Xin; Zhang, Lihua; Zhang, Aifeng; Jin, Hui; He, Youji

    2014-11-03

    Mutations in KRAS, BRAF and PIK3CA are the most common somatic alterations found in the colorectal cancer (CRC) patients from Western countries; but their prevalence and prognostic value have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of these genes in Chinese CRC patients and to investigate their impact on prognosis. The sequences of exon 2 of KRAS, exon 15 of BRAF and exons 9 and 20 of PIK3CA were evaluated by PCR and direct sequencing using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues from primary CRC tumors of 214 patients (colon/rectum: 126/88). KRAS, BRAF and PIK3CA mutations were identified in 44.9% (96/214), 4.2% (9/214) and 12.3% (26/212) CRCs, respectively. The most frequent mutations in KRAS, BRAF and PIK3CA were G12D, V600E and H1047R, respectively. All BRAF and 80.8% PIK3CA mutations were from colon cancer patients. BRAF V600E was associated with advanced TNM (P mutations (N = 25) had significantly worse OS (P = 0.016; multivariate HR = 2.7, P = 0.011), whereas KRAS codon 12-mutated cases were not significantly associated with survival. Among the three most common KRAS mutations, G13D (N = 23) showed significant association with poor OS (P = 0.024; multivariate HR = 2.6, P = 0.016) compared with KRAS wt/BRAF wt patients. Our findings indicate that PI3K/RAS-RAF signaling pathway genes are frequently mutated in Chinese CRC patients, but have different characteristics than found in Western patients. BRAF V600E is an independent prognostic factor for Chinese patients. Our finding that KRAS codon 13 mutations (in particular G13D) are associated with inferior survival in BRAF wild-type CRCs in Chinese patients was not reported thus far. Our data emphasizes the importance of prospective evaluation of molecular features in CRC patients, because a single mutation type may represent a distinct biologic effect and clinical implication.

  10. Computer-aided codon-pairs deoptimization of the major envelope GP5 gene attenuates porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Ni, Yan-Yan; Zhao, Zhao; Opriessnig, Tanja; Subramaniam, Sakthivel; Zhou, Lei; Cao, Dianjun; Cao, Qian; Yang, Hanchun; Meng, Xiang-Jin

    2014-02-01

    Synthetic attenuated virus engineering (SAVE) is an emerging technology that enables rapid attenuation of viruses. In this study, by using SAVE we demonstrated rapid attenuation of an arterivirus, porcine reproductive and respiratory syndrome virus (PRRSV). The major envelope GP5 gene of PRRSV was codon-pair deoptimized aided by a computer algorithm. The codon-pair deoptimized virus, designated as SAVE5 with a deoptimized GP5 gene, was successfully rescued in vitro. The SAVE5 virus replicated at a lower level in vitro with a significant decrease of GP5 protein expression compared to the wild-type PRRSV VR2385 virus. Pigs experimentally infected with the SAVE5 virus had significantly lower viremia level up to 14 days post-infection as well as significantly reduced gross and histological lung lesions when compared to wild-type PRRSV VR2385 virus-infected pigs, indicating the attenuation of the SAVE5 virus. This study proved the feasibility of rapidly attenuating PRRSV by SAVE. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Prevalence and distribution of Listeria monocytogenes inlA alleles prone to phase variation and inlA alleles with premature stop codon mutations among human, food, animal, and environmental isolates.

    Science.gov (United States)

    Manuel, Clyde S; Van Stelten, Anna; Wiedmann, Martin; Nightingale, Kendra K; Orsi, Renato H

    2015-12-01

    In Listeria monocytogenes, 18 mutations leading to premature stop codons (PMSCs) in the virulence gene inlA have been identified to date. While most of these mutations represent nucleotide substitutions, a frameshift deletion in a 5' seven-adenine homopolymeric tract (HT) in inlA has also been reported. This HT may play a role in phase variation and was first identified among L. monocytogenes lineage II ribotype DUP-1039C isolates. In order to better understand the distribution of different inlA mutations in this ribotype, a newly developed multiplex real-time PCR assay was used to screen 368 DUP-1039C isolates from human, animal, and food-associated sources for three known 5' inlA HT alleles: (i) wild-type (WT) (A7), (ii) frameshift (FS) (A6), and (iii) guanine interruption (A2GA4) alleles. Additionally, 228 DUP-1039C isolates were screened for all inlA PMSCs; data on the presence of all inlA PMSCs for the other 140 isolates were obtained from previous studies. The statistical analysis based on 191 epidemiologically unrelated strains showed that strains with inlA PMSC mutations (n = 41) were overrepresented among food-associated isolates, while strains encoding full-length InlA (n = 150) were overrepresented among isolates from farm animals and their environments. Furthermore, the A6 allele was overrepresented and the A7 allele was underrepresented among food isolates, while the A6 allele was underrepresented among farm and animal isolates. Our results indicate that genetic variation in inlA contributes to niche adaptation within the lineage II subtype DUP-1039C. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases.

    Science.gov (United States)

    Kandeel, Mahmoud; Altaher, Abdallah

    2017-07-01

    Middle East respiratory syndrome coronavirus (MERS CoV) is a recently evolved fatal respiratory disease that poses a concern for a global epidemic. MERS CoV encodes 2 proteases, 3C-like protease (3CLpro) and papain-like protease (PLpro). These proteases share in processing MERS CoV polyproteins at different sites to yield 16 nonstructural proteins. In this work, we provide evidence that MERS CoV 3CLpro and PLpro are subject to different genetic and evolutionary influences that shape the protein sequence, codon usage pattern, and codon usage bias. Compositional bias is present in both proteins due to a preference for AT nucleotides. Thymidine (T) was highly preferred at the third position of codons, preferred and overrepresented codons in PLpro, but was replaced by guanosine (G) in 3CLpro. Compositional constraints were important in PLpro but not in 3CLpro. Directed mutation pressure seems to have a strong influence on 3CLpro codon usage, which is more than 30-fold higher than that in PLpro. Translational selection was evident with PLpro but not with 3CLpro. Both proteins are less immunogenic by showing low CpG frequencies. Correspondence analysis reveals the presence of 3 genetic clusters based on codon usage in PLpro and 3CLpro. Every protein had one common cluster and 2 different clusters. As revealed by correspondence analysis, the number of influences on codon usage are restricted in MERS CoV 3CLpro. In contrast, PLpro is controlled by a broader range of compositional, mutational, and other influences. This may be due to the multifunctional protease, deubiquitination, and innate immunity suppressing profiles of PLpro.

  13. Thermostable proteins bioprocesses: The activity of restriction endonuclease-methyltransferase from Thermus thermophilus (RM.TthHB27I cloned in Escherichia coli is critically affected by the codon composition of the synthetic gene.

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    Daria Krefft

    Full Text Available Obtaining thermostable enzymes (thermozymes is an important aspect of biotechnology. As thermophiles have adapted their genomes to high temperatures, their cloned genes' expression in mesophiles is problematic. This is mainly due to their high GC content, which leads to the formation of unfavorable secondary mRNA structures and codon usage in Escherichia coli (E. coli. RM.TthHB27I is a member of a family of bifunctional thermozymes, containing a restriction endonuclease (REase and a methyltransferase (MTase in a single polypeptide. Thermus thermophilus HB27 (T. thermophilus produces low amounts of RM.TthHB27I with a unique DNA cleavage specificity. We have previously cloned the wild type (wt gene into E. coli, which increased the production of RM.TthHB27I over 100-fold. However, its enzymatic activities were extremely low for an ORF expressed under a T7 promoter. We have designed and cloned a fully synthetic tthHB27IRM gene, using a modified 'codon randomization' strategy. Codons with a high GC content and of low occurrence in E. coli were eliminated. We incorporated a stem-loop circuit, devised to negatively control the expression of this highly toxic gene by partially hiding the ribosome-binding site (RBS and START codon in mRNA secondary structures. Despite having optimized 59% of codons, the amount of produced RM.TthHB27I protein was similar for both recombinant tthHB27IRM gene variants. Moreover, the recombinant wt RM.TthHB27I is very unstable, while the RM.TthHB27I resulting from the expression of the synthetic gene exhibited enzymatic activities and stability equal to the native thermozyme isolated from T. thermophilus. Thus, we have developed an efficient purification protocol using the synthetic tthHB27IRM gene variant only. This suggests the effect of co-translational folding kinetics, possibly affected by the frequency of translational errors. The availability of active RM.TthHB27I is of practical importance in molecular biotechnology

  14. Thermostable proteins bioprocesses: The activity of restriction endonuclease-methyltransferase from Thermus thermophilus (RM.TthHB27I) cloned in Escherichia coli is critically affected by the codon composition of the synthetic gene.

    Science.gov (United States)

    Krefft, Daria; Papkov, Aliaksei; Zylicz-Stachula, Agnieszka; Skowron, Piotr M

    2017-01-01

    Obtaining thermostable enzymes (thermozymes) is an important aspect of biotechnology. As thermophiles have adapted their genomes to high temperatures, their cloned genes' expression in mesophiles is problematic. This is mainly due to their high GC content, which leads to the formation of unfavorable secondary mRNA structures and codon usage in Escherichia coli (E. coli). RM.TthHB27I is a member of a family of bifunctional thermozymes, containing a restriction endonuclease (REase) and a methyltransferase (MTase) in a single polypeptide. Thermus thermophilus HB27 (T. thermophilus) produces low amounts of RM.TthHB27I with a unique DNA cleavage specificity. We have previously cloned the wild type (wt) gene into E. coli, which increased the production of RM.TthHB27I over 100-fold. However, its enzymatic activities were extremely low for an ORF expressed under a T7 promoter. We have designed and cloned a fully synthetic tthHB27IRM gene, using a modified 'codon randomization' strategy. Codons with a high GC content and of low occurrence in E. coli were eliminated. We incorporated a stem-loop circuit, devised to negatively control the expression of this highly toxic gene by partially hiding the ribosome-binding site (RBS) and START codon in mRNA secondary structures. Despite having optimized 59% of codons, the amount of produced RM.TthHB27I protein was similar for both recombinant tthHB27IRM gene variants. Moreover, the recombinant wt RM.TthHB27I is very unstable, while the RM.TthHB27I resulting from the expression of the synthetic gene exhibited enzymatic activities and stability equal to the native thermozyme isolated from T. thermophilus. Thus, we have developed an efficient purification protocol using the synthetic tthHB27IRM gene variant only. This suggests the effect of co-translational folding kinetics, possibly affected by the frequency of translational errors. The availability of active RM.TthHB27I is of practical importance in molecular biotechnology, extending

  15. Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons.

    Science.gov (United States)

    Macvanin, Mirjana; Gonzalez de Valdivia, Ernesto I; Ardell, David H; Isaksson, Leif A

    2007-12-01

    Expression of minigenes encoding tetra- or pentapeptides MXLX or MXLXV (E peptides), where X is a nonpolar amino acid, renders cells erythromycin resistant whereas expression of minigenes encoding tripeptide MXL does not. By using a 3A' reporter gene system beginning with an E-peptide-encoding sequence, we asked whether the codons UGG and GGG, which are known to promote peptidyl-tRNA drop-off at early positions in mRNA, would result in a phenotype of erythromycin resistance if located after this sequence. We find that UGG or GGG, at either position +4 or +5, without a following stop codon, is associated with an erythromycin resistance phenotype upon gene induction. Our results suggest that, while a stop codon at +4 gives a tripeptide product (MIL) and erythromycin sensitivity, UGG or GGG codons at the same position give a tetrapeptide product (MILW or MILG) and phenotype of erythromycin resistance. Thus, the drop-off event on GGG or UGG codons occurs after incorporation of the corresponding amino acid into the growing peptide chain. Drop-off gives rise to a peptidyl-tRNA where the peptide moiety functionally mimics a minigene peptide product of the type previously associated with erythromycin resistance. Several genes in Escherichia coli fulfill the requirements of high mRNA expression and an E-peptide sequence followed by UGG or GGG at position +4 or +5 and should potentially be able to give an erythromycin resistance phenotype.

  16. Comprehensive analysis of the codon usage patterns in the envelope glycoprotein E2 gene of the classical swine fever virus.

    Directory of Open Access Journals (Sweden)

    Ye Chen

    Full Text Available The classical swine fever virus (CSFV, circulating worldwide, is a highly contagious virus. Since the emergence of CSFV, it has caused great economic loss in swine industry. The envelope glycoprotein E2 gene of the CSFV is an immunoprotective antigen that induces the immune system to produce neutralizing antibodies. Therefore, it is essential to study the codon usage of the E2 gene of the CSFV. In this study, 140 coding sequences of the E2 gene were analyzed. The value of effective number of codons (ENC showed low codon usage bias in the E2 gene. Our study showed that codon usage could be described mainly by mutation pressure ENC plot analysis combined with principal component analysis (PCA and translational selection-correlation analysis between the general average hydropathicity (Gravy and aromaticity (Aroma, and nucleotides at the third position of codons (A3s, T3s, G3s, C3s and GC3s. Furthermore, the neutrality analysis, which explained the relationship between GC12s and GC3s, revealed that natural selection had a key role compared with mutational bias during the evolution of the E2 gene. These results lay a foundation for further research on the molecular evolution of CSFV.

  17. Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses.

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    Angelo Pavesi

    Full Text Available 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.

  18. A codon-optimized green fluorescent protein for live cell imaging in Zymoseptoria tritici.

    Science.gov (United States)

    Kilaru, S; Schuster, M; Studholme, D; Soanes, D; Lin, C; Talbot, N J; Steinberg, G

    2015-06-01

    Fluorescent proteins (FPs) are powerful tools to investigate intracellular dynamics and protein localization. Cytoplasmic expression of FPs in fungal pathogens allows greater insight into invasion strategies and the host-pathogen interaction. Detection of their fluorescent signal depends on the right combination of microscopic setup and signal brightness. Slow rates of photo-bleaching are pivotal for in vivo observation of FPs over longer periods of time. Here, we test green-fluorescent proteins, including Aequorea coerulescens GFP (AcGFP), enhanced GFP (eGFP) from Aequorea victoria and a novel Zymoseptoria tritici codon-optimized eGFP (ZtGFP), for their usage in conventional and laser-enhanced epi-fluorescence, and confocal laser-scanning microscopy. We show that eGFP, expressed cytoplasmically in Z. tritici, is significantly brighter and more photo-stable than AcGFP. The codon-optimized ZtGFP performed even better than eGFP, showing significantly slower bleaching and a 20-30% further increase in signal intensity. Heterologous expression of all GFP variants did not affect pathogenicity of Z. tritici. Our data establish ZtGFP as the GFP of choice to investigate intracellular protein dynamics in Z. tritici, but also infection stages of this wheat pathogen inside host tissue. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Real-time tRNA transit on single translating ribosomes at codon resolution

    Science.gov (United States)

    Uemura, Sotaro; Aitken, Colin Echeverría; Korlach, Jonas; Flusberg, Benjamin A.; Turner, Stephen W.; Puglisi, Joseph D.

    2015-01-01

    Translation by the ribosome occurs by a complex mechanism involving the coordinated interaction of multiple nucleic acid and protein ligands. Here we have used zero-mode waveguides (ZMWs) and sophisticated detection instrumentation to allow real-time observation of translation at physiologically-relevant (μM) ligand concentrations. Translation at each codon is monitored by stable binding of tRNAs – labeled with distinct fluorophores – to translating ribosomes, allowing direct detection of the identity of tRNA molecules bound to the ribosome, and therefore, the underlying mRNA sequence. We observe the transit of tRNAs on single translating ribosomes and have determined the number of tRNA molecules simultaneously bound to the ribosome, at each codon of an mRNA. Our results show that ribosomes are only briefly occupied by two tRNAs and that release of deacylated tRNA from the E site is uncoupled from binding of A-site tRNA and occurs rapidly after translocation. The methods outlined here have broad application to the study of mRNA sequences, and the mechanism and regulation of translation. PMID:20393556

  20. Codon-Optimized Luciola Italica Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo

    Directory of Open Access Journals (Sweden)

    Casey A. Maguire

    2012-01-01

    Full Text Available Luciferases have proven to be useful tools in advancing our understanding of biologic processes. Having a multitude of bioluminescent reporters with different properties is highly desirable. We characterized codon-optimized thermostable green- and red-emitting luciferase variants from the Italian firefly Luciola italica for mammalian gene expression in culture and in vivo. Using lentivirus vectors to deliver and stably express these luciferases in mammalian cells, we showed that both variants displayed similar levels of activity and protein half-lives as well as similar light emission kinetics and higher stability compared to the North American firefly luciferase. Further, we characterized the red-shifted variant for in vivo bioluminescence imaging. Intramuscular injection of tumor cells stably expressing this variant into nude mice yielded a robust luciferase activity. Light emission peaked at 10 minutes post-D-luciferin injection and retained > 60% of signal at 1 hour. Similarly, luciferase activity from intracranially injected glioma cells expressing the red-shifted variant was readily detected and used as a marker to monitor tumor growth over time. Overall, our characterization of these codon-optimized luciferases lays the groundwork for their further use as bioluminescent reporters in mammalian cells.

  1. Assays to Detect β-Tubulin Codon 200 Polymorphism in Trichuris trichiura and Ascaris lumbricoides

    Science.gov (United States)

    Diawara, Aissatou; Drake, Lesley J.; Kihara, Jimmy; Bundy, Donald A. P.; Scott, Marilyn E.; Halpenny, Carli; Stothard, J. Russell; Prichard, Roger K.

    2009-01-01

    Background The soil-transmitted helminths (STH) Ascaris lumbricoides and Trichuris trichiura are gastrointestinal parasites causing many disabilities to humans, particularly children. The benzimidazole (BZ) drugs, albendazole (ALB) and mebendazole (MBZ), are commonly used for mass treatment for STH. Unfortunately, there is concern that increased use of anthelmintics could select for resistant populations of these human parasites. In veterinary parasites, and lately in filarial nematodes, a single amino acid substitution from phenylalanine to tyrosine, known to be associated with benzimidazole resistance, has been found in parasite β-tubulin at position 200. We have developed pyrosequencer assays for codon 200 (TTC or TAC) in A. lumbricoides and T. trichiura to screen for this single nucleotide polymorphism (SNP). Method and Findings Pyrosequencing assays were developed and evaluated for detecting the TTC or TAC SNP at codon 200 in β-tubulin in A. lumbricoides and T. trichiura. Genomic DNA from individual worms, eggs isolated from individual adult worms or from fecal samples with known treatment history and origin, were sequenced at β-tubulin by pyrosequencing, and genotypes were confirmed by conventional sequencing. The assays were applied to adult worms from a benzimidazole-naïve population in Kenya. Following this, these assays were applied to individual worms and pooled eggs from people in East Africa (Uganda and Zanzibar) and Central America (Panama) where mass anthelmintic drug programs had been implemented. All A. lumbricoides samples were TTC. However, we found 0.4% homozygous TAC/TAC in T. trichiura worms from non-treated people in Kenya, and 63% of T. trichiura egg pools from treated people in Panama contained only TAC. Conclusion Although the codon 200 TAC SNP was not found in any of the A. lumbricoides samples analyzed, a rapid genotyping assay has been developed that can be used to examine larger populations of this parasite and to monitor for

  2. Adaptive capability as indicated by behavioral and physiological responses, plasma HSP70 level, and PBMC HSP70 mRNA expression in Osmanabadi goats subjected to combined (heat and nutritional) stressors

    Science.gov (United States)

    Shilja, Shaji; Sejian, V.; Bagath, M.; Mech, A.; David, C. G.; Kurien, E. K.; Varma, Girish; Bhatta, Raghavendra

    2016-09-01

    A study was conducted to assess the impact of heat and nutritional stress simultaneously on the adaptive capability as indicated by behavioral and physiological responses, plasma heat shock protein 70 (HSP70) level, and peripheral blood mononuclear cells (PBMC) HSP70 gene expression in goats. Twenty-four adult Osmanabadi bucks (average body weight (BW) 16.0 kg) were used in the present study. The bucks were divided into four groups viz., C ( n = 6; control), HS ( n = 6; heat stress), NS ( n = 6; nutritional stress), and CS ( n = 6; combined stress). The study was conducted for a period of 45 days. C and HS bucks had ad libitum access to their feed while NS and CS bucks were under restricted feed (30 % intake of C bucks) to induce nutritional stress. The HS and CS bucks were exposed to solar radiation for 6 h a day between 10:00 a.m. and 4:00 p.m. to induce heat stress. The data was analyzed using repeated measures analysis of variance. The standing time differed significantly ( P Water intake recorded was significantly ( P < 0.01) higher in both the HS and CS groups. The highest respiration rate (RR), pulse rate (PR), and rectal temperature (RT) during the afternoon were also recorded in the CS group. Further, skin temperature of the head, flank, and scrotum during the afternoon was also higher ( P < 0.01) in the CS group. In addition, both plasma HSP70 concentration and PBMC HSP70 messenger RNA (mRNA) transcript expression were also significantly ( P < 0.01) higher in the CS group. It can be concluded from this study that when two stressors occur simultaneously, they may have severe impact on adaptive capabilities of Osmanabadi bucks as compared to that would occur individually. Further, the study indicated that lying time, drinking frequency, RR, RT, plasma HSP70, and PBMC HSP70 gene expression may act as ideal biological markers for assessing the impact of CS on adaptive capabilities in bucks.

  3. Three types of preS1 start codon deletion variants in the natural course of chronic hepatitis B infection.

    Science.gov (United States)

    Choe, Won Hyeok; Kim, Hong; Lee, So-Young; Choi, Yu-Min; Kwon, So Young; Moon, Hee Won; Hur, Mina; Kim, Bum-Joon

    2017-12-12

    Naturally occurring hepatitis B virus variants carrying a deletion in the preS1 start codon region may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The aim of this study was to determine the immune phase-specific prevalent patterns of preS1 start codon deletion variants and related factors during the natural course of CHB. A total of 399 CHB patients were enrolled. Genotypic analysis of three different preS1 start codon deletion variants (classified by deletion size: 15-base pair [bp], 18-bp, and 21-bp deletion variants) was performed. PreS1 start codon deletion variants were detected in 155 of 399 patients (38.8%). The predominant variant was a 15-bp deletion in the immune-tolerance phase (18/50, 36%) and an 18-bp deletion in the immune-clearance phase (69/183, 37.7%). A 21-bp deletion was the predominant variant in the low replicative phase (3/25, 12.0%) and reactivated hepatitis Be antigen (HBeAg)-negative phase (22/141, 15.6%). The 15-bp and 18-bp deletion variants were more frequently found in HBeAg-positive patients (P start codon deletion variants changes according to the immune phases of CHB infection, and each variant type is associated with different clinical parameters. PreS1 start codon deletion variants might interact with the host immune response differently according to their variant types. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  4. Contrasting Codon Usage Patterns and Purifying Selection at the Mating Locus in Putatively Asexual Alternaria Fungal Species

    Science.gov (United States)

    Stewart, Jane E.; Kawabe, Masato; Abdo, Zaid; Arie, Tsutomu; Peever, Tobin L.

    2011-01-01

    Sexual reproduction in heterothallic ascomycete fungi is controlled by a single mating-type locus called MAT1 with two alternate alleles or idiomorphs, MAT1-1 and MAT1-2. These alleles lack sequence similarity and encode different transcriptional regulators. A large number of phytopathogenic fungi including Alternaria spp. are considered asexual, yet still carry expressed MAT1 genes. The molecular evolution of Alternaria MAT1 was explored using nucleotide diversity, nonsynonymous vs. synonymous substitution (dn/ds) ratios and codon usage statistics. Likelihood ratio tests of site-branch models failed to detect positive selection on MAT1-1-1 or MAT1-2-1. Codon-site models demonstrated that both MAT1-1-1 and MAT1-2-1 are under purifying selection and significant differences in codon usage were observed between MAT1-1-1 and MAT1-2-1. Mean GC content at the third position (GC3) and effective codon usage (ENC) were significantly different between MAT1-1-1 and MAT1-2-1 with values of 0.57 and 48 for MAT1-1-1 and 0.62 and 46 for MAT1-2-1, respectively. In contrast, codon usage of Pleospora spp. (anamorph Stemphylium), a closely related Dothideomycete genus, was not significantly different between MAT1-1-1 and MAT1-2-1. The purifying selection and biased codon usage detected at the MAT1 locus in Alternaria spp. suggest a recent sexual past, cryptic sexual present and/or that MAT1 plays important cellular role(s) in addition to mating. PMID:21625561

  5. Elevation of the Yields of Very Long Chain Polyunsaturated Fatty Acids via Minimal Codon Optimization of Two Key Biosynthetic Enzymes.

    Directory of Open Access Journals (Sweden)

    Fei Xia

    Full Text Available Eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17 and Docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19 are nutritionally beneficial to human health. Transgenic production of EPA and DHA in oilseed crops by transferring genes originating from lower eukaryotes, such as microalgae and fungi, has been attempted in recent years. However, the low yield of EPA and DHA produced in these transgenic crops is a major hurdle for the commercialization of these transgenics. Many factors can negatively affect transgene expression, leading to a low level of converted fatty acid products. Among these the codon bias between the transgene donor and the host crop is one of the major contributing factors. Therefore, we carried out codon optimization of a fatty acid delta-6 desaturase gene PinD6 from the fungus Phytophthora infestans, and a delta-9 elongase gene, IgASE1 from the microalga Isochrysis galbana for expression in Saccharomyces cerevisiae and Arabidopsis respectively. These are the two key genes encoding enzymes for driving the first catalytic steps in the Δ6 desaturation/Δ6 elongation and the Δ9 elongation/Δ8 desaturation pathways for EPA/DHA biosynthesis. Hence expression levels of these two genes are important in determining the final yield of EPA/DHA. Via PCR-based mutagenesis we optimized the least preferred codons within the first 16 codons at their N-termini, as well as the most biased CGC codons (coding for arginine within the entire sequences of both genes. An expression study showed that transgenic Arabidopsis plants harbouring the codon-optimized IgASE1 contained 64% more elongated fatty acid products than plants expressing the native IgASE1 sequence, whilst Saccharomyces cerevisiae expressing the codon optimized PinD6 yielded 20 times more desaturated products than yeast expressing wild-type (WT PinD6. Thus the codon optimization strategy we developed here offers a simple, effective and low-cost alternative to whole gene synthesis for high

  6. Adaptive Modular Playware

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Þorsteinsson, Arnar Tumi

    2011-01-01

    In this paper, we describe the concept of adaptive modular playware, where the playware adapts to the interaction of the individual user. We hypothesize that there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user...... test set, the results are important as a proof of existence of differences and of the need for adaptation. The fact that there are individual differences makes the results significant for the development of games and interaction. It indicates that it is necessary to adapt the game and interaction......, if we desire to make the most appropriate game and interaction for the individual. Hence, we investigate adaptation as an important issue for playware. With simple playware games, we show that the adaptation will speed the game up and down to find the appropriate level that matches the reaction speed...

  7. Improved production of membrane proteins in Escherichia coli by selective codon substitutions

    DEFF Research Database (Denmark)

    Nørholm, Morten H.H.; Toddo, Stephen; Virkki, Minttu T.I.

    2013-01-01

    Membrane proteins are extremely challenging to produce in sufficient quantities for biochemical and structural analysis and there is a growing demand for solutions to this problem. In this study we attempted to improve expression of two difficult-to-express coding sequences (araH and narK) for me......Membrane proteins are extremely challenging to produce in sufficient quantities for biochemical and structural analysis and there is a growing demand for solutions to this problem. In this study we attempted to improve expression of two difficult-to-express coding sequences (araH and nar......-wired for high-level protein expression by selective engineering of the 5′ coding sequence with synonymous codons, thus circumventing the need to consider whole sequence optimization....

  8. A combination dimensionality reduction approach to codon position patterns of eubacteria based on their complete genomes.

    Science.gov (United States)

    Qi, Zhao-Hui; Wei, Ruo-Yan

    2011-03-07

    Graphical techniques have become powerful tools for the visualization and analysis of complicated biological systems. However, we cannot give such a graphical representation in a 2D/3D space when the dimensions of the represented data are more than three dimensions. The proposed method, a combination dimensionality reduction approach (CDR), consists of two parts: (i) principal component analysis (PCA) with a newly defined parameter ρ and (ii) locally linear embedding (LLE) with a proposed graphical selection for its optional parameter k. The CDR approach with ρ and k not only avoids loss of principal information, but also sufficiently well preserves the global high-dimensional structures in low-dimensional space such as 2D or 3D. The applications of the CDR on characteristic analysis at different codon positions in genome show that the method is a useful tool by which biologists could find useful biological knowledge. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Enhanced expression of lipase I from Galactomyces geotrichum by codon optimisation in Pichia pastoris.

    Science.gov (United States)

    Qiao, Hanzhen; Zhang, Wenfei; Guan, Wutai; Chen, Fang; Zhang, Shihai; Deng, Zixiao

    2017-10-01

    Relatively poor heterologous protein yields have limited the commerical applications of Galactomyces geotrichum lipase I (GGl I) efficacy trials. To address this, we have redesigned the GGl I gene to preferentially match codon frequencies of Pichia pastoris (P. pastoris) while retaining the same amino acid sequence. The wild type and codon optimised GGl I (GGl I-wt and GGl I-op) were synthesised and cloned into pPICZαA with an N-terminal 6 × His tag sequence and expressed in P. pastoris X 33. The hydrolytic activity of GGl I-op was 150 U/mL, whereas the activity of the GGl I-wt could not be detected. GGl I-op recombinant proteins were purified by Ni-affinity chromatography and then characterised. The identity and purity of GGl I were confirmed by SDS-PAGE, MALDI-TOF mass spectrometry and Western blot analysis. Enzymatic deglycosylation was used to show that the lipase is a glycosylated protein, containing ∼10% sugar. The molecular weight (MW) of the GGl I secreted by recombinant P. pastoris was approximated at 63 kDa. The optimum pH and temperature of the recombinant lipase were 8.0 and 35 °C, respectively. The enzyme was active over a broad pH range (7.0-9.0) and temperature range (20 °C-45 °C). The lipase showed high activity toward medium- and long-chain fatty acid methyl esters (C8-C16) and retained much of its activity in the presence of Tween-80 and Trition X-100. Lipase activity was stimulated by Mg 2+ , Ca 2+ , Mn 2+ and Cu 2+ and inhibited by Fe 2+ , Fe 3+ , Zn 2+ and Co 2+ . This lipase may prove useful to the detergent industry and in organic synthesis reactions. Copyright © 2017. Published by Elsevier Inc.

  10. The silent codon change I507-ATC→ATT contributes to the severity of the ΔF508 CFTR channel dysfunction

    Science.gov (United States)

    Lazrak, Ahmed; Fu, Lianwu; Bali, Vedrana; Bartoszewski, Rafal; Rab, Andras; Havasi, Viktoria; Keiles, Steve; Kappes, John; Kumar, Ranjit; Lefkowitz, Elliot; Sorscher, Eric J.; Matalon, Sadis; Collawn, James F.; Bebok, Zsuzsanna

    2013-01-01

    The most common disease-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is the out-of-frame deletion of 3 nucleotides (CTT). This mutation leads to the loss of phenylalanine-508 (ΔF508) and a silent codon change (SCC) for isoleucine-507 (I507-ATC→ATT). ΔF508 CFTR is misfolded and degraded by endoplasmic reticulum-associated degradation (ERAD). We have demonstrated that the I507-ATC→ATT SCC alters ΔF508 CFTR mRNA structure and translation dynamics. By comparing the biochemical and functional properties of the I507-ATT and I507-ATC ΔF508 CFTR, we establish that the I507-ATC→ATT SCC contributes to the cotranslational misfolding, ERAD, and to the functional defects associated with ΔF508 CFTR. We demonstrate that the I507-ATC ΔF508 CFTR is less susceptible to the ER quality-control machinery during translation than the I507-ATT, although 27°C correction is necessary for sufficient cell-surface expression. Whole-cell patch-clamp recordings indicate sustained, thermally stable cAMP-activated Cl− transport through I507-ATC and unstable function of the I507-ATT ΔF508 CFTR. Single-channel recordings reveal improved gating properties of the I507-ATC compared to I507-ATT ΔF508 CFTR (NPo=0.45±0.037 vs. NPo=0.09±0.002; P<0.001). Our results signify the role of the I507-ATC→ATT SCC in the ΔF508 CFTR defects and support the importance of synonymous codon choices in determining the function of gene products.—Lazrak, A., Fu, L., Bali, V., Bartoszewski, R., Rab, A., Havasi, V., Keiles, S., Kappes, J., Kumar, R., Lefkowitz, E., Sorscher, E. J., Matalon, S., Collawn, J. F., Bebok, Z. The silent codon change I507-ATC→ATT contributes to the severity of the ΔF508 CFTR. PMID:23907436

  11. Large scale comparative codon-pair context analysis unveils general rules that fine-tune evolution of mRNA primary structure.

    Directory of Open Access Journals (Sweden)

    Gabriela Moura

    Full Text Available BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage.

  12. Differential selective constraints shaping codon usage pattern of housekeeping and tissue-specific homologous genes of rice and arabidopsis.

    Science.gov (United States)

    Mukhopadhyay, Pamela; Basak, Surajit; Ghosh, Tapash Chandra

    2008-12-01

    Intra-genomic variation between housekeeping and tissue-specific genes has always been a study of interest in higher eukaryotes. To-date, however, no such investigation has been done in plants. Availability of whole genome expression data for both rice and Arabidopsis has made it possible to examine the evolutionary forces in shaping codon usage pattern in both housekeeping and tissue-specific genes in plants. In the present work, we have taken 4065 rice-Arabidopsis homologous gene pairs to study evolutionary forces responsible for codon usage divergence between housekeeping and tissue-specific genes. In both rice and Arabidopsis, it is mutational bias that regulates error minimization in highly expressed genes of both housekeeping and tissue-specific genes. Our results show that, in comparison to tissue-specific genes, housekeeping genes are under strong selective constraint in plants. However, in tissue-specific genes, lowly expressed genes are under stronger selective constraint compared with highly expressed genes. We demonstrated that constraint acting on mRNA secondary structure is responsible for modulating codon usage variations in rice tissue-specific genes. Thus, different evolutionary forces must underline the evolution of synonymous codon usage of highly expressed genes of housekeeping and tissue-specific genes in rice and Arabidopsis.

  13. The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

    DEFF Research Database (Denmark)

    Bentzen, J; Poulsen, P; Vaag, A

    2002-01-01

    of triglyceride (P = 0.04) and insulin (P = 0.02) and lower levels of HDL-cholesterol (P = 0.04). CONCLUSION: The T-allele of the codon 2488 polymorphism influenced parameters related to the insulin resistance syndrome, i.e. increased levels of insulin, increased levels of triglyceride and decreased levels of HDL...

  14. Association of the p53 codon 72 polymorphism to gastric cancer risk in a high risk population of Costa Rica

    International Nuclear Information System (INIS)

    Alpizar-Alpizar, Warner; Sierra, Rafaela; Cuenca, Patricia; Une, Clas; Mena, Fernando; Perez-Perez, Guillermo Ignacio

    2005-01-01

    Gastric cancer is the second most common cancer associated death cause worldwide. Several factors have been associated with higher risk to develop gastric cancer, among them genetic predisposition. The p53 gene has a polymorphism located at codon 72, which has been associated with higher risk of several types of cancer, including gastric cancer. The aim of this study was to determine the association of p53, codon 72 polymorphism, with the risk of gastric cancer and pre-malignant lesions in a high-risk population from Costa Rica. The genotyping was carried out by PCR-RFLP in a sample of 58 gastric cancer patients, 99 control persons and 41 individuals classified as group I and II, according to the Japanese histological classification. No association was found for p53, codon 72 polymorphism with neither the risk of gastric cancer nor the risk of less severe gastric lesions in the studied sample. Based on this study and taking into account other studies carried out with p53, codon 72 polymorphism, the role of this polymorphism in the development of gastric cancer remains unclear. De novo mutations on p53 gene produced during neoplastic development of this disease might play a greater role than germinal polymorphisms of this same gene. Other polymorphic genes have been associated with higher risk to develop gastric cancer. (author) [es

  15. Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Zedenius, J.; Svensson, A.; Baeckdahl, M.; Wallin, G. [Karolinska Hospital, Stockholm (Sweden)] [and others

    1995-10-01

    The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and has in a previous study been correlated with a less favorable clinical outcome. In the present study, 46 MTCs were selected for investigation of the codon 918 mutation. The mutation was found in 29 tumors (63%), and was significantly correlated with a poor outcome, with regard to distant metastasis or tumor recurrence (p<10{sup 4}). Two tumors showed multifocal growth and C-cell hyperplasia, and these patients were therefore also investigated for germline mutations in exons 10, 11 and 16. The codon 918 mutation was found only in the tumors, thus of somatic origin. The RET codon 918 mutation may have prognostic impact, and therefore preoperative assessment may influence decision-making in the treatment of patients suffering from MTC. 13 refs., 1 fig., 1 tab.

  16. TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development

    Science.gov (United States)

    Volodko, Natalia; Salla, Mohamed; Eksteen, Bertus; Fedorak, Richard N; Huynh, Hien Q; Baksh, Shairaz

    2015-01-01

    AIM: To investigate the association between tumor protein 53 (TP53) codon 72 polymorphisms and the risk for inflammatory bowel disease (IBD) development. METHODS: Numerous genetic and epigenetic drivers have been identified for IBD including the TP53 gene. Pathogenic mutations in TP53 gene have only been reported in 50% of colorectal cancer (CRC) patients. A single nucleotide polymorphism (SNP) in the TP53 gene resulting in the presence of either arginine (Arg) or proline (Pro) or both at codon 72 was shown to alter TP53 tumor-suppressor properties. This SNP has been investigated as a risk factor for numerous cancers, including CRC. In this study we analyzed TP53 codon 72 polymorphism distribution in 461 IBD, 181 primary sclerosing cholangitis patients and 62 healthy controls. Genotyping of TP53 was performed by sequencing and restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood. RESULTS: The most frequent TP53 genotype in IBD patients was Arg/Arg occurring in 54%-64% of cases (and in only 32% of controls). Arg/Pro was the most prevalent genotype in controls (53%) and less common in patients (31%-40%). Pro/Pro frequency was not significantly different between controls and IBD patients. CONCLUSION: The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development. PMID:26420962

  17. Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma

    Science.gov (United States)

    Prevost, Luanna B.; Smith, Michelle K.; Knight, Jennifer K.

    2016-01-01

    Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon…

  18. Codon modification for the DNA sequence of a single-chain Fv antibody against clenbuterol and expression in Pichia pastoris

    Science.gov (United States)

    To improve expression efficiency of the recombinant single-chain variable fragment (scFv) against clenbuterol (CBL) obtained from mouse in the methylotrophic yeast Pichia pastoris (P. pastoris) GS115, the DNA sequence encoding for CBL-scFv was designed and synthesized based on the codon bias of P. p...

  19. Kissing loops hide premature termination codons in pre-mRNAof selenoprotein genes and in genes containing programmedribosomal frameshifts

    DEFF Research Database (Denmark)

    Knudsen, Steen; Brunak, Søren

    1997-01-01

    A novel RNA secondary structure that places the selenocysteine codon UGA in one hairpin and a donor splice site in another, has been discovered in selenoprotein genes. The presence of the structure resolves the discrepancy that the selenocysteine triplet, UGA, should block splicing. Without a spe...

  20. Human immunodeficiency virus fitness in vivo: calculations based on a single zidovudine resistance mutation at codon 215 of reverse transcriptase

    NARCIS (Netherlands)

    Goudsmit, J.; de Ronde, A.; Ho, D. D.; Perelson, A. S.

    1996-01-01

    We monitored a subject newly infected with a zidovudine-resistant human immunodeficiency virus type 1 strain and found that in the absence of drug, the viral population with the resistance-conferring tyrosine (TAC) codon 215 of reverse transcriptase was gradually replaced. By using standard formulas

  1. Glutathione S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in human tumor cells.

    Science.gov (United States)

    Ueda, Masatsugu; Hung, Yao-Ching; Terai, Yoshito; Kanda, Koji; Takehara, Mikio; Yamashita, Hikari; Yamaguchi, Hiroyuki; Akise, Daisuke; Yasuda, Masayuki; Nishiyama, Koji; Ueki, Minoru

    2003-12-01

    The genes of the glutathione S-transferase (GST) family encode enzymes that appear to be critical in cellular protection against the cytotoxic effects, whereas p53 is a tumor suppressor gene. Despite a large number of studies on germline polymorphisms of GSTM1, GSTT1 and p53 genes, there have been very few reports on genotyping of these genes in human malignant tumor cells. In this study, we investigated GSTM1, GSTT1 and p53 codon 72 polymorphisms in a variety of human tumor cell lines originating from different organs to clarify tissue-specific polymorphic frequency of these genes in human solid tumors. The GSTM1 and GSTT1 genetic polymorphisms were evaluated using multiplex PCR techniques and PCR-RFLP analysis was conducted to identify p53 codon 72 genotypes. Gene expression of GSTM1 or GSTT1 was detected by RT-PCR in the cells with respective present genotype for each. Polymorphisms of p53 codon 72 detected by PCR-RFLP were also confirmed using SSCP and sequence analyses. GSTM1 and GSTT1 genotypes were various in 104 cell lines examined. Null GSTM1 genotype was dominant in small cell lung, kidney and ovarian carcinoma cells, whereas null GSTT1 genotype was dominant in cervical and endometrial carcinoma cells. GSTM1 and GSTT1 genotypes in ovarian carcinoma cells were quite similar to those in small cell lung carcinoma cells. Polymorphic frequency of p53 codon 72 was also various among the cells, however, the Pro allele was found in only 1 of 6 kidney, 14 cervical and 4 endometrial carcinoma cell lines. There was a significant difference in GSTM1 and p53 genotypes between 34 small cell and 24 non small cell lung carcinoma cells (P p53 genotypes revealed that null GSTM1 genotype was associated with the Arg allele of p53 codon 72 in 58 lung carcinoma cells and null GSTT1 genotype was associated with the Pro/Pro homozygote in 104 tumor cell lines examined. This is the first study examining GSTM1, GSTT1 and p53 codon 72 polymorphisms in a variety of human solid tumor

  2. Preferences of AAA/AAG codon recognition by modified nucleosides, τm5s2U34 and t6A37 present in tRNALys.

    Science.gov (United States)

    Sonawane, Kailas D; Kamble, Asmita S; Fandilolu, Prayagraj M

    2017-12-27

    Deficiency of 5-taurinomethyl-2-thiouridine, τm 5 s 2 U at the 34th 'wobble' position in tRNA Lys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNA Lys , recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNA Lys in presence and absence of τm 5 s 2 U 34 and N 6 -threonylcarbamoyl adenosine (t 6 A 37 ) along with AAA and AAG codons have been accomplished. Additional four MD simulations of multiple ASL mt tRNA Lys models in the context of ribosomal A-site residues have also been performed to investigate the role of A-site in recognition of AAA/AAG codons. MD simulation results show that, ASL models in presence of τm 5 s 2 U 34 and t 6 A 37 with codons AAA/AAG are more stable than the ASL lacking these modified bases. MD trajectories suggest that τm 5 s 2 U recognizes the codons initially by 'wobble' hydrogen bonding interactions, and then tRNA Lys might leave the explicit codon by a novel 'single' hydrogen bonding interaction in order to run the protein biosynthesis process smoothly. We propose this model as the 'Foot-Step Model' for codon recognition, in which the single hydrogen bond plays a crucial role. MD simulation results suggest that, tRNA Lys with τm 5 s 2 U and t 6 A recognizes AAA codon more preferably than AAG. Thus, these results reveal the consequences of τm 5 s 2 U and t 6 A in recognition of AAA/AAG codons in mitochondrial disease, MERRF.

  3. Calcitonin receptor gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis in South Indian population – An observational study

    Directory of Open Access Journals (Sweden)

    Anuradha Ankam

    2017-01-01

    Full Text Available Context: Chronic periodontitis and osteoporosis are multifactorial diseases which share common risk factors. Interactions between genetic and other factors determine the likely hood of osteoporotic fractures and chronic periodontitis. Calcitonin receptor (CTR gene polymorphism is one of the important factors which contribute to the development of osteoporosis and chronic periodontitis. Aims: This study highlights the association of CTR gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis and healthy controls in south Indian population. Settings and Design: The study was designed as a case–control retrospective, observational clinical trial which was conducted to assess the role of CTR gene polymorphism in patients with osteoporosis and periodontitis as well as in healthy controls. Materials and Methods: A total of 50 subjects were taken into the study comprising of 20 healthy and 30 osteoporotic subjects with chronic periodontitis between the age group of 30–55 years. Within the limitations of our study, only 50 subjects were taken in the study due to the strict sampling method (Patients who were just diagnosed with osteoporosis and periodontitis and hence not taking any medication. 2 ml of blood sample was collected in ethylenediamine tetra acetic acid containing vials, and polymerase chain reaction was run to identify CTR gene polymorphism. Statistical Analysis Used: Statistical analysis was done by student t-test. Pertaining to C > T allele pattern there was a significant difference between the test and control group. Results: A significant difference was observed between the test and control group in relation to the C > T allele pattern. Patients showing TT genotype distribution had greater periodontal destruction and lower bone-mineral density compared to CT genotype distribution followed by CC genotype distribution indicating TT homozygotes are more prone to the development of osteoporosis with

  4. The silent codon change I507-ATC->ATT contributes to the severity of the ΔF508 CFTR channel dysfunction.

    Science.gov (United States)

    Lazrak, Ahmed; Fu, Lianwu; Bali, Vedrana; Bartoszewski, Rafal; Rab, Andras; Havasi, Viktoria; Keiles, Steve; Kappes, John; Kumar, Ranjit; Lefkowitz, Elliot; Sorscher, Eric J; Matalon, Sadis; Collawn, James F; Bebok, Zsuzsanna

    2013-11-01

    The most common disease-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is the out-of-frame deletion of 3 nucleotides (CTT). This mutation leads to the loss of phenylalanine-508 (ΔF508) and a silent codon change (SCC) for isoleucine-507 (I507-ATC→ATT). ΔF508 CFTR is misfolded and degraded by endoplasmic reticulum-associated degradation (ERAD). We have demonstrated that the I507-ATC→ATT SCC alters ΔF508 CFTR mRNA structure and translation dynamics. By comparing the biochemical and functional properties of the I507-ATT and I507-ATC ΔF508 CFTR, we establish that the I507-ATC→ATT SCC contributes to the cotranslational misfolding, ERAD, and to the functional defects associated with ΔF508 CFTR. We demonstrate that the I507-ATC ΔF508 CFTR is less susceptible to the ER quality-control machinery during translation than the I507-ATT, although 27°C correction is necessary for sufficient cell-surface expression. Whole-cell patch-clamp recordings indicate sustained, thermally stable cAMP-activated Cl(-) transport through I507-ATC and unstable function of the I507-ATT ΔF508 CFTR. Single-channel recordings reveal improved gating properties of the I507-ATC compared to I507-ATT ΔF508 CFTR (NPo=0.45±0.037 vs. NPo=0.09±0.002; P<0.001). Our results signify the role of the I507-ATC→ATT SCC in the ΔF508 CFTR defects and support the importance of synonymous codon choices in determining the function of gene products.

  5. Empirical Productivity Indices and Indicators

    NARCIS (Netherlands)

    B.M. Balk (Bert)

    2016-01-01

    textabstractThe empirical measurement of productivity change (or difference) by means of indices and indicators starts with the ex post profit/loss accounts of a production unit. Key concepts are profit, leading to indicators, and profitability, leading to indices. The main task for the productivity

  6. [Creation of DNA vaccine vector based on codon-optimized gene of rabies virus glycoprotein (G protein) with consensus amino acid sequence].

    Science.gov (United States)

    Starodubova, E S; Kuzmenko, Y V; Latanova, A A; Preobrazhenskaya, O V; Karpov, V L

    2016-01-01

    An optimized design of the rabies virus glycoprotein (G protein) for use within DNA vaccines has been suggested. The design represents a territorially adapted antigen constructed taking into account glycoprotein amino acid sequences of the rabies viruses registered in the Russian Federation and the vaccine Vnukovo-32 strain. Based on the created consensus amino acid sequence, the nucleotide codon-optimized sequence of this modified glycoprotein was obtained and cloned into the pVAX1 plasmid (a vector of the last generation used in the creation of DNA vaccines). A twofold increase in this gene expression compared to the expression of the Vnukovo-32 strain viral glycoprotein gene in a similar vector was registered in the transfected cell culture. It has been demonstrated that the accumulation of modified G protein exceeds the number of the control protein synthesized using the plasmid with the Vnukovo-32 strain viral glycoprotein gene by 20 times. Thus, the obtained modified rabies virus glycoprotein can be considered to be a promising DNA vaccine antigen.

  7. Waste indicators

    International Nuclear Information System (INIS)

    Dall, O.; Lassen, C.; Hansen, E.

    2003-01-01

    The Waste Indicator Project focuses on methods to evaluate the efficiency of waste management. The project proposes the use of three indicators for resource consumption, primary energy and landfill requirements, based on the life-cycle principles applied in the EDIP Project. Trial runs are made With the indicators on paper, glass packaging and aluminium, and two models are identified for mapping the Danish waste management, of which the least extensive focuses on real and potential savings. (au)

  8. Waste indicators

    Energy Technology Data Exchange (ETDEWEB)

    Dall, O.; Lassen, C.; Hansen, E. [Cowi A/S, Lyngby (Denmark)

    2003-07-01

    The Waste Indicator Project focuses on methods to evaluate the efficiency of waste management. The project proposes the use of three indicators for resource consumption, primary energy and landfill requirements, based on the life-cycle principles applied in the EDIP Project. Trial runs are made With the indicators on paper, glass packaging and aluminium, and two models are identified for mapping the Danish waste management, of which the least extensive focuses on real and potential savings. (au)

  9. Quality indicators

    DEFF Research Database (Denmark)

    Hjorth-Andersen, Christian

    1991-01-01

    In recent literature it has been suggested that consumers need have no knowledge of product quality as a number of quality indicators (or signals) may be used as substitutes. Very little attention has been paid to the empirical verification of these studies. The present paper is devoted...... to the issue of how well these indicators perform, using market data provided by consumer magazines from 3 countries. The results strongly indicate that price is a poor quality indicator. The paper also presents some evidence which suggests that seller reputation and easily observable characteristics are also...

  10. 19F NMR studies of 5-fluorouracil-substituted Escherichia coli transfer RNAs: solution structure and codon-anticodon interaction

    International Nuclear Information System (INIS)

    Gollnick, P.D.

    1986-01-01

    19 F NMR was used to study E. coli tRNA 1 /sup Val/, tRNA/sub f//sup Met/, and tRNA/sub m//Met/, in which 5-fluorouracil (FUra) has replaced uracil and uracil-derived minor bases. 19 F NMR spectra of these tRNAs resolve resonances from nearly all the incorporated FUra residues. Each of the three tRNAs can be resolved into two isoaccepting species, termed forms A and B, whose 19 F spectra differ in the shift of one 19 F peak from ca. 4.5 ppm in form B, upfield to -15 ppm in form A. Because the two isoacceptors of each tRNA differ only at one position, the peaks at 4.5 ppm in the spectra of (FUra)tRNA 1 /sup Val/ and (FUra)tRNA/sub m//sup Met/; are assigned to FUra 17 and Fura 20 respectively. Bisulfate modification and pH dependence indicate that 19 F signals in the central region of the spectrum of (FUra)tRNA 1 /sup Val/ correspond to fluorouracils in non-base-paired regions. Photoreaction with psoralen indicates upfield 19 F signals arise from residues in helical environments. Removal of magnesium or addition of NaCl produces major, reversible changes in the 19 F spectrum of fluorinated tRNAs. Studies of manganese and spermine binding to (FUra)tRNA 1 /sup Val/ allow localization of several resonances in the 18 F spectrum to regions near putative binding sites for these ions. Binding of the codon G/sub p/U/sub p/A causes an upfield shift of a 19 F resonance at 3.9 ppm in the spectrum of (FUra)tRNA 1 /sup Val/. G/sub p/U/sub p/A/sub p/A, which is complementary to the anticodon and 5'-adjacent FUra 33, shifts an additional 19 F peak at 4.5 ppm. 1 H NMR and RNase H digestion studies show that the oligonucleotides bind to the anticodon

  11. Codon optimization of the human papillomavirus E7 oncogene induces a CD8+ T cell response to a cryptic epitope not harbored by wild-type E7.

    Directory of Open Access Journals (Sweden)

    Felix K M Lorenz

    Full Text Available Codon optimization of nucleotide sequences is a widely used method to achieve high levels of transgene expression for basic and clinical research. Until now, immunological side effects have not been described. To trigger T cell responses against human papillomavirus, we incubated T cells with dendritic cells that were pulsed with RNA encoding the codon-optimized E7 oncogene. All T cell receptors isolated from responding T cell clones recognized target cells expressing the codon-optimized E7 gene but not the wild type E7 sequence. Epitope mapping revealed recognition of a cryptic epitope from the +3 alternative reading frame of codon-optimized E7, which is not encoded by the wild type E7 sequence. The introduction of a stop codon into the +3 alternative reading frame protected the transgene product from recognition by T cell receptor gene-modified T cells. This is the first experimental study demonstrating that codon optimization can render a transgene artificially immunogenic through generation of a dominant cryptic epitope. This finding may be of great importance for the clinical field of gene therapy to avoid rejection of gene-corrected cells and for the design of DNA- and RNA-based vaccines, where codon optimization may artificially add a strong immunogenic component to the vaccine.

  12. High-resolution melting analysis of gyrA codon 84 and grlA codon 80 mutations conferring resistance to fluoroquinolones in Staphylococcus pseudintermedius isolates from canine clinical samples.

    Science.gov (United States)

    Loiacono, Monica; Martino, Piera A; Albonico, Francesca; Dell'Orco, Francesca; Ferretti, Manuela; Zanzani, Sergio; Mortarino, Michele

    2017-09-01

    Staphylococcus pseudintermedius is an opportunistic pathogen of dogs and cats. A high-resolution melting analysis (HRMA) protocol was designed and tested on 42 clinical isolates with known fluoroquinolone (FQ) susceptibility and gyrA codon 84 and grlA codon 80 mutation status. The HRMA approach was able to discriminate between FQ-sensitive and FQ-resistant strains and confirmed previous reports that the main mutation site associated with FQ resistance in S. pseudintermedius is located at position 251 (Ser84Leu) of gyrA. Routine, HRMA-based FQ susceptibility profiles may be a valuable tool to guide therapy. The FQ resistance-predictive power of the assay should be tested in a significantly larger number of isolates.

  13. Codon Optimization Leads to Functional Impairment of RD114-TR Envelope Glycoprotein

    Directory of Open Access Journals (Sweden)

    Eleonora Zucchelli

    2017-03-01

    Full Text Available Lentiviral vectors (LVs are a highly valuable tool for gene transfer currently exploited in basic, applied, and clinical studies. Their optimization is therefore very important for the field of vectorology and gene therapy. A key molecule for LV function is the envelope because it guides cell entry. The most commonly used in transiently produced LVs is the vesicular stomatitis virus glycoprotein (VSV-G envelope, whose continuous expression is, however, toxic for stable LV producer cells. In contrast, the feline endogenous retroviral RD114-TR envelope is suitable for stable LV manufacturing, being well tolerated by producer cells under constitutive expression. We have previously reported successful, transient and stable production of LVs pseudotyped with RD114-TR for good transduction of T lymphocytes and CD34+ cells. To further improve RD114-TR-pseudotyped LV cell entry by increasing envelope expression, we codon-optimized the RD114-TR open reading frame (ORF. Here we show that, despite the RD114-TRco precursor being produced at a higher level than the wild-type counterpart, it is unexpectedly not duly glycosylated, exported to the cytosol, and processed. Correct cleavage of the precursor in the functional surface and transmembrane subunits is prevented in vivo, and, consequently, the unprocessed precursor is incorporated into LVs, making them inactive.

  14. Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis.

    Science.gov (United States)

    Aslam, Aisha A; Higgins, Colin; Sinha, Ian P; Southern, Kevin W

    2017-01-19

    Cystic fibrosis is a common life-shortening genetic disorder in the Caucasian population (less common in other ethnic groups) caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces and the mutation most notably affects the airways. In the lungs of people with cystic fibrosis, defective protein results in a dehydrated surface liquid and compromised mucociliary clearance. The resulting thick mucus makes the airway prone to chronic infection and inflammation, which consequently damages the structure of the airways, eventually leading to respiratory failure. Additionally, abnormalities in the cystic fibrosis transmembrane conductance regulator protein lead to other systemic complications including malnutrition, diabetes and subfertility.Five classes of mutation have been described, depending on the impact of the mutation on the processing of the cystic fibrosis transmembrane conductance regulator protein in the cell. In class I mutations, the presence of premature termination codons prevents the production of any functional protein resulting in a severe cystic fibrosis phenotype. Advances in the understanding of the molecular genetics of cystic fibrosis has led to the development of novel mutation-specific therapies. Therapies targeting class I mutations (premature termination codons) aim to mask the abnormal gene sequence and enable the normal cellular mechanism to read through the mutation, potentially restoring the production of the cystic fibrosis transmembrane conductance regulator protein. This could in turn make salt transport in the cells function more normally and may decrease the chronic infection and inflammation that characterises lung disease in people with cystic fibrosis. To evaluate the benefits and harms of ataluren and similar compounds on clinically important outcomes in people with

  15. A Codon Deletion at the Beginning of Green Fluorescent Protein Genes Enhances Protein Expression.

    Science.gov (United States)

    Rodríguez-Mejía, José-Luis; Roldán-Salgado, Abigail; Osuna, Joel; Merino, Enrique; Gaytán, Paul

    2017-01-01

    Recombinant protein expression is one of the key issues in protein engineering and biotechnology. Among the different models for assessing protein production and structure-function studies, green fluorescent protein (GFP) is one of the preferred models because of its importance as a reporter in cellular and molecular studies. In this research we analyze the effect of codon deletions near the amino terminus of different GFP proteins on fluorescence. Our study includes Gly4 deletions in the enhanced GFP (EGFP), the red-shifted GFP and the red-shifted EGFP. The Gly4 deletion mutants and their corresponding wild-type counterparts were transcribed under the control of the T7 or Trc promoters and their expression patterns were analyzed. Different fluorescent outcomes were observed depending on the type of fluorescent gene versions. In silico analysis of the RNA secondary structures near the ribosome binding site revealed a direct relationship between their minimum free energy and GFP production. Integrative analysis of these results, including SDS-PAGE analysis, led us to conclude that the fluorescence improvement of cells expressing different versions of GFPs with Gly4 deleted is due to an enhancement of the accessibility of the ribosome binding site by reducing the stability of the RNA secondary structures at their mRNA leader regions. © 2016 S. Karger AG, Basel.

  16. Alteration of the ATG start codon of the A* protein of bacteriophage [phi]X174 into an ATT codon yields a viable phage indicating that A* protein is not essential for [phi]X174 reproduction

    NARCIS (Netherlands)

    Baas, P.D.; Liewerink, H.; Teeffelen, H.A.A.M. van; Mansfeld, A.D.M. van; Boom, J.M. van; Jansz, H.S.

    1987-01-01

    Bacteriophage X174 gene A encodes two proteins: the gene A protein and the smaller A* protein, which is synthesized from a translational start signal within the A gene in the same reading frame as the gene A protein. The gene A protein is involved in initiation, elongation and termination of rolling

  17. Serial MRI in early Creutzfeldt-Jacob disease with a point mutation of prion protein at codon 180

    International Nuclear Information System (INIS)

    Ishida, S.; Sugino, M.; Shinoda, K.; Ohsawa, N.; Koizumi, N.; Ohta, T.; Kitamoto, T.; Tateishi, J.

    1995-01-01

    We report a 66-year-old woman with histologically diagnosed Creutzfeld-Jacob disease (CJD), followed with MRI from an early clinical stage. MRI demonstrated expansion of the high cortical signal on T2-weighted images, which differs from previous MRI reports of CJD. This patient followed an atypical clinical course: 16 months had passed before she developed akinetic mutism, and periodic sharp waves had not been detected on EEG after 2 years in spite of her akinetic mutism. Brain biopsy showed primary spongiform changes in the grey matter, and a point mutation of the prion protein gene at codon 180 was discovered using polymerase chain reaction direct sequencing and Tth 111 I cutting. This is the first case with the point mutation of the codon 180 variant with an atypical clinical course and characteristic MRI findings. (orig.)

  18. Solar Indices

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Collection includes a variety of indices related to solar activity contributed by a number of national and private solar observatories located worldwide. This...

  19. Geographical Indications

    OpenAIRE

    Anechitoae Constantin; Grigoru? Lavinia-Maria

    2011-01-01

    “The denomination of origin” may be the name of a region, a specific place or country used to describe an agricultural or food product. "The geographical indication" may be the name of a region, a specific place or a country, used to describe an agricultural or food product. The indication of provenance and the denomination of origin serve to identify the source and origin of goods or services.

  20. p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinomas in China.

    Science.gov (United States)

    Li, Tao; Lu, Zhe-Ming; Guo, Mei; Wu, Qin-Jiao; Chen, Ke-Neng; Xing, Hai-Ping; Mei, Qiang; Ke, Yang

    2002-12-15

    Human papillomavirus (HPV) plays an important role in the development of carcinomas at various body sites. It was found previously that the p53 codon 72 polymorphism (C/G) is a high-risk factor for the development HPV-associated cervical carcinoma. However, it still was considered controversial in several studies of cervical and esophageal carcinoma. In the current study, the authors used an allele specific polymerase chain reaction (PCR) method to analyze correlation between the p53 codon 72 (C/G) polymorphism and HPV-associated, noncancerous esophageal epithelium as well as esophageal, ovarian, and breast carcinoma in the Chinese population. Esophageal balloon cytology examination samples were obtained from high-incidence and low-incidence populations for esophageal carcinoma in Anyang (Henan Province). Thirty-six of 48 esophageal balloon samples from the high-incidence population were HPV positive, and 13 of 33 esophageal balloon samples from the low-incidence population were HPV positive. Thirty-nine of 62 esophageal carcinoma samples from Anyang Tumor Hospital were HPV positive. Twenty-six of 39 ovarian carcinoma samples from the Second Affiliated Hospital of Inner Mongolia Medical College were HPV positive. Nineteen of 82 breast carcinoma samples from Beijing Cancer Hospital were HPV positive. It is noteworthy that the distribution of the p53 codon 72 Arg homozygous genotype in HPV positive samples of esophageal epithelium, ovarian carcinoma, and breast carcinoma was significantly higher compared with HPV negative tumor samples. (P p53 codon 72 Arg homozygous genotype is one of the high-risk genetic factors for HPV-associated malignancies among the Chinese population. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.11008

  1. The highly conserved codon following the slippery sequence supports -1 frameshift efficiency at the HIV-1 frameshift site.

    Directory of Open Access Journals (Sweden)

    Suneeth F Mathew

    Full Text Available HIV-1 utilises -1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating -1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the 'intercodon' contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules-eRF1 protein or a cognate suppressor tRNA-were able to access and decode the intercodon prior to -1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.

  2. Fuzzy clustering demonstrates that codon 72 SNP rs1042522 of TP53 gene associated with HNSCC but not with prognoses.

    Science.gov (United States)

    Pinheiro, Ugo Borges; Fraga, Carlos Alberto de Carvalho; Mendes, Danilo Cangussu; Farias, Lucyana Conceição; Cardoso, Cláudio Marcelo; Silveira, Christine Mendes; D'Angelo, Marcos Flávio Silveira Vasconcelos; Jones, Kimberly Marie; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

    2015-12-01

    It is estimated that 7.6 million people will die as a consequence of head and neck squamous cell carcinoma (HNSCC). Genetic predisposition has emerged as an important risk factor in the development and prognosis of HNSCC. Considering this, the aim of the current study is to assess whether codon 72 SNP of the TP53 gene (rs1042522) is associated with an increased odds ratio of developing HNSCC or with a worse prognosis in patients with HNSCC. Analysis of the rs1042522 in HNSCC patients and in control individuals. Differences between the case and control groups were determined using chi-squared tests. Multivariate analysis was performed to evaluate the odds ratio of HNSCC. Fussy C Means Clustering was to cluster HNSCC patients for survival analyses. Time of survival was calculated using the Kaplan-Meier estimator and comparing this to the log rank test. Statistical significance was set at p control group. Logistic regression demonstrated that the Arg/Arg genotype, smoking, and alcohol consumption increase the odds ratio of HNSCC. No association between TP53 codon 72 polymorphism and P53 expression. No association between rs1042522 and survival or prognoses was observed. This study identified that individuals carrying the arginine allele at rs1042522 have an increased odds ratio of HNSCC. However, no association between codon 72 SNP of the TP53 gene and HNSCC prognosis or P53 expression was observed.

  3. [Risk factors for cervico-uterine cancer associated to HPV: p53 codon 72 polymorphism in women attending hospital care].

    Science.gov (United States)

    Sifuentes Alvarez, A; Reyes Romero, Miguel

    2003-01-01

    In codon 72 of the p53 antioncogene there are two alleles, arginine and proline; the arg/arg genotype has recently been identified as a risk factor for developing of cervicouterine cancer (CuCa) associated to human papillomavirus (HVP) infection. The aim of this work was to determine in a sample of women the frequency of proline-arginine alleles and genotypes of p53 codon 72. The study was conducted in a sample of inpatient women at the hospital. p53 codon 72 alleles were determined in genomic ADN by amplification of specific sequences by chi 2 test. From 102 analyzed samples, p53-arginine allele corresponded to 67.64% and p53-proline allele corresponded to 32.36%; 47 women (46.10%) were arg/arg homocygotes, 11 women (10.77%) were pro/pro homocygotes, 44 women (43.13%) were arg/pro heterocigotes; the genotype distribution was within the Hardy-Weinberg equilibrium. The detection of a high percentage of arginine homocygotes suggests that this genotype, considered as a risk factor for cancer associated to oncogenic HPV, has a high prevalence in the north of Mexico. The determination of this kind of polymorphisms is important as preventive action with regard to identification of risk factors for CaCu associated to HPV infection.

  4. Synonymous codon usage bias in plant mitochondrial genes is associated with intron number and mirrors species evolution.

    Directory of Open Access Journals (Sweden)

    Wenjing Xu

    Full Text Available 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.

  5. Investigation of p53 codon72 polymorphism in oral squamous cell carcinoma (SCC specimens and normal population by PCR

    Directory of Open Access Journals (Sweden)

    Deyhimi P.

    2008-10-01

    Full Text Available "nBackground and Aim: A single nucleotide polymorphism at codon 72 of the p53 gene alters the p53 protein structure and affects its activity. This polymorphism depends on geographic regions and race. Also its association with some cancers has been reported. The aim of this study was to investigate this polymorphism in well differentiated oral SCC and normal population in the city of Isfahan. "nMaterials and Methods: In this case-control study, 20 paraffin blocks of non metastatic and well differentiated oral SCC were selected from the archive of oral pathology department of dental school between 2001 and 2005. 20 whole blood samples from normal people were considered as control group. After DNA extraction, p53 codon 72 polymorphism was determined by polymerase chain reaction (PCR technique using specific primers of Arg and Pro and agarose gel electrophoresis. Data were analyzed by Fisher's exact test with p<0.05 as the level of significance. "nResults: The prevalence of Arg/Arg , Arg/Pro and Pro/Pro genotypes in case group were 45%,45% and 10% respectively compared to 45%,50% and 5% in controls. There was no statistical significant difference in p53 codon 72 genotypes distribution between case and control groups. "nConclusion: Based on the results of this study, p53 polymorphism could not be considered as a genetic predisposing factor for oral SCC development in Isfahan.

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

    Directory of Open Access Journals (Sweden)

    T Kunisawa

    2006-01-01

    Full Text Available Complete genomic sequence data are stored in the public GenBank/EMBL/DDBJ databases so that any investigator can make use of the data. This report describes a comparative analysis of codon usage that is impossible without such a public and open data system. A limited number of bacteriophages harbor their own transfer RNAs. Based on a comparison between T4 phage-encoded tRNA species and the relative cellular amounts of host Escherichia coli tRNAs, it is hypothesized that T4 tRNAs could serve to supplement host isoacceptor tRNA species that are present in minor amounts and thus enhance the translational efficiency of phage proteins. When compared to their respective host bacteria, the codon usage data of bacteriophages D3, φC31, HP1, D29 and 933W all show an increased frequency of synonymous codons or amino acids that correspond to phage tRNA species, suggesting their supplemental role in the efficient production of phage proteins. The data-analysis presents an example in which the availability of an open and fully accessible database system would allow one to obtain comprehensive insights into a fundamental problem in molecular biology.

  7. Calculating site-specific evolutionary rates at the amino-acid or codon level yields similar rate estimates

    Directory of Open Access Journals (Sweden)

    Dariya K. Sydykova

    2017-05-01

    Full Text Available Site-specific evolutionary rates can be estimated from codon sequences or from amino-acid sequences. For codon sequences, the most popular methods use some variation of the dN∕dS ratio. For amino-acid sequences, one widely-used method is called Rate4Site, and it assigns a relative conservation score to each site in an alignment. How site-wise dN∕dS values relate to Rate4Site scores is not known. Here we elucidate the relationship between these two rate measurements. We simulate sequences with known dN∕dS, using either dN∕dS models or mutation–selection models for simulation. We then infer Rate4Site scores on the simulated alignments, and we compare those scores to either true or inferred dN∕dS values on the same alignments. We find that Rate4Site scores generally correlate well with true dN∕dS, and the correlation strengths increase in alignments with greater sequence divergence and more taxa. Moreover, Rate4Site scores correlate very well with inferred (as opposed to true dN∕dS values, even for small alignments with little divergence. Finally, we verify this relationship between Rate4Site and dN∕dS in a variety of empirical datasets. We conclude that codon-level and amino-acid-level analysis frameworks are directly comparable and yield very similar inferences.

  8. Efficient Coproduction of Mannanase and Cellulase by the Transformation of a Codon-Optimized Endomannanase Gene from Aspergillus niger into Trichoderma reesei.

    Science.gov (United States)

    Sun, Xianhua; Xue, Xianli; Li, Mengzhu; Gao, Fei; Hao, Zhenzhen; Huang, Huoqing; Luo, Huiying; Qin, Lina; Yao, Bin; Su, Xiaoyun

    2017-12-20

    Cellulase and mannanase are both important enzyme additives in animal feeds. Expressing the two enzymes simultaneously within one microbial host could potentially lead to cost reductions in the feeding of animals. For this purpose, we codon-optimized the Aspergillus niger Man5A gene to the codon-usage bias of Trichoderma reesei. By comparing the free energies and the local structures of the nucleotide sequences, one optimized sequence was finally selected and transformed into the T. reesei pyridine-auxotrophic strain TU-6. The codon-optimized gene was expressed to a higher level than the original one. Further expressing the codon-optimized gene in a mutated T. reesei strain through fed-batch cultivation resulted in coproduction of cellulase and mannanase up to 1376 U·mL -1 and 1204 U·mL -1 , respectively.

  9. Operational indicators

    International Nuclear Information System (INIS)

    2010-01-01

    The chapter presents the operational indicators related to budget, travel costs and tickets, the evolution of the annual program for regulatory inspection, the scientific production, requested patents and the numbers related to the production of the services offered by the Institution

  10. Anthropometric indices

    DEFF Research Database (Denmark)

    Oguoma, V. M.; Nwose, E. U.; Skinner, T. C.

    2016-01-01

    BACKGROUND: The current anthropometric indices used for diagnosis of cardio-metabolic syndrome (CMS) in sub-Saharan Africa are those widely validated in the western world. We hereby aim to compare the sensitivity and specificity of these tools in identifying risk factors for CMS. METHOD: The study...

  11. TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

    Directory of Open Access Journals (Sweden)

    M.A.C. Smith

    2007-11-01

    Full Text Available TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72 polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia, and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg = 0.69 and P (Pro = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.

  12. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...

  13. Adaptive Patterns of Mitogenome Evolution Are Associated with the Loss of Shell Scutes in Turtles.

    Science.gov (United States)

    Escalona, Tibisay; Weadick, Cameron J; Antunes, Agostinho

    2017-10-01

    The mitochondrial genome encodes several protein components of the oxidative phosphorylation (OXPHOS) pathway and is critical for aerobic respiration. These proteins have evolved adaptively in many taxa, but linking molecular-level patterns with higher-level attributes (e.g., morphology, physiology) remains a challenge. Turtles are a promising system for exploring mitochondrial genome evolution as different species face distinct respiratory challenges and employ multiple strategies for ensuring efficient respiration. One prominent adaptation to a highly aquatic lifestyle in turtles is the secondary loss of keratenized shell scutes (i.e., soft-shells), which is associated with enhanced swimming ability and, in some species, cutaneous respiration. We used codon models to examine patterns of selection on mitochondrial protein-coding genes along the three turtle lineages that independently evolved soft-shells. We found strong evidence for positive selection along the branches leading to the pig-nosed turtle (Carettochelys insculpta) and the softshells clade (Trionychidae), but only weak evidence for the leatherback (Dermochelys coriacea) branch. Positively selected sites were found to be particularly prevalent in OXPHOS Complex I proteins, especially subunit ND2, along both positively selected lineages, consistent with convergent adaptive evolution. Structural analysis showed that many of the identified sites are within key regions or near residues involved in proton transport, indicating that positive selection may have precipitated substantial changes in mitochondrial function. Overall, our study provides evidence that physiological challenges associated with adaptation to a highly aquatic lifestyle have shaped the evolution of the turtle mitochondrial genome in a lineage-specific manner. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Terminologie des indices boursiers

    OpenAIRE

    Van der Yeught, Michel

    2013-01-01

    Les indices boursiers sont omniprésents en anglais financier. Les plus importants sont universellement familiers mais leur nature et leur fonctionnement restent largement méconnus. Des distinctions (average/index, narrow index/broad index, price-weighted/market value-weighted, all share/ composite/ subindex) permettront à l’angliciste de spécialité d’adapter à chaque indice la terminologie française ou anglaise qui lui correspond. Des remarques sur des erreurs courantes, un mini-glossaire, un...

  15. Human tRNALys3UUU Is Pre-Structured by Natural Modifications for Cognate and Wobble Codon Binding through Keto-Enol Tautomerism

    Energy Technology Data Exchange (ETDEWEB)

    Vendeix, Franck A.P.; Murphy, IV, Frank V.; Cantara, William A.; Leszczy,; #324; ska, Gra; #380; yna,; Gustilo, Estella M.; Sproat, Brian; Malkiewicz, Andrzej; Agris, Paul F. [Cornell; (NCSU); (Poland); (Integrated DNA); (SUNYA)

    2013-09-27

    Human tRNALys3UUU (htRNALys3UUU) decodes the lysine codons AAA and AAG during translation and also plays a crucial role as the primer for HIV-1 (human immunodeficiency virus type 1) reverse transcription. The posttranscriptional modifications 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34), 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A37), and pseudouridine (Ψ39) in the tRNA's anticodon domain are critical for ribosomal binding and HIV-1 reverse transcription. To understand the importance of modified nucleoside contributions, we determined the structure and function of this tRNA's anticodon stem and loop (ASL) domain with these modifications at positions 34, 37, and 39, respectively (hASLLys3UUU-mcm5s2U34;ms2t6A3739). Ribosome binding assays in vitro revealed that the hASLLys3UUU-mcm5s2U34;ms2t6A3739 bound AAA and AAG codons, whereas binding of the unmodified ASLLys3UUU was barely detectable. The UV hyperchromicity, the circular dichroism, and the structural analyses indicated that Ψ39 enhanced the thermodynamic stability of the ASL through base stacking while ms2t6A37 restrained the anticodon to adopt an open loop conformation that is required for ribosomal binding. The NMR-restrained molecular-dynamics-derived solution structure revealed that the modifications provided an open, ordered loop for codon binding. The crystal structures of the hASLLys3UUU-mcm5s2U34;ms2t6A3739 bound to the 30S ribosomal subunit with each codon in the A site showed that the

  16. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... the investigations of lighting scenarios carried out in two test installations: White Cube and White Box. The test installations are discussed as large-scale experiential instruments. In these test installations we examine what could potentially occur when light using LED technology is integrated and distributed...

  17. Measuring corruption indicators and indices

    OpenAIRE

    MALITO, Debora Valentina

    2014-01-01

    This Working Paper is a background paper delivered to frame the workshop ‘Global Governance by Indicators: Measuring corruption and corruption indicators’ convened by the Global Governance Programme of the European University Institute in Florence on 17 and 18 October 2013. Successively it was developed further in EUI RSCAS WP 2014/37 - http://hdl.handle.net/1814/30582 The development of more sophisticated corruption measures has been stimulated by consistent and compelling demands for mor...

  18. Benzimidazole -Resistance in Haemonchus Contortus: New PCR-RFLP Method for the Detection of Point Mutation at Codon 167 of Isotype 1 Β-Tubulin Gene

    Directory of Open Access Journals (Sweden)

    A Eslami

    2012-12-01

    Full Text Available Background: Due to the lack of a suitable and economic test for the analysis of the polymorphism at codon 167, we developed a new PCR-RFLP technique, based on a modified forward primer (UT-HC167 MF-primer, to identify simultaneously the SNPs at codons 167 and 200 of isotype 1 β-tubu­lin gene of Haemonchus contortus.Methods: There already are several safe and easy methods for identification of point mutations at codons 198 and 200. Due to the lack of a reliable and easy method for the detection of the single nucleo­tide polymorphism (SNP at codon 167, we developed an innovative PCR-RFLP technique based on a modified forward primer (UT-HC167 MF-primer, in which the nucleotide T at the posi­tion 443 was substituted through a nucleotide A creating a restriction site for restriction endonuc­lease SnaB I in the nucleotide sequences including codon 167. A total of 138 adult male H. contortus were collected from three different geo-climatic areas of Iran. The isolated genomic DNA of each single worm was amplified by PCR using primers flanking codon 167. The PCR product (527 bp was then amplified by semi-nested PCR using the UT-HC167 MF-primer and the reverse primer achiev­ing a PCR product of 451 bp in length. This PCR product was subsequently digested with the restriction endonucleases SnaB I and TaaI for analysis of the mutations at codons 167 and 200, respec­tively.Results: All worms had two alleles encoding for phenylalanine (BZss homozygote for both codons.Conclusion: Using the UT-HC167 MF-primer and a suitable reverse primer designed upstream from codon 200, it is possible to amplify a PCR product which can be used for analysis of the SNPs at all three mentioned codons using RFLP.

  19. Symmetry breaking and adaptation: evidence from a 'toy model' of a virus.

    Science.gov (United States)

    Vargas, J M; Stephens, C R; Waelbroeck, H; Zertuche, F

    1999-07-01

    We argue that an induced breaking of the genetic synonym symmetry due to the action of genetic operators such as mutation can enhance the adaptability of a species to changes in the environment. In the case of a virus, the claim is that the codon bias in the neutralization epitope improves the virus' ability to generate mutants that evade the induced immune response. We support our claim with a simple 'toy model' of a viral epitope evolving in competition with the immune system. The effective selective advantage of a higher mutability leads to a dominance of codons that favor non-synonymous mutations. As further evidence we present a simple model for a genetic regulatory network that leads to adaptive evolution in a population of giraffes by means of an induced symmetry breaking rather than through any direct selective advantage.

  20. ADAPT Dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Diagnostics and Prognostics Testbed (ADAPT) Project Lead: Scott Poll Subject Fault diagnosis in electrical power systems Description The Advanced...

  1. Association between p53 codon 72 polymorphism and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Mohammad Nabavi

    2014-06-01

    Full Text Available Aim : Systemic lupus erythematosus (SLE is a systemic vasculitic disorder, with multiple genes involved in the disease pathogenesis. The p53 gene plays an important role in controlling the cell cycle. We aimed to study the prevalence of p53 polymorphism in SLE patients and analyze the relationship between the p53 polymorphism and clinical-laboratory features of the disease. Material and methods : This case-control study was conducted on patients with confirmed SLE at Namazi Hospital, Shiraz, Iran. Seventy-seven patients with SLE including 9 (11.8% men and 68 (88.2% women with mean age of 25.61 ±10.69 years and 80 healthy controls with mean age of 51.82 ±14.25 years were included. The patients’ information, including the epidemiological profile, disease history, disease symptoms and also the laboratory findings, were extracted from the hospital records. The p53 expression was determined in lyzed lymphocytes. The data were analyzed using SPSS software version 14.00 for Windows considering p < 0.05 as statistically significant. Results : The frequencies of Arg/Arg, Pro/Pro and Arg/Pro among normal controls were 38.8%, 28.8% and 37.5%, respectively, but in the patients, Arg/Arg, Pro/Pro and Arg/Pro genotypes frequencies were shown to be 29.2%, 12.3% and 58.5%, respectively. Thus, heterozygous form of this polymorphism was shown to be associated with the disease more than the homozygous alleles. There was a significant relationship between the different allele types of p53 and some clinical features of SLE. There was no association between the different allele types and any of the initial manifestations of the disease and the laboratory findings, as well. Conclusions: In an Iranian population the functional oncoprotein of p53 with codon 72 polymorphism may play an important role in the pathogenesis and clinical presentation of SLE.

  2. Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Sigal, R.J.; Doria, A.; Warram, J.H.; Krolewski, A.S. [Joslin Diabetes Center, Boston, MA (United States)

    1996-04-01

    Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM). Modest associations between NIDDM and a GGG-AGG single base substitution (corresponding to a glycine-arginine amino acid substitution) in codon 972 of the gene have been found, but none reached statistical significance. To examine further how large a proportion of NIDDM cases could be caused by the mutation, we performed a stratified analysis combining the results from the 6 earlier studies and those from our panel of 192 unrelated NIDDM subjects and 104 healthy controls. In addition, we looked for a possibility that the codon 972 mutation plays a role only in the presence of certain conditions. Genomic DNA samples obtained from NIDDM cases and healthy controls were genotyped using a PCR-restriction fragment length polymorphism protocol modified for genomic DNA. The GGG{r_arrow}AGG substitution was found in 5.7% of the diabetic subjects (11 of 192) and 6.9% of the controls (7 of 104). The difference between groups was not statistically significant, and it was not different from the results of other studies. The Mantel-Haenszel summary odds ratio across all studies was 1.49 (P < 0.05; 95% confidence intervals, 1.01-2.2). This summary odds ratio is consistent with a small proportion of NIDDM cases ({approximately}3%) being caused by the mutation. Exploratory subgroup analyses on our panel suggested a clustering of NIDDM, the codon 972 mutation, and overweight, raising the hypothesis that the mutation may predispose to NIDDM only in the presence of excess body weight. 9 refs., 2 tabs.

  3. Protein and DNA sequence determinants of thermophilic adaptation.

    Directory of Open Access Journals (Sweden)

    Konstantin B Zeldovich

    2007-01-01

    Full Text Available There have been considerable attempts in the past to relate phenotypic trait--habitat temperature of organisms--to their genotypes, most importantly compositions of their genomes and proteomes. However, despite accumulation of anecdotal evidence, an exact and conclusive relationship between the former and the latter has been elusive. We present an exhaustive study of the relationship between amino acid composition of proteomes, nucleotide composition of DNA, and optimal growth temperature (OGT of prokaryotes. Based on 204 complete proteomes of archaea and bacteria spanning the temperature range from -10 degrees C to 110 degrees C, we performed an exhaustive enumeration of all possible sets of amino acids and found a set of amino acids whose total fraction in a proteome is correlated, to a remarkable extent, with the OGT. The universal set is Ile, Val, Tyr, Trp, Arg, Glu, Leu (IVYWREL, and the correlation coefficient is as high as 0.93. We also found that the G + C content in 204 complete genomes does not exhibit a significant correlation with OGT (R = -0.10. On the other hand, the fraction of A + G in coding DNA is correlated with temperature, to a considerable extent, due to codon patterns of IVYWREL amino acids. Further, we found strong and independent correlation between OGT and the frequency with which pairs of A and G nucleotides appear as nearest neighbors in genome sequences. This adaptation is achieved via codon bias. These findings present a direct link between principles of proteins structure and stability and evolutionary mechanisms of thermophylic adaptation. On the nucleotide level, the analysis provides an example of how nature utilizes codon bias for evolutionary adaptation to extreme conditions. Together these results provide a complete picture of how compositions of proteomes and genomes in prokaryotes adjust to the extreme conditions of the environment.

  4. SCREENING FOR GENETIC CHANGES AND CODON 129 POLYMORPHISM IN PRNP GENE IN HEALTHY SLOVENIAN POPULATION AND SPORADIC CASES OF CREUTZFELDT-JAKOB DISEASE

    Directory of Open Access Journals (Sweden)

    Sava Smerkolj

    2004-11-01

    Full Text Available Background. Prion protein has an important role in development of prion diseases, fatal neurodegenerative disorders. As the codon 129 genotype of the prion protein gene (PRNP is a known susceptibility factor for the diseases, we wanted to determine its distribution in healthy Slovenian population and also in cases of sporadic Creutzfeldt-Jakob disease (sCJD. Furthermore, we wanted to screen the whole gene in order to establish the presence of genetic changes.Methods. We screened 350 DNA samples of healthy blood donors and 12 DNA samples of patients deceased of sCJD. After the amplification and conformation analysis had been done, the gene was sequenced using an automatic sequencer.Results. Methionine homozygotes comprised 46.8% of healthy population, valine homozygotes 12.1% and heterozygotes 41.1%; out of 12 sCJD patients 10 were methionine homozygotes (83.3%, 1 was valine homozygote (8.3% and 1 was heterozygote (8.3%.Found SNPs were combination of codon 76 change (228C > T and codon 84 change (252T > C in a single sample of healthy population, combination of codon 68 change (204T > C and codon 76 change (228C > T in two samples of healthy population and codon 117 change (351A > G in a healthy population sample and in a valine homozygote patient.Conclusions. In comparison to the pooled Caucasian population is genotype M/M frequency slightly increased on account of decreased genotype M/V frequency in healthy Slovenian population, suggesting a little higher risk for acquiring a new variant of CJD (vCJD, because up to date all confirmed vCJD cases except one heterozygote were methionine homozygotes. Codon 129 genotype distribution in sCJD can be described as disease-specific. The absence of pathogenic mutations in sCJD patients confirms the non-familial, sporadic disease form.

  5. Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

    Directory of Open Access Journals (Sweden)

    Caroline Pinto de Andrade

    2011-10-01

    Full Text Available Scrapie is a transmissible spongiform encephalopathy of sheeps and goats, associated with the deposition of a isoform of the prion protein (PrPsc. This isoform presents an altered conformation that leads to aggregation in the host's central nervous and lymphoreticular systems. Predisposition to the prion agent infection can be influenced by specific genotypes related to mutations in amino acids of the PrPsc gene. The most characterized mutations occur at codons 136, 154 and 171, with genotypes VRQ being the most susceptible and ARR the most resistant. In this study we have analyzed polymorphisms in 15 different codons of the PrPsc gene in sheeps from a Suffolk herd from Brazil affected by an outbreak of classical scrapie. Amplicons from the PrPsc gene, encompassing the most relevant altered codons in the protein, were sequenced in order to determine each animal's genotype. We have found polymorphisms at 3 of the 15 analyzed codons (136, 143 and 171. The most variable codon was 171, where all described alleles were identified. A rare polymorphism was found at the 143 codon in 4% of the samples analyzed, which has been described as increasing scrapie resistance in otherwise susceptible animals. No other polymorphisms were detected in the remaining 12 analyzed codons, all of them corresponding to the wild-type prion protein. Regarding the risk degree of developing scrapie, most of the animals (96% had genotypes corresponding to risk groups 1 to 3 (very low to moderate, with only 4% in the higher risks group. Our data is discussed in relation to preventive measures involving genotyping and positive selection to control the disease.

  6. The predominance of codon 39 (c>t mutation of HBB gene in a portion of the Algerian population (Northeast Algeria

    Directory of Open Access Journals (Sweden)

    Belhadi Kamilia

    2017-04-01

    Full Text Available This study was planned to determine the frequency of β-thalassemia mutations in Batna region (Northeast Algeria. Nineteen blood samples of clinically thalassemic children patients were collected from Department of Pediatrics, University Hospital of Batna. We carried out the molecular genetics of beta globin gene by the method of minisequencing using Snapshot™ kit (Applied Biosystems in search of the four most common HBB genetic variants including three β-thalassemia mutations: codon 39(C>T (HBB: c.118C>T, IVSI-110(G>A (HBB: c.93-21G>A, and IVSI-1-2(T>G (HBB: c.92+2T>G, as well as the hemoglobin S variant (HBB: c.20A>T. We used direct DNA sequencing to detect the rare mutations of beta-globin gene. We have revealed the presence of four different β-globin gene mutations responsible for β-thalassemia in Batna region. According to our results, the nonsense mutation at codon 39 (C>T is the most frequent mutation type in our province, the same as other geographical regions of Algeria. It is followed by codon 54(-T, detected in a second Algerian family (the proband was homozygote, and the first association of Hb Knossos: codon 27 (G>T allele with codon 39 (C>T in the Algerian population. Here we reportws also the association of codon 39(C>T with IVS-I-110 (G>A. Our preliminary results show the predominance of codon 39 (c>t mutation of HBB gene in Batna region.

  7. Adaptation Stories

    International Development Research Centre (IDRC) Digital Library (Canada)

    By Reg'

    formed a real foundation for endogenous, and, therefore, sustainable, strategies for adaptation to climate change. The stories reinforce what we already knew: that successful adaptation must come from the people who are living on the front lines, facing the many problems caused by climate change and climate variation.

  8. Comparative analysis of KRAS codon 12, 13, 18, 61, and 117 mutations using human MCF10A isogenic cell lines.

    Science.gov (United States)

    Stolze, Britta; Reinhart, Stefanie; Bulllinger, Lars; Fröhling, Stefan; Scholl, Claudia

    2015-02-23

    KRAS mutations occur in one third of human cancers and cluster in several hotspots, with codons 12 and 13 being most commonly affected. It has been suggested that the position and type of amino acid exchange influence the transforming capacity of mutant KRAS proteins. We used MCF10A human mammary epithelial cells to establish isogenic cell lines that express different cancer-associated KRAS mutations (G12C, G12D, G12V, G13C, G13D, A18D, Q61H, K117N) at physiological or elevated levels, and investigated the biochemical and functional consequences of the different variants. The overall effects of low-expressing mutants were moderate compared to overexpressed variants, but allowed delineation of biological functions that were related to specific alleles rather than KRAS expression level. None of the mutations induced morphological changes, migratory abilities, or increased phosphorylation of ERK, PDK1, and AKT. KRAS-G12D, G12V, G13D, and K117N mediated EGF-independent proliferation, whereas anchorage-independent growth was primarily induced by K117N and Q61H. Both codon 13 mutations were associated with increased EGFR expression. Finally, global gene expression analysis of MCF10A-G13D versus MCF10A-G12D revealed distinct transcriptional changes. Together, we describe a useful resource for investigating the function of multiple KRAS mutations and provide insights into the differential effects of these variants in MCF10A cells.

  9. Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons

    DEFF Research Database (Denmark)

    Macvanin, Mirjana; Gonzalez de Valdivia, Ernesto I; Ardell, David H

    2007-01-01

    Expression of minigenes encoding tetra- or pentapeptides MXLX or MXLXV (E peptides), where X is a nonpolar amino acid, renders cells erythromycin resistant whereas expression of minigenes encoding tripeptide MXL does not. By using a 3A' reporter gene system beginning with an E-peptide-encoding se......Expression of minigenes encoding tetra- or pentapeptides MXLX or MXLXV (E peptides), where X is a nonpolar amino acid, renders cells erythromycin resistant whereas expression of minigenes encoding tripeptide MXL does not. By using a 3A' reporter gene system beginning with an E......, is associated with an erythromycin resistance phenotype upon gene induction. Our results suggest that, while a stop codon at +4 gives a tripeptide product (MIL) and erythromycin sensitivity, UGG or GGG codons at the same position give a tetrapeptide product (MILW or MILG) and phenotype of erythromycin...... with erythromycin resistance. Several genes in Escherichia coli fulfill the requirements of high mRNA expression and an E-peptide sequence followed by UGG or GGG at position +4 or +5 and should potentially be able to give an erythromycin resistance phenotype....

  10. A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria

    Directory of Open Access Journals (Sweden)

    Farias Fabiana HG

    2012-07-01

    Full Text Available Abstract Background L-2-hydroxyglutaric aciduria is a metabolic repair deficiency characterized by elevated levels of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid. Neurological signs associated with the disease in humans and dogs include seizures, ataxia and dementia. Case presentation Here we describe an 8 month old Yorkshire terrier that presented with episodes of hyperactivity and aggressive behavior. Between episodes, the dog’s behavior and neurologic examinations were normal. A T2 weighted MRI of the brain showed diffuse grey matter hyperintensity and a urine metabolite screen showed elevated 2-hydroxyglutaric acid. We sequenced all 10 exons and intron-exon borders of L2HGDH from the affected dog and identified a homozygous A to G transition in the initiator methionine codon. The first inframe methionine is at p.M183 which is past the mitochondrial targeting domain of the protein. Initiation of translation at p.M183 would encode an N-terminal truncated protein unlikely to be functional. Conclusions We have identified a mutation in the initiation codon of L2HGDH that is likely to result in a non-functional gene. The Yorkshire terrier could serve as an animal model to understand the pathogenesis of L-2-hydroxyglutaric aciduria and to evaluate potential therapies.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma.

    Science.gov (United States)

    Prevost, Luanna B; Smith, Michelle K; Knight, Jennifer K

    2016-01-01

    Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon mutation potentially impacts replication, transcription, and translation. We then used computer-assisted lexical analysis combined with human scoring to categorize student responses. The lexical analysis models showed high agreement with human scoring, demonstrating that this approach can be successfully used to analyze large numbers of student written responses. The results of this analysis show that students' ideas about one process in the central dogma can affect their thinking about subsequent and previous processes, leading to mixed models of conceptual understanding. © 2016 L. B. Prevost et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  13. Codon Optimization Significantly Improves the Expression Level of α-Amylase Gene from Bacillus licheniformis in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Jian-Rong Wang

    2015-01-01

    Full Text Available α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinant α-amylase from Bacillus licheniformis (B. licheniformis, the α-amylase gene from B. licheniformis was optimized according to the codon usage of Pichia pastoris (P. pastoris and expressed in P. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level in P. pastoris after methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate for α-amylase production in industrial use.

  14. Distribution of the ribosome associated endonuclease Rae1 and the potential role of conserved amino acids in codon recognition.

    Science.gov (United States)

    Condon, Ciarán; Piton, Jéremie; Braun, Frédérique

    2018-03-20

    We recently identified a novel ribonuclease in Bacillus subtilis called Rae1 that cleaves mRNAs in a translation-dependent manner. Rae1 is a member of the NYN/PIN family of ribonucleases and is highly conserved in the Firmicutes, the Cyanobacteria and the chloroplasts of photosynthetic algae and plants. We have proposed a model in which Rae1 enters the A-site of ribosomes that are paused following translation of certain sequences that are still ill-defined. In the only case identified thus far, Rae1 cleaves between a conserved glutamate and lysine codon during translation of a short peptide called S1025. Certain other codons are also tolerated on either side of the cleavage site, but these are recognized less efficiently. The model of Rae1 docked in the A-site allows us to make predictions about which conserved residues may be important for recognition of mRNA, the tRNA in the adjacent P-site and binding to the 50S ribosome subunit.

  15. Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population.

    Science.gov (United States)

    Rivu, Sanzana Fareen; Apu, Mohd Nazmul Hasan; Shabnaz, Samia; Nahid, Noor Ahmed; Islam, Md Reazul; Al-Mamun, Mir Md Abdullah; Nahar, Zabun; Rabbi, Sikder Nahidul Islam; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Hasnat, Abul

    2017-08-01

    Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160Ccolorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR=2.58, 95% CI=1.77-3.77, pcolorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (pcolorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR=2.02, 95% CI=1.42-2.87, pcolorectal cancer development in Bangladeshi population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Toothbrush Adaptations.

    Science.gov (United States)

    Exceptional Parent, 1987

    1987-01-01

    Suggestions are presented for helping disabled individuals learn to use or adapt toothbrushes for proper dental care. A directory lists dental health instructional materials available from various organizations. (CB)

  17. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    2017-01-01

    intense relational mechanisms provide an effective means for contingency adaptation and therefore reduce the probability of premature termination. However, in situations where relationships are already governed by longer duration contracts, we argue that investments in relational mechanism create...

  18. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    We investigate why some exchange relationships terminate prematurely. We argue that investments in informal governance structures induce premature termination in relationships already governed by formal contracts. The formalized adaptive behavior of formal governance structures and the flexible...... and reciprocal adaptation of informal governance structure create ambiguity in situations of contingencies, which, subsequently, increases the likelihood of premature relationship termination. Using a large sample of exchange relationships in the global service provider industry, we find support for a hypothesis...

  19. Strategic Adaptation

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    This article provides an overview of theoretical contributions that have influenced the discourse around strategic adaptation including contingency perspectives, strategic fit reasoning, decision structure, information processing, corporate entrepreneurship, and strategy process. The related...... concepts of strategic renewal, dynamic managerial capabilities, dynamic capabilities, and strategic response capabilities are discussed and contextualized against strategic responsiveness. The insights derived from this article are used to outline the contours of a dynamic process of strategic adaptation...

  20. Adaptive ethnography

    DEFF Research Database (Denmark)

    Berth, Mette

    2005-01-01

    This paper focuses on the use of an adaptive ethnography when studying such phenomena as young people's use of mobile media in a learning perspective. Mobile media such as PDAs and mobile phones have a number of affordances which make them potential tools for learning. However, before we begin...... formal and informal learning contexts. The paper also proposes several adaptive methodological techniques for studying young people's interaction with mobiles....

  1. Adaptive evolution of the matrix extracellular phosphoglycoprotein in mammals

    Directory of Open Access Journals (Sweden)

    Machado João

    2011-11-01

    Full Text Available Abstract Background Matrix extracellular phosphoglycoprotein (MEPE belongs to a family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs that play a key role in skeleton development, particularly in mineralization, phosphate regulation and osteogenesis. MEPE associated disorders cause various physiological effects, such as loss of bone mass, tumors and disruption of renal function (hypophosphatemia. The study of this developmental gene from an evolutionary perspective could provide valuable insights on the adaptive diversification of morphological phenotypes in vertebrates. Results Here we studied the adaptive evolution of the MEPE gene in 26 Eutherian mammals and three birds. The comparative genomic analyses revealed a high degree of evolutionary conservation of some coding and non-coding regions of the MEPE gene across mammals indicating a possible regulatory or functional role likely related with mineralization and/or phosphate regulation. However, the majority of the coding region had a fast evolutionary rate, particularly within the largest exon (1467 bp. Rodentia and Scandentia had distinct substitution rates with an increased accumulation of both synonymous and non-synonymous mutations compared with other mammalian lineages. Characteristics of the gene (e.g. biochemical, evolutionary rate, and intronic conservation differed greatly among lineages of the eight mammalian orders. We identified 20 sites with significant positive selection signatures (codon and protein level outside the main regulatory motifs (dentonin and ASARM suggestive of an adaptive role. Conversely, we find three sites under selection in the signal peptide and one in the ASARM motif that were supported by at least one selection model. The MEPE protein tends to accumulate amino acids promoting disorder and potential phosphorylation targets. Conclusion MEPE shows a high number of selection signatures, revealing the crucial role of positive selection in the

  2. Is adaptation. Truly an adaptation? Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2008-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning. The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition

  3. Strategic Adaptation

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    concepts of strategic renewal, dynamic managerial capabilities, dynamic capabilities, and strategic response capabilities are discussed and contextualized against strategic responsiveness. The insights derived from this article are used to outline the contours of a dynamic process of strategic adaptation......This article provides an overview of theoretical contributions that have influenced the discourse around strategic adaptation including contingency perspectives, strategic fit reasoning, decision structure, information processing, corporate entrepreneurship, and strategy process. The related....... This model incorporates elements of central strategizing, autonomous entrepreneurial behavior, interactive information processing, and open communication systems that enhance the organization's ability to observe exogenous changes and respond effectively to them....

  4. Adaptive test

    DEFF Research Database (Denmark)

    Kjeldsen, Lars Peter; Eriksen, Mette Rose

    2010-01-01

    Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale.......Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale....

  5. [The adaptation to contact lenses].

    Science.gov (United States)

    Koos, D; Koos, M J

    1992-01-01

    The indications of contact lens adaptation in optical purpose are widely large, starting, with refractive errors [correction of vices], unilateral and bilateral aphakia, myopia, anisometropia and astigmatism, together with the use of contact lens in esthetic purpose. We have been presented the adaptation techniques, the supervise, and maintenance of contact lens.

  6. Tracking adaptation and measuring development

    Energy Technology Data Exchange (ETDEWEB)

    Brooks, Nick; Anderson, Simon; Ayers, Jessica; Burton, Ian; Tellam, Ian

    2011-11-15

    This is the first paper in the new IIED Climate Change Working Paper series. As adaptation to climate change becomes the focus of increasing attention and the target of significant spending, there is a growing need for frameworks and tools that enable organisations to track and assess the outcomes of adaptation interventions. This paper presents a coherent framework for climate change adaptation programming, including potential indicators, or indicator categories/types, for tracking and evaluating the success of adaptation support and adaptation interventions. The paper begins with a discussion of some of the key issues related to the evaluation of adaptation, and outlines some of the main difficulties and constraints with respect to the development of adaptation indicators. Next, an evaluation framework is proposed and indicator categories or 'domains' are identified. Lastly, key conclusions are provided and a theory of change is outlined that shows how development and use of the framework could lead to more effective adaptation investments for climate resilient development.

  7. The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, S.J.; Gladwin, A.J.; Dixon, M.J. [Univ. of Manchester (United Kingdom)

    1997-03-01

    Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified. In the current investigation, 25 previously undescribed mutations, which are spread throughout the gene, are presented. This brings the total reported to date to 35, which represents a detection rate of 60%. Of the mutations that have been reported to date, all but one result in the introduction of a premature-termination codon into the predicted protein, treacle. Moreover, the mutations are largely family specific, although a common 5-bp deletion in exon 24 (seven different families) and a recurrent splicing mutation in intron 3 (two different families) have been identified. This mutational spectrum supports the hypothesis that TCS results from haploin-sufficiency. 49 refs., 4 figs., 3 tabs.

  8. Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2006-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning.

  9. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  10. An AUG codon conserved for protein function rather than translational initiation: the story of the protein sElk1.

    Directory of Open Access Journals (Sweden)

    Noemie Legrand

    Full Text Available Elk1 belongs to the ternary complex (TCF subfamily of the ETS-domain transcription factors. Several studies have implicated an important function for Elk1 in the CNS including synaptic plasticity and cell differentiation. Whilst studying ELK1 gene expression in rat brain a 54 aa N-terminally truncated isoform lacking the DBD was observed on immunoblots. A similar protein was also detected in NGF differentiated PC12 cells. It was proposed that this protein, referred to as sElk1, arose due to a de-novo initiation event at the second AUG codon on the Elk1 ORF. Transient over-expression of sElk1 potentiated neurite growth in the PC12 model and induced differentiation in the absence of NGF, leading to the proposition that it may have a specific function in the CNS. Here we report on the translational expression from the mouse and rat transcript and compare it with our earlier published work on human. Results demonstrate that the previously observed sElk1 protein is a non-specific band arising from the antibody employed. The tight conservation of the internal AUG reported to drive sElk1 expression is in fact coupled to Elk1 protein function, a result consistent with the Elk1-SRE crystal structure. It is also supported by the observed conservation of this methionine in the DBD of all ETS transcription factors independent of the N- or C-terminal positioning of this domain. Reporter assays demonstrate that elements both within the 5'UTR and downstream of the AUGElk1 serve to limit 40S access to the AUGsElk1 codon.

  11. Adaptation is...

    International Development Research Centre (IDRC) Digital Library (Canada)

    IDRC

    vital sector is under threat. While it is far from the only development challenge facing local farmers, extreme variations in the climate of West Africa in the past several decades have dealt the region a bad hand. Drought and flood now follow each other in succession. Adaptation is... “The floods spoiled our harvests and we.

  12. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    and reciprocal adaptation of informal governance structure create ambiguity in situations of contingencies, which, subsequently, increases the likelihood of premature relationship termination. Using a large sample of exchange relationships in the global service provider industry, we find support for a hypothesis...

  13. Adaptation Insights

    International Development Research Centre (IDRC) Digital Library (Canada)

    be given greater access to relevant information to help them adapt their farming practices and socio- economic strategies to climate change? To address this challenge, the project “InfoClim,” led by Senegal's. Ecological Monitoring Centre. (CSE) with support from the. CCAA program, aims at improving the access of farmers ...

  14. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Kongshaug, Jesper; Søndergaard, Karin

    2015-01-01

    differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...

  15. Codon-defined ribosomal pausing in Escherichia coli detected by using the pyrE attenuator to probe the coupling between transcription and translation

    DEFF Research Database (Denmark)

    Bonekamp, Fons; Andersen, Henrik Dalbøge; Christensen, Torkild

    1985-01-01

    to be tested were placed in the middle of the leader peptide and the downstream transcription of a pyrE"lacZ gene was monitored by measuring beta-galactosidase activity. The substitution, one by one, of three AGG codons for arginine with three CGT codons for the same amino acid residue was found to cause a two...

  16. mRNA secondary structure at start AUG codon is a key limiting factor for human protein expression in Escherichia coli

    International Nuclear Information System (INIS)

    Zhang Weici; Xiao Weihua; Wei Haiming; Zhang Jian; Tian Zhigang

    2006-01-01

    Codon usage and thermodynamic optimization of the 5'-end of mRNA have been applied to improve the efficiency of human protein production in Escherichia coli. However, high level expression of human protein in E. coli is still a challenge that virtually depends upon each individual target genes. Using human interleukin 10 (huIL-10) and interferon α (huIFN-α) coding sequences, we systematically analyzed the influence of several major factors on expression of human protein in E. coli. The results from huIL-10 and reinforced by huIFN-α showed that exposing AUG initiator codon from base-paired structure within mRNA itself significantly improved the translation of target protein, which resulted in a 10-fold higher protein expression than the wild-type genes. It was also noted that translation process was not affected by the retained short-range stem-loop structure at Shine-Dalgarno (SD) sequences. On the other hand, codon-optimized constructs of huIL-10 showed unimproved levels of protein expression, on the contrary, led to a remarkable RNA degradation. Our study demonstrates that exposure of AUG initiator codon from long-range intra-strand secondary structure at 5'-end of mRNA may be used as a general strategy for human protein production in E. coli

  17. Alignment-based and alignment-free methods converge with experimental data on amino acids coded by stop codons at split between nuclear and mitochondrial genetic codes.

    Science.gov (United States)

    Seligmann, Hervé

    2018-04-03

    Genetic codes mainly evolve by reassigning punctuation codons, starts and stops. Previous analyses assuming that undefined amino acids translate stops showed greater divergence between nuclear and mitochondrial genetic codes. Here, three independent methods converge on which amino acids translated stops at split between nuclear and mitochondrial genetic codes: (a) alignment-free genetic code comparisons inserting different amino acids at stops; (b) alignment-based blast analyses of hypothetical peptides translated from non-coding mitochondrial sequences, inserting different amino acids at stops; (c) biases in amino acid insertions at stops in proteomic data. Hence short-term protein evolution models reconstruct long-term genetic code evolution. Mitochondria reassign stops to amino acids otherwise inserted at stops by codon-anticodon mismatches (near-cognate tRNAs). Hence dual function (translation termination and translation by codon-anticodon mismatch) precedes mitochondrial reassignments of stops to amino acids. Stop ambiguity increases coded information, compensates endocellular mitogenome reduction. Mitochondrial codon reassignments might prevent viral infections. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Over Expression of a tRNALeu Isoacceptor Changes Charging Pattern of Leucine tRNAs and Reveals New Codon Reading

    DEFF Research Database (Denmark)

    Sørensen, Michael Askvad; Elf, J.; Bouakaz, E.

    2005-01-01

    During mRNA translation, synonymous codons for one amino acid are often read by different isoaccepting tRNAs. The theory of selective tRNA charging predicts greatly varying percentages of aminoacylation among isoacceptors in cells starved for their common amino acid. It also predicts major change...

  19. Translational Control of the SigR-Directed Oxidative Stress Response in Streptomyces via IF3-Mediated Repression of a Noncanonical GTC Start Codon.

    Science.gov (United States)

    Feeney, Morgan A; Chandra, Govind; Findlay, Kim C; Paget, Mark S B; Buttner, Mark J

    2017-06-13

    The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry. IMPORTANCE In all sigma factor-antisigma factor regulatory switches, the relative abundance of the two proteins is critical to the proper functioning of the system. Many sigma-antisigma operons are cotranscribed and translationally coupled, leading to a generic assumption that the sigma and antisigma factors are produced in a fixed 1:1 ratio. In the case of sigR - rsrA , we show instead that the antisigma factor is produced in excess over the sigma factor, providing a buffer to prevent spurious release of sigma activity. This excess arises in part because sigR has an extremely rare noncanonical GTC start codon, and as a result, SigR translation initiation is repressed by IF3. This finding highlights the potential significance

  20. Adaptive Playware in Physical Games

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Thorsteinsson, Arnar Tumi

    2011-01-01

    We describe how playware and games may adapt to the interaction of the individual user. We hypothesize that in physical games there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user’s capabilities, so...... that the activity automatically will match the capability of the individual user. With small test groups, we investigate how different age groups and gender groups physically interact with some playware games, and find indications of differences between the groups. Despite the small test set, the results...... are a proof of existence of differences and of the need for adaptation, and therefore we investigate adaptation as an important issue for playware. With simple playware games, we show that the adaptation will speed the physical game up and down to find the appropriate level that matches the reaction speed...

  1. Adaptation Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Huq, Saleemul

    2011-11-15

    Efforts to help the world's poor will face crises in coming decades as climate change radically alters conditions. Action Research for Community Adapation in Bangladesh (ARCAB) is an action-research programme on responding to climate change impacts through community-based adaptation. Set in Bangladesh at 20 sites that are vulnerable to floods, droughts, cyclones and sea level rise, ARCAB will follow impacts and adaptation as they evolve over half a century or more. National and international 'research partners', collaborating with ten NGO 'action partners' with global reach, seek knowledge and solutions applicable worldwide. After a year setting up ARCAB, we share lessons on the programme's design and move into our first research cycle.

  2. Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression

    International Nuclear Information System (INIS)

    Nguyen, Kim-Lien; Llano, Manuel; Akari, Hirofumi; Miyagi, Eri; Poeschla, Eric M.; Strebel, Klaus; Bour, Stephan

    2004-01-01

    Two HIV-1 accessory proteins, Vpu and Vif, are notoriously difficult to express autonomously in the absence of the viral Tat and Rev proteins. We examined whether the codon bias observed in the vpu and vif genes relative to highly expressed human genes contributes to the Rev dependence and low expression level outside the context of the viral genome. The entire vpu gene as well as the 5' half of the vif gene were codon optimized and the resulting open reading frames (ORFs) (vphu and hvif, respectively) were cloned in autonomous expression vectors under the transcriptional control of the CMV promoter. Codon optimization efficiently removed the expression block observed in the native genes and allowed high levels of Rev- and Tat-independent expression of Vpu and Vif. Most of the higher protein levels detected are accounted for by enhanced steady-state levels of the mRNA encoding the optimized species. Nuclear run-on experiments show for the first time that codon optimization has no effect on the rate of transcriptional initiation or elongation of the vphu mRNA. Instead, optimization of the vpu gene was found to stabilize the vphu mRNA in the nucleus and enhance its export to the cytoplasm. This was achieved by allowing the optimized mRNA to use a new CRM1-independent nuclear export pathway. This work provides a better understanding of the molecular mechanisms underlying the process of codon optimization and introduces novel tools to study the biological functions of the Vpu and Vif proteins independently of other viral proteins

  3. Solar tomography adaptive optics.

    Science.gov (United States)

    Ren, Deqing; Zhu, Yongtian; Zhang, Xi; Dou, Jiangpei; Zhao, Gang

    2014-03-10

    Conventional solar adaptive optics uses one deformable mirror (DM) and one guide star for wave-front sensing, which seriously limits high-resolution imaging over a large field of view (FOV). Recent progress toward multiconjugate adaptive optics indicates that atmosphere turbulence induced wave-front distortion at different altitudes can be reconstructed by using multiple guide stars. To maximize the performance over a large FOV, we propose a solar tomography adaptive optics (TAO) system that uses tomographic wave-front information and uses one DM. We show that by fully taking advantage of the knowledge of three-dimensional wave-front distribution, a classical solar adaptive optics with one DM can provide an extra performance gain for high-resolution imaging over a large FOV in the near infrared. The TAO will allow existing one-deformable-mirror solar adaptive optics to deliver better performance over a large FOV for high-resolution magnetic field investigation, where solar activities occur in a two-dimensional field up to 60'', and where the near infrared is superior to the visible in terms of magnetic field sensitivity.

  4. Adaptive sampler

    Science.gov (United States)

    Watson, B.L.; Aeby, I.

    1980-08-26

    An adaptive data compression device for compressing data is described. The device has a frequency content, including a plurality of digital filters for analyzing the content of the data over a plurality of frequency regions, a memory, and a control logic circuit for generating a variable rate memory clock corresponding to the analyzed frequency content of the data in the frequency region and for clocking the data into the memory in response to the variable rate memory clock.

  5. Adaptive positioner

    International Nuclear Information System (INIS)

    Labrador Pavon, I.

    1993-01-01

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 6 refs

  6. Adaptable positioner

    International Nuclear Information System (INIS)

    Labrador Pavon, I.

    1993-01-01

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 22 fig. 6 ref

  7. ADAPTATION EVALUATION

    Directory of Open Access Journals (Sweden)

    Björn PETERS, M.Sc.

    2001-01-01

    Full Text Available Twenty subjects with lower limb disabilities participated in a simulator study. The purpose of the study was to investigate how an Adaptive Cruise Control (ACC system together with two different hand controls for accelerator and brake influenced workload, comfort and driving behaviour and to further develop a method to evaluate vehicle adaptations for drivers with disabilities. The installed ACC system could maintain a constant speed selected and set by the driver and it also adapted speed in order to keep a safe distance to a leading vehicle. Furthermore, it included a stop-and-go function. Two common types of hand controls for accelerator and brake were used. The hand controls were different both with respect to function, single or dual levers, and position, on the steering column or between the front seats. The subjects were all experienced drivers of adapted cars equipped with hand controls. All subjects drove 100km at two occasions, with and without the ACC system available but with the same hand control. Subjective workload was found to be significantly lower and performance better for the ACC condition. The difference in speed variation between manual and ACC supported driving increased with the distance driven which seems to support the previous finding. The subjects thought they could control both speed and distance to leading vehicles better while the ACC was available. ACC driving did not influence reaction time, speed level, lateral position or variation in lateral position. Headway during car following situations was shorter for the ACC condition compared to manual driving. The ACC was well received, trusted and wanted. It was concluded that the ACC system substantially decreased workload, increased comfort and did not influence safety negatively. The only difference found between the two types of hand controls was that drivers using the dual lever system had less variation in lateral position. The applied evaluation method proved

  8. Tamper indicating packaging

    International Nuclear Information System (INIS)

    Baumann, M.J.; Bartberger, J.C.; Welch, T.D.

    1994-01-01

    Protecting sensitive items from undetected tampering in an unattended environment is crucial to the success of non-proliferation efforts relying on the verification of critical activities. Tamper Indicating Packaging (TIP) technologies are applied to containers, packages, and equipment that require an indication of a tamper attempt. Examples include: the transportation and storage of nuclear material, the operation and shipment of surveillance equipment and monitoring sensors, and the retail storage of medicine and food products. The spectrum of adversarial tampering ranges from attempted concealment of a pin-hole sized penetration to the complete container replacement, which would involve counterfeiting efforts of various degrees. Sandia National Laboratories (SNL) has developed a technology base for advanced TIP materials, sensors, designs, and processes which can be adapted to various future monitoring systems. The purpose of this technology base is to investigate potential new technologies, and to perform basic research of advanced technologies. This paper will describe the theory of TIP technologies and recent investigations of TIP technologies at SNL

  9. Methacholine PC20 In African Americans And Whites With Asthma With Homozygous Genotypes at ADRB2 Codon 16

    Science.gov (United States)

    Blake, Kathryn; Cury, James D.; Hossain, Jobayer; Tantisira, Kelan; Wang, Jianwei; Mougey, Edward; Lima, John

    2013-01-01

    BACKGROUND African Americans have worse asthma outcomes compared to whites. Adrenoceptor beta 2, surface gene (ADRB2) Gly16Arg genotypes have been associated with β2-agonist bronchodilator response, asthma exacerbation rate, response to methacholine, and lung function decline but not specifically in African Americans. OBJECTIVE We sought to compare the provocative concentration of methacholine that causes a 20% fall in FEV1 (PC20) in African Americans and whites with asthma who were ADRB2 homozygous at codon16 (Arg16Arg or Gly16Gly). METHODS African Americans and whites whose parents and grandparents were of the same race, aged ≥ 10 years, with baseline FEV1 of ≥60% predicted, and no upper or lower respiratory tract infection within the previous 2 weeks meeting genotype criteria were enrolled. PC20 was measured after withholding short-acting and long-acting β2-agonists for 8 and 12 hours respectively, montelukast for 24 hours, ipratropium bromide and inhaled corticosteroids for 12 hours, and antihistamines for 72 hours. RESULTS 423 participants were screened and 88 had a positive challenge. Participants were 32yrs ± 19yrs (mean ± SD), 70% female, 51% White (vs. African American), 6% Hispanic. Similar numbers of participants were using inhaled corticosteroids by race and genotype. There were significant differences in log PC20 between race/genotype groups (p=0.012). African American Arg16Arg participants had a lower log PC20 than White Gly16Gly (p=0.009) and African American Gly16Gly (p=0.041) participants. Both race and genotype contributed significantly to the model (p=0.037 and p=0.014, respectively) but there was no interaction between race and genotype on log PC20. CONCLUSIONS AND CLINICAL RELEVANCE Airway hyperresponsiveness is influenced by race and the ADRB2 codon 16 polymorphism. African Americans with the Arg16Arg genotype have increased airway reactivity and may be at risk for worse asthma outcomes. Inclusion of genetic information as an

  10. HIV-1 replication in CD4+ T cell lines: the effects of adaptation on co-receptor use, tropism, and accessory gene function.

    Science.gov (United States)

    Dejucq, N

    2000-09-01

    We studied the replication of HIV-1 macrophage-tropic CCR5-using strains (R5) in CD4+ T cell lines to better understand the switch in co-receptor use of such strains during disease progression and to assess resulting changes in cell tropism. We found that the majority of R5 strains cannot replicate in CD4+ T cell lines without adaptation by serial passage. A small minority of primary R5 isolates, however, were able to infect two T cell lines, Molt4 and SupT1. This expanded tropism was due to the use of undetectable levels of CCR5 rather than CXCR4 or alternative receptors. In contrast, HIV-1sF162 adaptation for replication in the C8166 T cell line was due to the emergence of variant strains that could use CXCR4. Of two variants, one was dual-tropic and one T-tropic, although both could use CCR5 as well as CXCR4. A single mutation in the start codon of the accessory gene vpu accounted for the T-tropic phenotype of the second variant, indicating that a non-functional vpu impairs macrophage tropism. Thus, in vitro and in the absence of an immune response, R5 strains naturally adapt to infect CXCR4+ T cell lines. Such adaptation resembles the rare R5 to X4 switch that occurs in vivo. Mutations in accessory genes (e.g., vpu) not required for replication in rapidly dividing cell lines may also occur in vitro, abrogating replication in primary cell types such as macrophages. Such mutations, however, are normally selected against in vivo.

  11. Mutation of p53 gene codon 63 in saliva as a molecular marker for oral squamous cell carcinomas.

    Science.gov (United States)

    Liao, P H; Chang, Y C; Huang, M F; Tai, K W; Chou, M Y

    2000-05-01

    The inactivation of tumor suppressor gene (TSG) is important during multistage carcinogenesis. The p53 TSG is frequently mutated in oral squamous cell carcinomas. These mutations can serve as very specific markers for the presence of tumor cells in a background of normal cells. In this study, 10 oral squamous cell carcinoma patients and 27 normal dental students were collected from Chung Shan Medical and Dental College Hospital, Taichung, Taiwan. Extractions of DNA from saliva were obtained. Exon 4 and intron 6 within the p53 gene were amplified with polymerase chain reactions (PCRs) followed by DNA sequence analysis. DNA sequence analysis of PCR products revealed that five of eight (62.5%) tumor saliva samples and five of 27 (18. 52%) healthy saliva samples contained p53 exon 4 codon 63 mutations. These results were significantly different by using Chi-square test (Psaliva might be a molecular marker for oral squamous cell carcinomas. In addition, the amount of DNA recovered from saliva in most cases is sufficiently large and its quality suitable to enable PCR amplification which could be used in the search for mutations. The protocol described is rapid, cheap, and easy to perform, and may be useful for epidemiological studies for oral carcinogenesis.

  12. Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

    Science.gov (United States)

    Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

    2014-08-01

    Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

  13. Impulsive alcohol-related risk-behavior and emotional dysregulation among individuals with a serotonin 2B receptor stop codon

    Science.gov (United States)

    Tikkanen, R; Tiihonen, J; Rautiainen, M R; Paunio, T; Bevilacqua, L; Panarsky, R; Goldman, D; Virkkunen, M

    2015-01-01

    A relatively common stop codon (Q20*) was identified in the serotonin 2B receptor gene (HTR2B) in a Finnish founder population in 2010 and it was associated with impulsivity. Here we examine the phenotype of HTR2B Q20* carriers in a setting comprising 14 heterozygous HTR2B Q20* carriers and 156 healthy controls without the HTR2B Q20*. The tridimensional personality questionnaire, Brown–Goodwin lifetime aggression scale, the Michigan alcoholism screening test and lifetime drinking history were used to measure personality traits, impulsive and aggressive behavior, both while sober and under the influence of alcohol, and alcohol consumption. Regression analyses showed that among the HTR2B Q20* carriers, temperamental traits resembled a passive-dependent personality profile, and the presence of the HTR2B Q20* predicted impulsive and aggressive behaviors particularly under the influence of alcohol. Results present examples of how one gene may contribute to personality structure and behaviors in a founder population and how personality may translate into behavior. PMID:26575222

  14. c-Ha-ras BamHI RFLP in human urothelial tumors and point mutations in hot codons

    International Nuclear Information System (INIS)

    Weismanova, E; Skovraga, M.; Kaluz, S.

    1993-01-01

    High-molecular weights DNAs from 30 bladder and renal cell carcinomas (RCC) were isolated and the c-Ha-ras the c-Ha-ras gene BamHI RFLP was examined. Amplification of c-Ha-ras with normal localization with regard to the size of alleles was found only in the case. One of the normally localized c-Ha-ras allele termed RCC c-H-ras of a length of about 6.6 kbp was cloned and an oncogene-activating point mutation was identified using two restriction enzymes. After comparison of CfrI and Cfr10I cleavage maps of RCC c-Ha-ras to complete nucleotide sequences of EJ/T24 c-Ha-ras oncogene and its normal counterpart, a point mutation was identified within codon 11 or 12. The use of CfrI and Cfr10I is of value for clinical practice in identification of point mutations in c-Ha-ras PCR product in neoplasia accompanied by somatic mutation of c-Ha-ras. The correlation among c-Ha-ras allele, amplification/loss, presence of point mutation and progression of neoplasia is discussed. (author)

  15. Introducing COCOS: codon consequence scanner for annotating reading frame changes induced by stop-lost and frame shift variants.

    Science.gov (United States)

    Butkiewicz, Mariusz; Haines, Jonathan L; Bush, William S

    2017-05-15

    Reading frame altering genomic variants can impact gene expression levels and the structure of protein products, thus potentially inducing disease phenotypes. Current annotation approaches report the impact of such variants in the context of altered DNA sequence only; attributes of the resulting transcript, reading frame and translated protein product are not reported. To remedy this shortcoming, we present a new genetic annotation approach termed Codon Consequence Scanner (COCOS). Implemented as an Ensembl variant effect predictor (VEP) plugin, COCOS captures amino acid sequence alterations stemming from variants that produce an altered reading frame, such as stop-lost variants and small insertions and deletions (InDels). To highlight its significance, COCOS was applied to data from the 1000 Genomes Project. Transcripts affected by stop-lost variants introduce a median of 15 amino acids, while InDels have a more extensive impact with a median of 66 amino acids being incorporated. Captured sequence alterations are written out in FASTA format and can be further analyzed for impact on the underlying protein structure. COCOS is available to all users on github: https://github.com/butkiem/COCOS. mariusz.butkiewicz@case.edu. © The Author 2017. Published by Oxford University Press.

  16. Structural Evidence for a Germline-Encoded T Cell Receptor - Major Histocompatibility Complex Interaction 'Codon'

    Energy Technology Data Exchange (ETDEWEB)

    Feng, D.; Bond, C.J.; Ely, L.K.; Maynard, J.; Garcia, K.C.

    2009-06-02

    All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable {beta}-chain 8.2 (V{sub {beta}}8.2), each bound to the MHC class II molecule I-A{sup u}, and did energetic mapping of V{sub {alpha}} and V{sub {beta}} contacts with I-A{sup u}. Together with two previously solved structures of V{sub {beta}}8.2-containing TCR-MHC complexes, we found four TCR-I-A complexes with structurally superimposable interactions between the V{sub {beta}} loops and the I-A {alpha}-helix. This examination of a narrow 'slice' of the TCR-MHC repertoire demonstrates what is probably one of many germline-derived TCR-MHC interaction 'codons'.

  17. Adaptive sequential controller

    Energy Technology Data Exchange (ETDEWEB)

    El-Sharkawi, Mohamed A. (Renton, WA); Xing, Jian (Seattle, WA); Butler, Nicholas G. (Newberg, OR); Rodriguez, Alonso (Pasadena, CA)

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  18. Adaptive sequential controller

    Science.gov (United States)

    El-Sharkawi, Mohamed A.; Xing, Jian; Butler, Nicholas G.; Rodriguez, Alonso

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  19. Adaptive management

    DEFF Research Database (Denmark)

    Rist, Lucy; Campbell, Bruce Morgan; Frost, Peter

    2013-01-01

    a management framework, as well as of identified challenges and pathologies, are needed. Further discussion and systematic assessment of the approach is required, together with greater attention to its definition and description, enabling the assessment of new approaches to managing uncertainty, and AM itself.......Adaptive management (AM) emerged in the literature in the mid-1970s in response both to a realization of the extent of uncertainty involved in management, and a frustration with attempts to use modelling to integrate knowledge and make predictions. The term has since become increasingly widely used...... in scientific articles, policy documents and management plans, but both understanding and application of the concept is mixed. This paper reviews recent literature from conservation and natural resource management journals to assess diversity in how the term is used, highlight ambiguities and consider how...

  20. Genetic variation in codons 167, 198 and 200 of the beta-tubulin gene in whipworms (Trichuris spp.) from a range of domestic animals and wildlife

    DEFF Research Database (Denmark)

    Hansen, Tina Vicky Alstrup; Nejsum, Peter; Olsen, Annette

    2013-01-01

    : 17, dog: 19 and Arabian camels: 14. A pooled sample of Trichuris eggs from 3 moose was also used. In order to amplify the beta-tubulin fragments which covered codons 167, 198 and 200 of the gene, degenerate primers were designed. The sequences obtained were used to design species specific primers......A recurrent problem in the control of whipworm (Trichuris spp.) infections in many animal species and man is the relatively low efficacy of treatment with a single application of benzimidazoles (BZs). The presence of single nucleotide polymorphisms (SNPs) in codons 167, 198 and 200 in the beta...... to investigate the presence of these SNPs in the beta-tubulin gene of Trichuris spp. obtained from a range of animals. DNA was extracted from a total of 121 Trichuris spp. adult whipworm specimens obtained from 6 different host species. The number of worms from each host was pig: 31, deer: 21, sheep: 18, mouse...

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

    Science.gov (United States)

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

    2005-06-15

    In the context of DNA vaccines the native equine infectious anemia virus (EIAV)-envelope gene has proven to be an extremely weak immunogen in horses probably because the RNA transcripts are poorly expressed owing to an unusual codon-usage bias, the possession of multiple RNA splice sites and potential adenosine-rich RNA instability elements. To overcome these problems a synthetic version of sequences encoding the EIAV surface unit (SU) envelope glycoprotein was produced (SYNSU) in which the codon-usage bias was modified to conform to that of highly expressed horse and human genes. In transfected COS-1 cell cultures, the steady state expression levels of SYNSU were at least 30-fold greater than equivalent native SU sequences. More importantly, EIAV-specific humoral and lymphocyte proliferation responses were induced in ponies immunized with a mammalian expression vector encoding SYNSU. However, these immunological responses were unable to confer protection against infection with a virulent EIAV strain.

  2. Increased Prevalence of the pfdhfr/phdhps Quintuple Mutant and Rapid Emergence of pfdhps Eesistance Mutations at Codons 581 and 613 in Kisumu, Kenya

    Science.gov (United States)

    2010-11-24

    pfmdr1. The pfcrt mutation K76T is sufficient for CQ resistance [25]. The pfmdr1 mutation N86Y is linked with CQ resistance and mefloquine ...sensitivity [26-27]. In contrast, quinine and mefloquine resistance are associated with parasites that are wild-type at codon 86, but have increased pfmdr1...associated with increased in vitro resistance to quinine and increased susceptibility to mefloquine and artemisinin [28]. In vivo, treatment with AL selects

  3. Clinical manufacturing of recombinant human interleukin 15. I. Production cell line development and protein expression in E. coli with stop codon optimization.

    Science.gov (United States)

    Vyas, Vinay V; Esposito, Dominic; Sumpter, Terry L; Broadt, Trevor L; Hartley, James; Knapp, George C; Cheng, Wei; Jiang, Man-Shiow; Roach, John M; Yang, Xiaoyi; Giardina, Steven L; Mitra, George; Yovandich, Jason L; Creekmore, Stephen P; Waldmann, Thomas A; Zhu, Jianwei

    2012-01-01

    Interleukin 15 (IL-15) has shown remarkable biological properties of promoting NK- and T-cell activation and proliferation, as well as enhancing antitumor immunity of CD8(+) T cells in preclinical models. Here, we report the development of an E. coli cell line to express recombinant human Interleukin-15 (rhIL-15) for clinical manufacturing. Human IL-15 cDNA sequence was inserted into a pET28b plasmid and expressed in several E. coli BL21 strains. Through product quality comparisons among several E. coli strains, including E. coli BL21(DE3), BL21(DE3)pLysS, BLR(DE3)pLysS, and BL21-AI, E. coli BL21-AI was selected for clinical manufacturing. Expression optimization was carried out at shake flask and 20-L fermenter scales, and the product was expressed as inclusion bodies that were solubilized, refolded, and purified to yield active rhIL-15. Stop codons of the expression construct were further investigated after 15-20% of the purified rhIL-15 showed an extraneous peak corresponding to an extra tryptophan residue based on peptide mapping and mass spectrometry analysis. It was determined that the presence of an extra tryptophan was due to a stop codon wobble effect, which could be eliminated by replacing TGA (opal) stop codon with TAA (ochre). As a novel strategy, a simple method of demonstrating lack of tRNA suppressors in the production host cells was developed to validate the cells in this study. The E. coli BL21-AI cells containing the rhIL-15 coding sequence with a triplet stop codon TAATAATGA were banked for further clinical manufacturing. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

  4. AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo.

    Science.gov (United States)

    Butler, J S; Springer, M; Grunberg-Manago, M

    1987-06-01

    We previously showed that Escherichia coli translation initiation factor IF3 regulates the expression of its own gene infC at the translational level in vivo. Here we create two alterations in the infC gene and test their effects on translational autocontrol of infC expression in vivo by measuring beta-galactosidase activity expressed from infC-lacZ gene fusions under conditions of up to 4-fold derepression or 3-fold repression of infC expression. Replacement of the infC promoter with the trp promoter deletes 120 nucleotides of the infC mRNA 5' to the translation initiation site without affecting autogenous translational control. Mutation of the unusual AUU initiator codon of infC to the more common AUG initiator codon abolishes translation initiation factor IF3-dependent repression and derepression of infC expression in vivo. These results establish the AUU initiator codon of infC as an essential cis-acting element in autogenous translational control of translation initiation factor IF3 expression in vivo.

  5. HP-PRRSV is attenuated by de-optimization of codon pair bias in its RNA-dependent RNA polymerase nsp9 gene.

    Science.gov (United States)

    Gao, Li; Wang, Lianghai; Huang, Chen; Yang, Longlong; Guo, Xue-Kun; Yu, Zhibin; Liu, Yihao; Yang, Peng; Feng, Wen-Hai

    2015-11-01

    There is an urgent need to develop new vaccines against highly pathogenic PRRS virus (HP-PRRSV) variant in China. The actual use of each codon pairs is more or less frequent than that of the statistical prediction and codon pair bias (CPB) usage affects gene translation. We "shuffled" the existing codons in HP-PRRSV genes GP5, M, nsp2 and nsp9, so that the CPB of these genes could be more negative. De-optimization of nsp9, the RNA-dependent RNA polymerase, significantly decreased PRRSV replication in porcine alveolar macrophages (PAMs). In vitro study showed that HV-nsp9(min) and HV-nsp29(min) were remarkably attenuated in PAMs, and inoculation of pigs with 2 ml⁎10(5.0) TCID50/ml of HV-nsp9(min) or HV-nsp29(min) did not cause PRRS. Importantly, pigs immunized with HV-nsp29(min) were fully protected against different HP-PRRSV strains׳ lethal challenges. Our results imply that the CPB de-optimized HV-nsp29(min) has the potential to be used as a live vaccine candidate against HP-PRRSV. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. The adaptation to climate change

    International Nuclear Information System (INIS)

    Van Gameren, Valentine; Weikmans, Romain; Zaccai, Edwin

    2014-01-01

    The authors address the issue of adaptation to climate change. They first address the physical aspects related to this issue: scenarios of temperature evolution, main possible impacts. Then, they address the social impacts related to climate risks, and the adaptation strategies which aim at reducing the exposure and vulnerability of human societies, or at increasing their resilience. Some examples of losses of human lives and of economic damages due to recent catastrophes related to climate change are evoked. The authors address the international framework, the emergence of an international regime on climate, the quite recent emergence of adaptation within international negotiations in 2001, the emergence of the idea of a support to developing countries. National and local policies are presented in the next chapter (in the European Union, the Netherlands which are faced with the issue of sea level rise, programs in developing countries) and their limitations are also outlined. The next chapter addresses the adaptation actions performed by private actors (enterprises, households, associations, civil society, and so on) with example of vulnerability, and adaptation opportunities and possibilities in some specific sectors. The last chapter presents a typology of actions of adaptation, indicators of adaptation to climate change, and examples of mistaken adaptation

  7. Serological and genetic characterisation of bovine respiratory syncytial virus (BRSV) indicates that Danish isolates belong to the intermediate subgroup: no evidence of a selective effect on the variability of G protein nucleotide sequence by prior cell culture adaption and passages in cell culture

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Uttenthal, Åse; Arctander, P.

    1998-01-01

    , respectively. Phylogenetic analysis showed that the Danish isolates formed three lineages within a separate branch of the phylogenetic tree. Nevertheless, the Danish isolates were closely related to the 220-69Bel isolate, the prototype of the intermediate antigenic subgroup. The sequencing of the extracellular...... part of the G gene of additional 11 field BRSV viruses, processed directly from lung samples without prior adaption to cell culture growth. revealed sequence variabilities in the range obtained with the propagated virus. In addition, several passages in cell culture and in calves had no major impact...... on the nucleotide sequence of the G protein. These findings indicated that the previously established variabilities of the G protein of RS virus isolates were not attributable to mutations induced during the propagation of the virus. The reactivity of the Danish isolates with G protein-specific MAbs were similar...

  8. Temporal specificity of the initial adaptive response in motor adaptation.

    Directory of Open Access Journals (Sweden)

    Wilsaan M Joiner

    2017-07-01

    Full Text Available Repeated exposure to a novel physical environment eventually leads to a mature adaptive response whereby feedforward changes in motor output mirror both the amplitude and temporal structure of the environmental perturbations. However, adaptive responses at the earliest stages of learning have been found to be not only smaller, but systematically less specific in their temporal structure compared to later stages of learning. This observation has spawned a lively debate as to whether the temporal structure of the initial adaptive response is, in fact, stereotyped and non-specific. To settle this debate, we directly measured the adaptive responses to velocity-dependent and position-dependent force-field perturbations (vFFs and pFFs at the earliest possible stage of motor learning in humans-after just a single-movement exposure. In line with previous work, we found these earliest stage adaptive responses to be more similar than the perturbations that induced them. However, the single-trial adaptive responses for vFF and pFF perturbations were clearly distinct, and the disparity between them reflected the difference between the temporal structure of the perturbations that drove them. Critically, we observed these differences between single-trial adaptive responses when vFF and pFF perturbations were randomly intermingled from one trial to the next within the same block, indicating perturbation response specificity at the single trial level. These findings demonstrate that the initial adaptive responses to physical perturbations are not stereotyped. Instead, the neural plasticity in sensorimotor areas is sensitive to the temporal structure of a movement perturbation even at the earliest stage in learning. This insight has direct implications for the development of computational models of early-stage motor adaptation and the evolution of this adaptive response with continued training.

  9. A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome.

    Science.gov (United States)

    Matagne, Valerie; Ehinger, Yann; Saidi, Lydia; Borges-Correia, Ana; Barkats, Martine; Bartoli, Marc; Villard, Laurent; Roux, Jean-Christophe

    2017-03-01

    Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent cause of intellectual disability in girls and there is currently no cure for the disease. The finding that the deficits caused by the loss of Mecp2 are reversible in the mouse has bolstered interest in gene therapy as a cure for RTT. In order to assess the feasibility of gene therapy in a RTT mouse model, and in keeping with translational goals, we investigated the efficacy of a self-complementary AAV9 vector expressing a codon-optimized version of Mecp2 (AAV9-MCO) delivered via a systemic approach in early symptomatic Mecp2-deficient (KO) mice. Our results show that AAV9-MCO administered at a dose of 2×10 11 viral genome (vg)/mouse was able to significantly increase survival and weight gain, and delay the occurrence of behavioral deficits. Apneas, which are one of the core RTT breathing deficits, were significantly decreased to WT levels in Mecp2 KO mice after AAV9-MCO administration. Semi-quantitative analysis showed that AAV9-MCO administration in Mecp2 KO mice resulted in 10 to 20% Mecp2 immunopositive cells compared to WT animals, with the highest Mecp2 expression found in midbrain regions known to regulate cardio-respiratory functions. In addition, we also found a cell autonomous increase in tyrosine hydroxylase levels in the A1C1 and A2C2 catecholaminergic Mecp2+ neurons in treated Mecp2 KO mice, which may partly explain the beneficial effect of AAV9-MCO administration on apneas occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Codon optimization of xylA gene for recombinant glucose isomerase production in Pichia pastoris and fed-batch feeding strategies to fine-tune bioreactor performance.

    Science.gov (United States)

    Ata, Özge; Boy, Erdem; Güneş, Hande; Çalık, Pınar

    2015-05-01

    The objectives of this work are the optimization of the codons of xylA gene from Thermus thermophilus to enhance the production of recombinant glucose isomerase (rGI) in P. pastoris and to investigate the effects of feeding strategies on rGI production. Codons of xylA gene from T. thermophilus were optimized, ca. 30 % of the codons were replaced with those with higher frequencies according to the codon usage bias of P. pastoris, codon optimization resulted in a 2.4-fold higher rGI activity. To fine-tune bioreactor performance, fed-batch bioreactor feeding strategies were designed as continuous exponential methanol feeding with pre-calculated feeding rate based on the pre-determined specific growth rate, and fed-batch methanol-stat feeding. Six feeding strategies were designed, as follows: (S1) continuous exponential methanol- and pulse- sorbitol feeding; (S2) continuous exponential methanol- and peptone- feeding; (S3) continuous exponential methanol- and pulse- mannitol feeding; (S4) continuous exponential methanol- and peptone- feeding and pulse-mannitol feeding; (S5) methanol-stat feeding by keeping methanol concentration at 5 g L(-1); and, (S6) methanol-stat feeding by keeping methanol concentration at 5 g L(-1) and pulse-mannitol feeding. The highest cell and rGI activity was attained as 117 g L(-1) at t = 66 h and 32530 U L(-1) at t = 53 h, in strategy-S5. The use of the co-substrate mannitol does not increase the rGI activity in methanol-stat feeding, where 4.1-fold lower rGI activity was obtained in strategy-S6. The overall cell yield on total substrate was determined at t = 53 h as 0.21 g g(-1) in S5 strategy.

  11. Note of clarification of data in the paper titled X-ray repair cross-complementing group 1 codon 399 polymorphism and lung cancer risk: an updated meta-analysis.

    Science.gov (United States)

    Zhai, Wenlong; Feng, Ruo; Wang, Haiyu; Wang, Yadong

    2015-05-01

    We read with great interest the paper titled "X-ray repair cross-complementing group 1 codon 399 polymorphism and lung cancer risk: an updated meta-analysis" published by Wang et al in Tumor Biology, 2014, 35:411-418. Their results suggest that codon 399 polymorphism of XRCC1 gene might contribute to individual's susceptibility to lung cancer in Asian population and especially in nonsmoking Chinese women. The result is encouraging. Nevertheless, several key issues are worth noticing.

  12. Assessing urban adaptive capacity to climate change.

    Science.gov (United States)

    Araya-Muñoz, Dahyann; Metzger, Marc J; Stuart, Neil; Wilson, A Meriwether W; Alvarez, Luis

    2016-12-01

    Despite the growing number of studies focusing on urban vulnerability to climate change, adaptive capacity, which is a key component of the IPCC definition of vulnerability, is rarely assessed quantitatively. We examine the capacity of adaptation in the Concepción Metropolitan Area, Chile. A flexible methodology based on spatial fuzzy modelling was developed to standardise and aggregate, through a stepwise approach, seventeen indicators derived from widely available census statistical data into an adaptive capacity index. The results indicate that all the municipalities in the CMA increased their level of adaptive capacity between 1992 and 2002. However, the relative differences between municipalities did not change significantly over the studied timeframe. Fuzzy overlay allowed us to standardise and to effectively aggregate indicators with differing ranges and granularities of attribute values into an overall index. It also provided a conceptually sound and reproducible means of exploring the interplay of many indicators that individually influence adaptive capacity. Furthermore, it captured the complex, aggregated and continued nature of the adaptive capacity, favouring to deal with gaps of data and knowledge associated with the concept of adaptive capacity. The resulting maps can help identify municipalities where adaptive capacity is weak and identify which components of adaptive capacity need strengthening. Identification of these capacity conditions can stimulate dialogue amongst policymakers and stakeholders regarding how to manage urban areas and how to prioritise resources for urban development in ways that can also improve adaptive capacity and thus reduce vulnerability to climate change. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Analysis of the relationship between genomic GC Content and patterns of base usage, codon usage and amino acid usage in prokaryotes: similar GC content adopts similar compositional frequencies regardless of the phylogenetic lineages.

    Directory of Open Access Journals (Sweden)

    Hui-Qi Zhou

    Full Text Available The GC contents of 2670 prokaryotic genomes that belong to diverse phylogenetic lineages were analyzed in this paper. These genomes had GC contents that ranged from 13.5% to 74.9%. We analyzed the distance of base frequencies at the three codon positions, codon frequencies, and amino acid compositions across genomes with respect to the differences in the GC content of these prokaryotic species. We found that although the phylogenetic lineages were remote among some species, a similar genomic GC content forced them to adopt similar base usage patterns at the three codon positions, codon usage patterns, and amino acid usage patterns. Our work demonstrates that in prokaryotic genomes: a base usage, codon usage, and amino acid usage change with GC content with a linear correlation; b the distance of each usage has a linear correlation with the GC content difference; and c GC content is more essential than phylogenetic lineage in determining base usage, codon usage, and amino acid usage. This work is exceptional in that we adopted intuitively graphic methods for all analyses, and we used these analyses to examine as many as 2670 prokaryotes. We hope that this work is helpful for understanding common features in the organization of microbial genomes.

  14. Predictive analytics of environmental adaptability in multi-omic network models.

    Science.gov (United States)

    Angione, Claudio; Lió, Pietro

    2015-10-20

    Bacterial phenotypic traits and lifestyles in response to diverse environmental conditions depend on changes in the internal molecular environment. However, predicting bacterial adaptability is still difficult outside of laboratory controlled conditions. Many molecular levels can contribute to the adaptation to a changing environment: pathway structure, codon usage, metabolism. To measure adaptability to changing environmental conditions and over time, we develop a multi-omic model of Escherichia coli that accounts for metabolism, gene expression and codon usage at both transcription and translation levels. After the integration of multiple omics into the model, we propose a multiobjective optimization algorithm to find the allowable and optimal metabolic phenotypes through concurrent maximization or minimization of multiple metabolic markers. In the condition space, we propose Pareto hypervolume and spectral analysis as estimators of short term multi-omic (transcriptomic and metabolic) evolution, thus enabling comparative analysis of metabolic conditions. We therefore compare, evaluate and cluster different experimental conditions, models and bacterial strains according to their metabolic response in a multidimensional objective space, rather than in the original space of microarray data. We finally validate our methods on a phenomics dataset of growth conditions. Our framework, named METRADE, is freely available as a MATLAB toolbox.

  15. Complete genome of the cellulolytic thermophile Acidothermus cellulolyticus 11B provides insights into its ecophysiological and evolutionary adaptations

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Gary [Los Alamos National Laboratory; Detter, Chris [Los Alamos National Laboratory; Bruce, David [Los Alamos National Laboratory; Challacome, Jean F [Los Alamos National Laboratory; Brettin, Thomas S [Los Alamos National Laboratory; Barabote, Ravi D [UC DAVIS; Leu, David [UC DAVIS; Normand, Philippe [CNRS, UNIV LYON; Necsula, Anamaria [CNRS, UNIV LYON; Daubin, Vincent [CNRS, UNIV LYON; Medigue, Claudine [CNRS/GENOSCOPE; Adney, William S [NREL; Xu, Xin C [UC DAVIS; Lapidus, Alla [DOE JOINT GENOME INST.; Pujic, Pierre [CNRS, UNIV LYON; Richardson, Paul [DOE JOINT GENOME INST; Berry, Alison M [UC DAVIS

    2008-01-01

    We present here the complete 2.4 MB genome of the actinobacterial thermophile, Acidothermus cellulolyticus lIB, that surprisingly reveals thermophilic amino acid usage in only the cytosolic subproteome rather than its whole proteome. Thermophilic amino acid usage in the partial proteome implies a recent, ongoing evolution of the A. cellulolyticus genome since its divergence about 200-250 million years ago from its closest phylogenetic neighbor Frankia, a mesophilic plant symbiont. Differential amino acid usage in the predicted subproteomes of A. cellulolyticus likely reflects a stepwise evolutionary process of modern thermophiles in general. An unusual occurrence of higher G+C in the non-coding DNA than in the transcribed genome reinforces a late evolution from a higher G+C common ancestor. Comparative analyses of the A. cellulolyticus genome with those of Frankia and other closely-related actinobacteria revealed that A. cellulolyticus genes exhibit reciprocal purine preferences at the first and third codon positions, perhaps reflecting a subtle preference for the dinucleotide AG in its mRNAs, a possible adaptation to a thermophilic environment. Other interesting features in the genome of this cellulolytic, hot-springs dwelling prokaryote reveal streamlining for adaptation to its specialized ecological niche. These include a low occurrence of pseudogenes or mobile genetic elements, a flagellar gene complement previously unknown in this organism, and presence of laterally-acquired genomic islands of likely ecophysiological value. New glycoside hydrolases relevant for lignocellulosic biomass deconstruction were identified in the genome, indicating a diverse biomass-degrading enzyme repertoire several-fold greater than previously characterized, and significantly elevating the industrial value of this organism.

  16. Complete genome of the cellulolytic thermophile Acidothermus cellulolyticus 11B provides insights into its ecophysiological and evolutionary adaptations

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Gary [Los Alamos National Laboratory; Detter, John C [Los Alamos National Laboratory; Bruce, David C [Los Alamos National Laboratory; Challacombe, Jean F [Los Alamos National Laboratory; Brettin, Thomas S [Los Alamos National Laboratory; Necsulea, Anamaria [UNIV LYON; Daubin, Vincent [UNIV LYON; Medigue, Claudine [GENOSCOPE; Adney, William S [NREL; Xu, Xin C [UC DAVIS; Lapidus, Alla [JGI; Pujic, Pierre [UNIV LYON; Berry, Alison M [UC DAVIS; Barabote, Ravi D [UC DAVIS; Leu, David [UC DAVIS; Normand, Phillipe [UNIV LYON

    2009-01-01

    We present here the complete 2.4 MB genome of the actinobacterial thermophile, Acidothermus cellulolyticus 11B, that surprisingly reveals thermophilic amino acid usage in only the cytosolic subproteome rather than its whole proteome. Thermophilic amino acid usage in the partial proteome implies a recent, ongoing evolution of the A. cellulolyticus genome since its divergence about 200-250 million years ago from its closest phylogenetic neighbor Frankia, a mesophilic plant symbiont. Differential amino acid usage in the predicted subproteomes of A. cellulolyticus likely reflects a stepwise evolutionary process of modern thermophiles in general. An unusual occurrence of higher G+C in the non-coding DNA than in the transcribed genome reinforces a late evolution from a higher G+C common ancestor. Comparative analyses of the A. cellulolyticus genome with those of Frankia and other closely-related actinobacteria revealed that A. cellulolyticus genes exhibit reciprocal purine preferences at the first and third codon positions, perhaps reflecting a subtle preference for the dinucleotide AG in its mRNAs, a possible adaptation to a thermophilic environment. Other interesting features in the genome of this cellulolytic, hot-springs dwelling prokaryote reveal streamlining for adaptation to its specialized ecological niche. These include a low occurrence of pseudo genes or mobile genetic elements, a flagellar gene complement previously unknown in this organism, and presence of laterally-acquired genomic islands of likely ecophysiological value. New glycoside hydrolases relevant for lignocellulosic biomass deconstruction were identified in the genome, indicating a diverse biomass-degrading enzyme repertoire several-fold greater than previously characterized, and significantly elevating the industrial value of this organism.

  17. Adaptive Controller Adaptation Time and Available Control Authority Effects on Piloting

    Science.gov (United States)

    Trujillo, Anna; Gregory, Irene

    2013-01-01

    Adaptive control is considered for highly uncertain, and potentially unpredictable, flight dynamics characteristic of adverse conditions. This experiment looked at how adaptive controller adaptation time to recover nominal aircraft dynamics affects pilots and how pilots want information about available control authority transmitted. Results indicate that an adaptive controller that takes three seconds to adapt helped pilots when looking at lateral and longitudinal errors. The controllability ratings improved with the adaptive controller, again the most for the three seconds adaptation time while workload decreased with the adaptive controller. The effects of the displays showing the percentage amount of available safe flight envelope used in the maneuver were dominated by the adaptation time. With the displays, the altitude error increased, controllability slightly decreased, and mental demand increased. Therefore, the displays did require some of the subjects resources but these negatives may be outweighed by pilots having more situation awareness of their aircraft.

  18. Supporting Adaptive and Adaptable Hypermedia Presentation Semantics

    NARCIS (Netherlands)

    D.C.A. Bulterman (Dick); L. Rutledge (Lloyd); L. Hardman (Lynda); J.R. van Ossenbruggen (Jacco)

    1999-01-01

    textabstractHaving the content of a presentation adapt to the needs, resources and prior activities of a user can be an important benefit of electronic documents. While part of this adaptation is related to the encodings of individual data streams, much of the adaptation can/should be guided by the

  19. Analysis of Tp53 codon 72 polymorphisms, Tp53 mutations, and HPV infection in cutaneous squamous cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Keith R Loeb

    Full Text Available Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism.We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.These studies suggest there are two separate pathways (HPV infection and Tp53 mutation leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly

  20. The effect of gentamicin-induced readthrough on a novel premature termination codon of CD18 leukocyte adhesion deficiency patients.

    Directory of Open Access Journals (Sweden)

    Amos J Simon

    2010-11-01

    Full Text Available Leukocyte adhesion deficiency 1 (LAD1 is an inherited disorder of neutrophil function. Nonsense mutations in the affected CD18 (ITB2 gene have rarely been described. In other genes containing such mutations, treatments with aminoglycoside types of antibiotics (e.g., gentamicin were reported to partially correct the premature protein termination, by induction of readthrough mechanism.Genetic analysis was performed on 2 LAD1 patients. Expression, functional and immunofluorescence assays of CD18 in the patients were used to determine the in-vivo and in-vitro effects of gentamicin-induced readthrough. A theoretical modeling of the corrected CD18 protein was developed to predict the protein function.We found a novel premature termination codon, C562T (R188X, in exon 6 of the CD18 gene that caused a severe LAD1 phenotype in two unrelated Palestinian children. In-vivo studies on these patients' cells after gentamicin treatment showed abnormal adhesion and chemotactic functions, while in-vitro studies showed mislocalization of the corrected protein to the cytoplasm and not to the cell surface. A theoretical modeling of the corrected CD18 protein suggested that the replacement of the wild type arginine by gentamicin induced tryptophan at the position of the nonsense mutation, although enabled the expression of the entire CD18 protein, this was not sufficient to stabilize the CD18/11 heterodimer at the cell surface.A novel nonsense mutation in the CD18 gene causing a complete absence of CD18 protein and severe LAD1 clinical phenotype is reported. Both in vivo and in vitro treatments with gentamicin resulted in the expression of a corrected full-length dysfunctional or mislocalized CD18 protein. However, while the use of gentamicin increased the expression of CD18, it did not improve leukocyte adhesion and chemotaxis. Moreover, the integrity of the CD18/CD11 complex at the cell surface was impaired, due to abnormal CD18 protein and possibly lack of CD11a

  1. The p53 codon 72 PRO/PRO genotype may be associated with initial central visual field defects in caucasians with primary open angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Janey L Wiggs

    Full Text Available Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg and the subset of primary open angle glaucoma (POAG patients with early loss of central visual field.Genotypes for the p53 codon 72 polymorphism (Pro/Arg were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST. The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral. All cases and controls were Caucasian with European ancestry.The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p=2.7 × 10(-5. We replicated this finding in the GIST cohort (p  =7.3 × 10(-3, and in the pooled sample (p=6.6 × 10(-7 and in a meta-analysis of both the US and GIST datasets (1.3 × 10(-6, OR 2.17 (1.58-2.98 for the PRO allele.These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients.

  2. Mycobacterium tuberculosis Is Resistant to Isoniazid at a Slow Growth Rate by Single Nucleotide Polymorphisms in katG Codon Ser315.

    Directory of Open Access Journals (Sweden)

    Rose E Jeeves

    Full Text Available An important aim for improving TB treatment is to shorten the period of antibiotic therapy without increasing relapse rates or encouraging the development of antibiotic-resistant strains. In any M. tuberculosis population there is a proportion of bacteria that are drug-tolerant; this might be because of pre-existing populations of slow growing/non replicating bacteria that are protected from antibiotic action due to the expression of a phenotype that limits drug activity. We addressed this question by observing populations of either slow growing (constant 69.3h mean generation time or fast growing bacilli (constant 23.1h mean generation time in their response to the effects of isoniazid exposure, using controlled and defined growth in chemostats. Phenotypic differences were detected between the populations at the two growth rates including expression of efflux mechanisms and the involvement of antisense RNA/small RNA in the regulation of a drug-tolerant phenotype, which has not been explored previously for M. tuberculosis. Genotypic analyses showed that slow growing bacilli develop resistance to isoniazid through mutations specifically in katG codon Ser315 which are present in approximately 50-90% of all isoniazid-resistant clinical isolates. The fast growing bacilli persisted as a mixed population with katG mutations distributed throughout the gene. Mutations in katG codon Ser315 appear to have a fitness cost in vitro and particularly in fast growing cultures. Our results suggest a requirement for functional katG-encoded catalase-peroxide in the slow growers but not the fast-growing bacteria, which may explain why katG codon Ser315 mutations are favoured in the slow growing cultures.

  3. Evolution of type 2 vaccine derived poliovirus lineages. Evidence for codon-specific positive selection at three distinct locations on capsid wall.

    Directory of Open Access Journals (Sweden)

    Tapani Hovi

    Full Text Available Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003-2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2 were compared to those of type 1 and type 3 wild poliovirus (WPV lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin by 12.5-15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv bias and strikingly lower Ts/Tv rate ratios at the 2(nd codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2(nd codon position was also found in the large set of VP1 sequences of Nigerian circulating (cVDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.

  4. Evolution of type 2 vaccine derived poliovirus lineages. Evidence for codon-specific positive selection at three distinct locations on capsid wall.

    Science.gov (United States)

    Hovi, Tapani; Savolainen-Kopra, Carita; Smura, Teemu; Blomqvist, Soile; Al-Hello, Haider; Roivainen, Merja

    2013-01-01

    Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003-2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2) were compared to those of type 1 and type 3 wild poliovirus (WPV) lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin) by 12.5-15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv) bias and strikingly lower Ts/Tv rate ratios at the 2(nd) codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2(nd) codon position was also found in the large set of VP1 sequences of Nigerian circulating (c)VDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.

  5. Geomagnetic Indices Bulletin (GIB)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Geomagnetic Indices Bulletin is a one page sheet containing the magnetic indices Kp, Ap, Cp, An, As, Am and the provisional aa indices. The bulletin is published...

  6. Adaptation illustrations: Chapter 4

    Science.gov (United States)

    Maria Janowiak; Patricia Butler; Chris Swanston; Matt St. Pierre; Linda. Parker

    2012-01-01

    In this chapter, we demonstrate how the Adaptation Workbook (Chapter 3) can be used with the Adaptation Strategies and Approaches (Chapter 2) to develop adaptation tactics for two real-world management issues. The two illustrations in this chapter are intended to provide helpful tips to managers completing the Adaptation Workbook, as well as to show how the anticipated...

  7. Sustainable development indicators for cities

    Directory of Open Access Journals (Sweden)

    Sergey Nikolayevich Bobylev

    2014-09-01

    Full Text Available The assessment of urban population’s life quality implies an investigation of all factors defining it: economic, social and ecological. The development of the corresponding indicators of sustainable urban development is necessary. The majority of the cities in the world and this country show unsustainable development at present time. In the article, the world and Russian experience of development of indicators of sustainable urban development is considered. In the article, opportunities of adaptation of approaches to these indicators’ development on the basis of Human Development Index developed by United Nations Development Program and an index of Adjusted Net Savings of the World Bank for Russia are considered. The authors propose a new integrated index of sustainability for Russian cities. It is based on the concept and methodology of the Adjusted Net Savings index. In order to evaluate the sustainability of urban development taking into account economic, social, and ecological factors, the authors propose applying three corresponding sub-indexes: gross capital, expenses on human capital development, and damage from environmental pollution in the cities. In the article, the authors’ set of indicators for Russian cities is proposed. It reflects the most acute problems of sustainable urban development in Russia and the quality of life in cities; also it corresponds to Russian statistics. 21 key indicators reflecting important economic, social, and ecological urban priorities are proposed. Indicators are divided into nine groups: economic indicators; energy efficiency; transport; social and institutional indicators; air and climate; water resources; waste; especially protected natural territories; noise influence. Proposed indicators for cities allow more adequately assess trends of urbanized space shaping and quality of life

  8. Examination of food chain-derived Listeria monocytogenes strains of different serotypes reveals considerable diversity in inlA genotypes, mutability, and adaptation to cold temperatures.

    Science.gov (United States)

    Kovacevic, Jovana; Arguedas-Villa, Carolina; Wozniak, Anna; Tasara, Taurai; Allen, Kevin J

    2013-03-01

    Listeria monocytogenes strains belonging to serotypes 1/2a and 4b are frequently linked to listeriosis. While inlA mutations leading to premature stop codons (PMSCs) and attenuated virulence are common in 1/2a, they are rare in serotype 4b. We observed PMSCs in 35% of L. monocytogenes isolates (n = 54) recovered from the British Columbia food supply, including serotypes 1/2a (30%), 1/2c (100%), and 3a (100%), and a 3-codon deletion (amino acid positions 738 to 740) seen in 57% of 4b isolates from fish-processing facilities. Caco-2 invasion assays showed that two isolates with the deletion were significantly more invasive than EGD-SmR (P cold temperature following a downshift from 37°C to 4°C. Overall, three distinct cold-adapting groups (CAG) were observed: 46% were fast (200 h) adaptors. Intermediate CAG strains (70%) more frequently possessed inlA PMSCs than did fast (20%) and slow (10%) CAGs; in contrast, 87% of fast adaptors lacked inlA PMSCs. In conclusion, we report food chain-derived 1/2a and 4b serotypes with a 3-codon deletion possessing invasive behavior and the novel association of inlA genotypes encoding a full-length InlA with fast cold-adaptation phenotypes.

  9. Adaptive prediction applied to seismic event detection

    International Nuclear Information System (INIS)

    Clark, G.A.; Rodgers, P.W.

    1981-01-01

    Adaptive prediction was applied to the problem of detecting small seismic events in microseismic background noise. The Widrow-Hoff LMS adaptive filter used in a prediction configuration is compared with two standard seismic filters as an onset indicator. Examples demonstrate the technique's usefulness with both synthetic and actual seismic data

  10. Adaptive prediction applied to seismic event detection

    Energy Technology Data Exchange (ETDEWEB)

    Clark, G.A.; Rodgers, P.W.

    1981-09-01

    Adaptive prediction was applied to the problem of detecting small seismic events in microseismic background noise. The Widrow-Hoff LMS adaptive filter used in a prediction configuration is compared with two standard seismic filters as an onset indicator. Examples demonstrate the technique's usefulness with both synthetic and actual seismic data.

  11. Analysis of Adaptive Evolution in Lyssavirus Genomes Reveals Pervasive Diversifying Selection during Species Diversification

    Directory of Open Access Journals (Sweden)

    Carolina M. Voloch

    2014-11-01

    Full Text Available Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. Although numerous studies have examined pattern-related questions concerning Lyssavirus evolution, analyses of the evolutionary processes acting on Lyssavirus diversification are scarce. To clarify the relevance of positive natural selection in Lyssavirus diversification, we conducted a comprehensive scan for episodic diversifying selection across all lineages and codon sites of the five coding regions in lyssavirus genomes. Although the genomes of these viruses are generally conserved, the glycoprotein (G, RNA-dependent RNA polymerase (L and polymerase (P genes were frequently targets of adaptive evolution during the diversification of the genus. Adaptive evolution is particularly manifest in the glycoprotein gene, which was inferred to have experienced the highest density of positively selected codon sites along branches. Substitutions in the L gene were found to be associated with the early diversification of phylogroups. A comparison between the number of positively selected sites inferred along the branches of RABV population branches and Lyssavirus intespecies branches suggested that the occurrence of positive selection was similar on the five coding regions of the genome in both groups.

  12. Digging deeper: new gene order rearrangements and distinct patterns of codons usage in mitochondrial genomes among shrimps from the Axiidea, Gebiidea and Caridea (Crustacea: Decapoda

    Directory of Open Access Journals (Sweden)

    Mun Hua Tan

    2017-03-01

    Full Text Available Background Whole mitochondrial DNA is being increasingly utilized for comparative genomic and phylogenetic studies at deep and shallow evolutionary levels for a range of taxonomic groups. Although mitogenome sequences are deposited at an increasing rate into public databases, their taxonomic representation is unequal across major taxonomic groups. In the case of decapod crustaceans, several infraorders, including Axiidea (ghost shrimps, sponge shrimps, and mud lobsters and Caridea (true shrimps are still under-represented, limiting comprehensive phylogenetic studies that utilize mitogenomic information. Methods Sequence reads from partial genome scans were generated using the Illumina MiSeq platform and mitogenome sequences were assembled from these low coverage reads. In addition to examining phylogenetic relationships within the three infraorders, Axiidea, Gebiidea, and Caridea, we also investigated the diversity and frequency of codon usage bias and mitogenome gene order rearrangements. Results We present new mitogenome sequences for five shrimp species from Australia that includes two ghost shrimps, Callianassa ceramica and Trypaea australiensis, along with three caridean shrimps, Macrobrachium bullatum, Alpheus lobidens, and Caridina cf. nilotica. Strong differences in codon usage were discovered among the three infraorders and significant gene order rearrangements were observed. While the gene order rearrangements are congruent with the inferred phylogenetic relationships and consistent with taxonomic classification, they are unevenly distributed within and among the three infraorders. Discussion Our findings suggest potential for mitogenome rearrangements to be useful phylogenetic markers for decapod crustaceans and at the same time raise important questions concerning the drivers of mitogenome evolution in different decapod crustacean lineages.

  13. A Generalized Michaelis-Menten Equation in Protein Synthesis: Effects of Mis-Charged Cognate tRNA and Mis-Reading of Codon.

    Science.gov (United States)

    Dutta, Annwesha; Chowdhury, Debashish

    2017-05-01

    The sequence of amino acid monomers in the primary structure of a protein is decided by the corresponding sequence of codons (triplets of nucleic acid monomers) on the template messenger RNA (mRNA). The polymerization of a protein, by incorporation of the successive amino acid monomers, is carried out by a molecular machine called ribosome. We develop a stochastic kinetic model that captures the possibilities of mis-reading of mRNA codon and prior mis-charging of a tRNA. By a combination of analytical and numerical methods, we obtain the distribution of the times taken for incorporation of the successive amino acids in the growing protein in this mathematical model. The corresponding exact analytical expression for the average rate of elongation of a nascent protein is a 'biologically motivated' generalization of the Michaelis-Menten formula for the average rate of enzymatic reactions. This generalized Michaelis-Menten-like formula (and the exact analytical expressions for a few other quantities) that we report here display the interplay of four different branched pathways corresponding to selection of four different types of tRNA.

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

    Science.gov (United States)

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

    2012-01-15

    Order Chiroptera is a unique group of mammals whose members have attained self-powered flight as their main mode of locomotion. Much speculation persists regarding bat evolution; however, lack of sufficient molecular data hampers evolutionary and conservation studies. Of ~1200 species, complete mitochondrial genome sequences are available for only eleven. Additional sequences should be generated if we are to resolve many questions concerning these fascinating mammals. Herein, we describe the complete mitochondrial genomes of three bats: Corynorhinus rafinesquii, Lasiurus borealis and Artibeus lituratus. We also compare the currently available mitochondrial genomes and analyze codon usage in Chiroptera. C. rafinesquii, L. borealis and A. lituratus mitochondrial genomes are 16438 bp, 17048 bp and 16709 bp, respectively. Genome organization and gene arrangements are similar to other bats. Phylogenetic analyses using complete mitochondrial genome sequences support previously established phylogenetic relationships and suggest utility in future studies focusing on the evolutionary aspects of these species. Comprehensive analyses of available bat mitochondrial genomes reveal distinct nucleotide patterns and synonymous codon preferences corresponding to different chiropteran families. These patterns suggest that mutational and selection forces are acting to different extents within Chiroptera and shape their mitochondrial genomes. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. A PCR-mutagenesis strategy for rapid detection of mutations in codon 634 of the ret proto-oncogene related to MEN 2A.

    Directory of Open Access Journals (Sweden)

    Godoy Clara

    2002-05-01

    Full Text Available Abstract Background Multiple endocrine neoplasias type 2A (MEN 2A is a dominantly inherited cancer syndrome. Missence mutations in the codon encoding cysteine 634 of the ret proto-oncogene have been found in 85% of the MEN 2A families. The main tumour type always present in MEN 2A is medullar thyroid carcinoma (MTC. Only 25% of all MTC are hereditary, and generally they are identified by a careful family history. However, some familial MTCs are not easily detected by this means and underdiagnosis of MEN 2A is suspected. Methods DNA samples from MEN 2A patients were amplified by PCR. The products were incubated with the restriction enzyme Bst ApI or Bgl I. The samples were loaded in non-denaturing 10% Polyacrilamyde Gel and run at 120 volts for 40 min. The gels were stained with 10 μg/ml ethidium bromide, and the bands were visualized under a UV lamp. Results We developed a PCR-mutagenic method to check the integrity of the three bases of the cysteine 634 codon. Conclusion The method can be used to detect inherited mutations in MTC patients without a clear family history. The method is relatively simple to use as a routine test in these patients to decrease the underdiagnosis of MEN 2A. In addition, the assay can be used to screen affected families with any mutation in cysteine 634.

  16. Atypical radiological findings in achondroplasia with uncommon mutation of the fibroblast growth factor receptor-3 (FGFR-3) gene (Gly to Cys transition at codon 375)

    Energy Technology Data Exchange (ETDEWEB)

    Nishimuri, Gen [Dokkyo Univ. School of Medicine, Tochigi (Japan); Fukushima, Yoshimitsu; Ohashi, Hirofumi [Saitama Children`s Medical Center, Saitama (Japan); Ikegawa, Shiro [Tokyo Univ. (Japan)

    1995-11-20

    The recent discovery of mutations in the FGFR-3 (fibroblast growth factor receptor-3) gene (FGFR3) as the cause of achondroplasia has provided new insight into understanding genetic diseases. It was surprising from the viewpoint of molecular genetics that most patients with achondroplasia showed the same mutation at nucleotide 1138, leading to a single amino acid substitution from glycine to arginine at codon 380 (Gly380Arg). All 39 patients examined by two groups had the Gly380Arg; 38 patients and the other demonstrated a G to A and a G to C transition at nucleotide 1138, respectively. Subsequently another group disclosed a G to A transition at the same nucleotide 1138 in 21/23 patients of diverse ethnic origin, although mutations were not identified in two patients. To date, a total of 193 patients with the mutation of the G380Arg have been reported; a single patient with another mutation resulting in a substitution from glycine to cysteine at codon 375 (Gly375Cys) has been described. The presence of this common mutation is consistent with the clinical fact that achondroplastic individuals show less phenotypic variability than is unusual for autosomal dominant diseases. We encountered a Japanese boy with the Gly375Cys. His mother with achondroplasia has the same mutation. The molecular investigation of these patients was reported elsewhere. Here we report the clinical and radiological findings in this boy who demonstrated some atypical manifestations from those of typical achondroplasia. 8 refs., 1 fig.

  17. Characterisation of heteroplasmic status at codon 143 of the Botrytis cinerea cytochrome b gene in a semi-quantitative AS-PCR assay.

    Science.gov (United States)

    Hashimoto, Maki; Aoki, Yoshinao; Saito, Seiya; Suzuki, Shunji

    2015-03-01

    An in-depth understanding of quinone outside inhibitor (QoI)-fungicide-resistant Botrytis cinerea isolates in a vineyard is expected to contribute to the development of an optimum disease management programme for the control of grape grey mould. The resistance and structure of the cytochrome b gene in B. cinerea collected from a Japanese vineyard were characterised. The semi-quantitative allele-specific primer-polymerase chain reaction (AS-PCR) assay developed in the present study was able to distinguish heteroplasmic status from homoplasmic status at codon 143 of the cytochrome b gene in QoI-fungicide-resistant B. cinerea from vineyards in Japan. With this assay it was demonstrated that the repeated introduction of QoI fungicide selection pressure increased the ratio of G143A-mutated cytochrome b genes in B. cinerea isolates. It is proposed that the semi-quantitative AS-PCR assay is a reliable tool for the detection of QoI fungicide resistance and the evaluation of homoplasmic/heteroplasmic status at codon 143 of the cytochrome b gene in B. cinerea isolates. © 2014 Society of Chemical Industry.

  18. Comparative analyses of codon and amino acid usage in symbiotic island and core genome in nitrogen-fixing symbiotic bacterium Bradyrhizobium japonicum.

    Science.gov (United States)

    Das, Sabyasachi; Pan, Archana; Paul, Sandip; Dutta, Chitra

    2005-10-01

    Genes involved in the symbiotic interactions between the nitrogen-fixing endosymbiont Bradyrhizobium japonicum, and its leguminous host are mostly clustered in a symbiotic island (SI), acquired by the bacterium through a process of horizontal transfer. A comparative analysis of the codon and amino acid usage in core and SI genes/proteins of B. japonicum has been carried out in the present study. The mutational bias, translational selection, and gene length are found to be the major sources of variation in synonymous codon usage in the core genome as well as in SI, the strength of translational selection being higher in core genes than in SI. In core proteins, hydrophobicity is the main source of variation in amino acid usage, expressivity and aromaticity being the second and third important sources. But in SI proteins, aromaticity is the chief source of variation, followed by expressivity and hydrophobicity. In SI proteins, both the mean molecular weight and mean aromaticity of individual proteins exhibit significant positive correlation with gene expressivity, which violate the cost-minimization hypothesis. Investigation of nucleotide substitution patterns in B. japonicum and Mesorhizobium loti orthologous genes reveals that both synonymous and non-synonymous sites of highly expressed genes are more conserved than their lowly expressed counterparts and this conservation is more pronounced in the genes present in core genome than in SI.

  19. CREDIT Performance Indicator Framework

    DEFF Research Database (Denmark)

    Frandsen, Anne Kathrine; Bertelsen, Niels Haldor; Haugbølle, Kim

    2010-01-01

    was a framework of indicators relevant in building and real estate and applicable in the Nordic and Baltic countries as well as a proposal for a set of key indicators. The study resulting in CREDIT Performance Indicator Framework has been based on 28 case studies of evaluation practises in the building and real...... regulations in the countries participating in CREDIT. The Performance Indicator Framework encompassed 187 indicators grouped in 7 main groups of indicators and 42 sub-groups. Based on the CREDIT case studies it was concluded that there neither is link between certain indicators and specific building types...

  20. Expressing Adaptation Strategies Using Adaptation Patterns

    Science.gov (United States)

    Zemirline, N.; Bourda, Y.; Reynaud, C.

    2012-01-01

    Today, there is a real challenge to enable personalized access to information. Several systems have been proposed to address this challenge including Adaptive Hypermedia Systems (AHSs). However, the specification of adaptation strategies remains a difficult task for creators of such systems. In this paper, we consider the problem of the definition…

  1. Time-adaptive quantile regression

    DEFF Research Database (Denmark)

    Møller, Jan Kloppenborg; Nielsen, Henrik Aalborg; Madsen, Henrik

    2008-01-01

    An algorithm for time-adaptive quantile regression is presented. The algorithm is based on the simplex algorithm, and the linear optimization formulation of the quantile regression problem is given. The observations have been split to allow a direct use of the simplex algorithm. The simplex method...... and an updating procedure are combined into a new algorithm for time-adaptive quantile regression, which generates new solutions on the basis of the old solution, leading to savings in computation time. The suggested algorithm is tested against a static quantile regression model on a data set with wind power...... production, where the models combine splines and quantile regression. The comparison indicates superior performance for the time-adaptive quantile regression in all the performance parameters considered....

  2. Animal Communication and Its Cognitive Indications.

    Science.gov (United States)

    McLean, Laura L.

    Various examples of communication in species ranging from bumble bees to dolphins are examined in this paper. Focus is directed to indications of the cognitive ability of each species. The signals of cognition include evidence of: adaptability to a new situation; long term memory; and the property of displacement. Most of the sources reviewed…

  3. UV "Indices"-What Do They Indicate?

    Science.gov (United States)

    Moshammer, Hanns; Simic, Stana; Haluza, Daniela

    2016-10-24

    Ultra-Violet (UV) radiation covers the spectrum of wavelengths from 100 to 400 nm. The potency and biological activity for a variety of endpoints differ by wavelength. For monitoring and communication purposes, different UV action spectra have been developed. These spectra use different weighting functions. The action spectrum for erythemal dose is the most widely used one. This erythemal dose per time or dose-rate has been further simplified into a "UV index". Following this example, in our review we use the term "index" or (plural) "indices" in a more general description for all simplified single-value measures for any biologically effective UV dose, e.g., for human non-melanoma skin cancer and for previtamin D production rate. Ongoing discussion about the existence of an increased melanoma risk due to UV-A exposure underscores the uncertainties inherent in current weighting functions. Thus, we performed an online literature search to review the data basis for these indices, to understand their relevance for an individual, and to assess the applicability of the indices for a range of exposure scenarios. Even for natural (solar) UV, the spectral composition varies spatially and temporally. Artificial UV sources and personal protection introduce further variation to the spectral composition. Many biological effects are proposed for UV radiation. Only few endpoints have been studied sufficiently to estimate a reliable index. Weighting functions for chronic effects and most importantly for cancer endpoints have been developed in animal models, and often for proxy endpoints only. Epidemiological studies on biological effects of UV radiation should not only depend on single-value weighted UV dose estimates (indexes) but should strive for a more detailed description of the individual exposure. A better understanding of the adverse and beneficial effects of UV radiation by wavelength would also improve medical counseling and health communication regarding individual

  4. Geomagnetic aa Indices

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The geomagnetic aa indices are the continuation of the series beginning in the year 1868. A full description of these indices is given in the International...

  5. The elusive nature of adaptive mitochondrial DNA evolution of an Arctic lineage prone to frequent introgression

    DEFF Research Database (Denmark)

    Melo-Ferreira, Jose; Vilela, Joana; Fonseca, Miguel M.

    2014-01-01

    understood. Hares (Lepus spp.) are privileged models to study the impact of natural selection on mitogenomic evolution because 1) species are adapted to contrasting environments, including arctic, with different metabolic pressures, and 2) mtDNA introgression from arctic into temperate species is widespread....... Here, we analyzed the sequences of 11 complete mitogenomes (ten newly obtained) of hares of temperate and arctic origins (including two of arctic origin introgressed into temperate species). The analysis of patterns of codon substitutions along the reconstructed phylogeny showed evidence for positive...... lie on complex interactions with nuclear encoded peptides. Also, a cloverleaf structure was detected in the control region only from the arctic mtDNA lineage, which may influence mtDNA replication and transcription. These results suggest that adaptation impacted the evolution of hare mtDNA and may...

  6. environmental stress indicators system

    African Journals Online (AJOL)

    EJIRO

    TESs =TELd/As = (DMI+DPO+2HF-I)/As. (7). From the above-mentioned calculated Formulas (4) (5) (7), it can be observed that TESg, TESn and TESs can help construct a country's total carried environmental stress via the material flow indicators. Ecological footprint intensity indicators and ecological overshoot indicators.

  7. [Indications for micrograft hair transplantation].

    Science.gov (United States)

    Bouhanna, P

    2002-05-01

    Advances in treatment of androgenetic alopecia have led to the development of novel medical or surgical therapies adapted to the severity of hair loss and balding. Follicular units or tiny micro-graft hair transplants are a fundamental technical progress. This technique leads to the simple and painless permanent restoration of hair in male and female baldness. It provides the patient with a group of 1 to 3 hairs, emerging from a single orifice. The difference between androgenic receptors of occipital areas and those of other areas explains the permanent nature of the implanted hair growth. The degree of male or female androgenetic alopecia can be determined according to Hamilton's static classification or Ludwig's Classification, or it can be measured and monitored more accurately with Bouhanna's Dynamic Multifactorial Classification. The current indications for micro-graft transplantation are

  8. NRC performance indicator program

    International Nuclear Information System (INIS)

    Singh, R.N.

    1987-01-01

    The performance indicator development work of the US Nuclear Regulatory Commission (NRC) interoffice task group involved several major activities that included selection of candidate indicators for a trial program, data collection and review, validation of the trial indicators, display method development, interactions with the industry, and selection of an optimum set of indicators for the program. After evaluating 27 potential indicators against certain ideal attributes, the task group selected 17 for the trial program. The pertinent data for these indicators were then collected from 50 plants at 30 sites. The validation of the indicators consisted of two primary processes: logical validity and statistical analysis. The six indicators currently in the program are scrams, safety system actuations, significant events, safety system failures, forced outage rate, and equipment forced outages per 100 critical hours. A report containing data on the six performance indicators and some supplemental information is issued on a quarterly basis. The NRC staff is also working on refinements of existing indicators and development of additional indicators as directed by the commission

  9. CREDIT Performance Indicator Framework

    DEFF Research Database (Denmark)

    Frandsen, Anne Kathrine; Bertelsen, Niels Haldor; Haugbølle, Kim

    2010-01-01

    was a framework of indicators relevant in building and real estate and applicable in the Nordic and Baltic countries as well as a proposal for a set of key indicators. The study resulting in CREDIT Performance Indicator Framework has been based on 28 case studies of evaluation practises in the building and real...... estate sector each addressing three interlinked levels: building/ projects level, company or enterprise level and benchmarking system level. Additionally it has been based on dialogue with researchers and professional organisation, international research and standardisation work and national building...... regulations in the countries participating in CREDIT. The Performance Indicator Framework encompassed 187 indicators grouped in 7 main groups of indicators and 42 sub-groups. Based on the CREDIT case studies it was concluded that there neither is link between certain indicators and specific building types...

  10. Local adaptation in brown trout early life-history traits: implications for climate change adaptability

    DEFF Research Database (Denmark)

    Jensen, L.F.; Hansen, Michael Møller; Pertoldi, C.

    2008-01-01

      Knowledge of local adaptation and adaptive potential of natural populations is becoming increasingly relevant due to anthropogenic changes in the environment, such as climate change. The concern is that populations will be negatively affected by increasing temperatures without the capacity...... to adapt. Temperature-related adaptability in traits related to phenology and early life history are expected to be particularly important in salmonid fishes. We focused on the latter and investigated whether four populations of brown trout (Salmo trutta) are locally adapted in early life-history traits...... traits, indicating local adaptation. A temperature effect was observed for three traits. However, this effect varied among populations due to locally adapted reaction norms, corresponding to the temperature regimes experienced by the populations in their native environments. Additive genetic variance...

  11. Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.

    Science.gov (United States)

    Sadlecki, Pawel; Walentowicz, Pawel; Bodnar, Magdalena; Marszalek, Andrzej; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2017-05-01

    Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were

  12. Evolutionary force in confamiliar marine vertebrates of different temperature realms: adaptive trends in zoarcid fish transcriptomes

    Directory of Open Access Journals (Sweden)

    Windisch Heidrun Sigrid

    2012-10-01

    Full Text Available Abstract Background Studies of temperature-induced adaptation on the basis of genomic sequence data were mainly done in extremophiles. Although the general hypothesis of an increased molecular flexibility in the cold is widely accepted, the results of thermal adaptation are still difficult to detect at proteomic down to the genomic sequence level. Approaches towards a more detailed picture emerge with the advent of new sequencing technologies. Only small changes in primary protein structure have been shown to modify kinetic and thermal properties of enzymes, but likewise for interspecies comparisons a high genetic identity is still essential to specify common principles. The present study uses comprehensive transcriptomic sequence information to uncover general patterns of thermal adaptation on the RNA as well as protein primary structure. Results By comparing orthologous sequences of two closely related zoarcid fish inhabiting different latitudinal zones (Antarctica: Pachycara brachycephalum, temperate zone: Zoarces viviparus we were able to detect significant differences in the codon usage. In the cold-adapted species a lower GC content in the wobble position prevailed for preserved amino acids. We were able to estimate 40-60% coverage of the functions represented within the two compared zoarcid cDNA-libraries on the basis of a reference genome of the phylogenetically closely related fish Gasterosteus aculeatus. A distinct pattern of amino acid substitutions could be identified for the non-synonymous codon exchanges, with a remarkable surplus of serine and reduction of glutamic acid and asparagine for the Antarctic species. Conclusion Based on the differences between orthologous sequences from confamiliar species, distinguished mainly by the temperature regimes of their habitats, we hypothesize that temperature leaves a signature on the composition of biological macromolecules (RNA, proteins with implications for the transcription and

  13. Adapting to climate change

    Science.gov (United States)

    Constance I. Millar; Christopher W. Swanston; David L. Peterson

    2014-01-01

    Federal agencies have led the development of adaptation principles and tools in forest ecosystems over the past decade. Successful adaptation efforts generally require organizations to: (1) develop science-management partnerships, (2) provide education on climate change science, (3) provide a toolkit of methods and processes for vulnerability assessment and adaptation...

  14. Adaptation to climate change

    NARCIS (Netherlands)

    Carmin, J.; Tierney, K.; Chu, E.; Hunter, L.M.; Roberts, J.T.; Shi, L.; Dunlap, R.E.; Brulle, R.J.

    2015-01-01

    Climate change adaptation involves major global and societal challenges such as finding adequate and equitable adaptation funding and integrating adaptation and development programs. Current funding is insufficient. Debates between the Global North and South center on how best to allocate the

  15. A Holistic Management Architecture for Large-Scale Adaptive Networks

    National Research Council Canada - National Science Library

    Clement, Michael R

    2007-01-01

    This thesis extends the traditional notion of network management as an indicator of resource availability and utilization into a systemic model of resource requirements, capabilities, and adaptable...

  16. Climate Change Indicators

    Science.gov (United States)

    Presents information, charts and graphs showing measured climate changes across 40 indicators related to greenhouse gases, weather and climate, oceans, snow and ice, heath and society, and ecosystems.

  17. Chemical calcium indicators.

    Science.gov (United States)

    Paredes, R Madelaine; Etzler, Julie C; Watts, Lora Talley; Zheng, Wei; Lechleiter, James D

    2008-11-01

    Our understanding of the underlying mechanisms of Ca2+ signaling as well as our appreciation for its ubiquitous role in cellular processes has been rapidly advanced, in large part, due to the development of fluorescent Ca2+ indicators. In this chapter, we discuss some of the most common chemical Ca2+ indicators that are widely used for the investigation of intracellular Ca2+ signaling. Advantages, limitations and relevant procedures will be presented for each dye including their spectral qualities, dissociation constants, chemical forms, loading methods and equipment for optimal imaging. Chemical indicators now available allow for intracellular Ca2+ detection over a very large range (50 microM). High affinity indicators can be used to quantify Ca2+ levels in the cytosol while lower affinity indicators can be optimized for measuring Ca2+ in subcellular compartments with higher concentrations. Indicators can be classified into either single wavelength or ratiometric dyes. Both classes require specific lasers, filters, and/or detection methods that are dependent upon their spectral properties and both classes have advantages and limitations. Single wavelength indicators are generally very bright and optimal for Ca2+ detection when more than one fluorophore is being imaged. Ratiometric indicators can be calibrated very precisely and they minimize the most common problems associated with chemical Ca2+ indicators including uneven dye loading, leakage, photobleaching, and changes in cell volume. Recent technical advances that permit in vivo Ca2+ measurements will also be discussed.

  18. Creutzfeldt-Jakob Disease with a prion protein gene codon 180 mutation presenting asymmetric cortical high-intensity on magnetic resonance imaging.

    Science.gov (United States)

    Amano, Yuko; Kimura, Noriyuki; Hanaoka, Takuya; Aso, Yasuhiro; Hirano, Teruyuki; Murai, Hiroyuki; Satoh, Katsuya; Matsubara, Etsuro

    2015-01-01

    Here we report a genetically confirmed case of Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting atypical magnetic resonance imaging findings. The present case exhibited an acute onset and lateralized neurologic signs, and progressive cognitive impairment. No myoclonus or periodic synchronous discharges on electroencephalography were observed. Diffusion-weighted images revealed areas of high signal intensity in the right frontal and temporal cortices at onset that extended to the whole cortex and basal ganglia of the right cerebral hemisphere at 3 months. Although the cerebrospinal fluid (CSF) was initially negative for neuron specific enolase, tau protein, 14-3-3 protein, and abnormal prion protein, the CSF was positive for these brain-derived proteins at 3 months after onset.

  19. Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII

    Science.gov (United States)

    Lozier, Jay N; Kloos, Mark T; Merricks, Elizabeth P; Lemoine, Nathaly; Whitford, Margaret H; Raymer, Robin A; Bellinger, Dwight A; Nichols, Timothy C

    2016-01-01

    Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C→T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies (‘inhibitors’) to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. PMID:27780008

  20. High yield expression in a recombinant E. coli of a codon optimized chicken anemia virus capsid protein VP1 useful for vaccine development

    Directory of Open Access Journals (Sweden)

    You Bang-Jau

    2011-07-01

    Full Text Available Abstract Background Chicken anemia virus (CAV, the causative agent chicken anemia, is the only member of the genus Gyrovirus of the Circoviridae family. CAV is an immune suppressive virus and causes anemia, lymph organ atrophy and immunodeficiency. The production and biochemical characterization of VP1 protein and its use in a subunit vaccine or as part of a diagnostic kit would be useful to CAV infection prevention. Results Significantly increased expression of the recombinant full-length VP1 capsid protein from chicken anemia virus was demonstrated using an E. coli expression system. The VP1 gene was cloned into various different expression vectors and then these were expressed in a number of different E. coli strains. The expression of CAV VP1 in E. coli was significantly increased when VP1 was fused with GST protein rather than a His-tag. By optimizing the various rare amino acid codons within the N-terminus of the VP1 protein, the expression level of the VP1 protein in E. coli BL21(DE3-pLysS was further increased significantly. The highest protein expression level obtained was 17.5 g/L per liter of bacterial culture after induction with 0.1 mM IPTG for 2 h. After purification by GST affinity chromatography, the purified full-length VP1 protein produced in this way was demonstrated to have good antigenicity and was able to be recognized by CAV-positive chicken serum in an ELISA assay. Conclusions Purified recombinant VP1 protein with the gene's codons optimized in the N-terminal region has potential as chimeric protein that, when expressed in E. coli, may be useful in the future for the development of subunit vaccines and diagnostic tests.