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https://www.readbyqxmd.com/read/28642787/mutational-signatures-are-critical-for-proper-estimation-of-purifying-selection-pressures-in-cancer-somatic-mutation-data-when-using-the-dn-ds-metric
#1
Jimmy Van den Eynden, Erik Larsson
Large cancer genome sequencing initiatives have led to the identification of cancer driver genes based on signals of positive selection in somatic mutation data. Additionally, the identification of purifying (negative) selection has the potential to identify essential genes that may be of therapeutic interest. The most widely used way of quantifying selection pressures in protein-coding genes is the dN/dS metric, which compares non-synonymous to synonymous substitution rates. In this study, we examine whether and how this metric is influenced by the mutational processes that have been active during tumor evolution...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28642636/nucleotide-composition-determines-the-role-of-translational-efficiency-in-human-genes
#2
Binata Halder, Arup Kumar Malakar, Supriyo Chakraborty
The basic sequence features were analysed that influence gene expression via codon usage bias of the selected forty coding sequences of Homo sapiens in a simple prokaryotic model i.e. E. coli K-12 genome. The prime objective was to elucidate the interrelationships among tRNA gene copy numbers, synonymous codons, amino acids and translational efficiency using tRNA adaptation index. It was evident from RSCU scores and principal component analysis, that only those preferred codons were used by the isoacceptor tRNAs that had G and C base at their third codon position...
2017: Bioinformation
https://www.readbyqxmd.com/read/28637248/expression-and-comparison-of-codon-optimised-aspergillus-tubingensis-amylase-variants-in-saccharomyces-cerevisiae
#3
Rosemary A Cripwell, Shaunita H Rose, Willem H van Zyl
The expression of codon optimised genes is a popular genetic engineering approach for the production of industrially relevant proteins. This study investigates and compares the expression of codon optimised and codon adapted amylase variants. The Aspergillus tubingensis raw starch hydrolysing α-amylase (amyA) and glucoamylase (glaA) encoding genes were redesigned using synonymous codons and expressed in S. cerevisiae Y294. Codon optimisation to favour S. cerevisiae codon bias resulted in a decrease in extracellular enzyme activity of 72% (30...
June 15, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28630112/rapid-evolution-of-ovarian-biased-genes-in-the-yellow-fever-mosquito-aedes-aegypti
#4
Carrie A Whittle, Cassandra G Extavour
Males and females exhibit highly dimorphic phenotypes, particularly in their gonads, which is believed to be driven largely by differential gene expression. Typically, the protein sequences of genes upregulated in males, or male-biased genes, evolve rapidly as compared to female-biased and unbiased genes. To date, the specific study of gonad-biased genes remains uncommon in metazoans. Here, we identified and studied a total of 2,927, 2,013 and 4,449 coding-sequences (CDS) with ovary-biased, testis-biased and unbiased expression respectively in the yellow-fever mosquito Aedes aegypti The results showed that ovary-biased and unbiased CDS had higher nonsynonymous to synonymous substitution rates (dN/dS) and lower optimal codon usage (those codons that promote efficient translation) than testis-biased genes...
June 19, 2017: Genetics
https://www.readbyqxmd.com/read/28630001/host-influence-in-the-genomic-composition-of-flaviviruses-a-multivariate-approach
#5
Diego Simón, Alvaro Fajardo, Martín Sóñora, Adriana Delfraro, Héctor Musto
Flaviviruses present substantial differences in their host range and transmissibility. We studied the evolution of base composition, dinucleotide biases, codon usage and amino acid frequencies in the genus Flavivirus within a phylogenetic framework by principal components analysis. There is a mutual interplay between the evolutionary history of flaviviruses and their respective vectors and/or hosts. Hosts associated to distinct phylogenetic groups may be driving flaviviruses at different pace and through various sequence landscapes, as can be seen for viruses associated with Aedes or Culex spp...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28627970/genome-wide-codon-usage-profiling-of-ocular-infective-chlamydia-trachomatis-serovars-and-drug-target-identification
#6
Anupriya Sadhasivam, Umashankar Vetrivel
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 & 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...
June 19, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28625542/analysis-of-the-codon-usage-of-the-orf2-gene-of-feline-calicivirus
#7
Minghui Zang, Wanting He, Fanshu Du, Gongjian Wu, Bohao Wu, Zhenlei Zhou
Feline calicivirus (FCV) is a highly prevalent pathogen of the domestic cat that causes acute infections of the oral and upper respiratory tract. The E region of the ORF2 protein is responsible for the induction of virus-neutralizing antibodies, thus it is important to understand the codon usage of this gene. Here, analysed 90 coding sequences of ORF2 and show that it undergoes a low codon usage bias. In addition, although mutational bias is one of the factors shaping the codon usage bias of this gene, natural selection plays a more significant role...
June 16, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28625482/equalizing-the-information-amounts-of-protein-and-mrna-by-information-theory
#8
Y Adiguzel
Based on the Shannon's information communication theory, information amount of the entire length of a polymeric macromolecule can be calculated in bits through adding the entropies of each building block. Proteins, DNA and RNA are such macromolecules. When only the building blocks' variation is considered as the source of entropy, there is seemingly lower information in case of the protein if this approach is applied directly on a protein of specific size and the coding sequence size of the mRNA corresponding to the particular length of the protein...
June 15, 2017: Bio Systems
https://www.readbyqxmd.com/read/28623921/genome-wide-analysis-of-codon-usage-bias-in-bovine-coronavirus
#9
Matías Castells, Matías Victoria, Rodney Colina, Héctor Musto, Juan Cristina
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 codon usage and composition of BCoV...
June 17, 2017: Virology Journal
https://www.readbyqxmd.com/read/28623405/genome-dynamics-and-evolution-of-codon-usage-patterns-in-shrimp-viruses
#10
Anuj Tyagi, B T Naveen Kumar, Niraj K Singh
We analysed the genomes and codon usage patterns of seven small (DNA and RNA) shrimp viruses. Effective number of codon (ENC) values indicated moderate (35 < ENC < 50) codon usage bias in shrimp viruses. Correlation analysis between GC compositions at non-synonymous codon and synonymous codon positions (GC1, 2 and GC3) as well as GC3 versus ENC curves indicated varying influences of mutational pressure on codon usage. The presence of deoptimized codons and host-antagonistic codon usage trends in shrimp viruses suggested the adaptation of a slow replication strategy by these viruses to avoid host defences...
June 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28614378/comparative-analysis-of-virus-host-interactions-caused-by-a-virulent-and-an-attenuated-duck-hepatitis-a-virus-genotype-1
#11
Xumin Ou, Sai Mao, Jingyu Cao, Anchun Cheng, Mingshu Wang, Dekang Zhu, Shun Chen, Renyong Jia, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen
Because of their better immunogenicity and the improved protection they afford, live attenuated vaccines derived from serial passaging in an abnormal host are widely used to protect humans or animals from certain pathogens. Here, we used a virulent and a chicken embryo-attenuated duck hepatitis A virus genotype 1 to compare the different regulated immune responses induced by viruses with differing virulence. In this study, the attenuated strains had lower protein expression levels than the virulent strains as identified by immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28606821/analysis-of-synonymous-codon-usage-in-zika-virus
#12
Snawar Hussain, Sahibzada Tasleem Rasool
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...
June 9, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28603036/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
#13
Giovanni Franzo, Claudia Maria Tucciarone, Mattia Cecchinato, Michele Drigo
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)...
June 8, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28602802/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
#14
Weiheng Su, Xue Li, Meili Chen, Wenwen Dai, Shiyang Sun, Shuai Wang, Xin Sheng, Shixiang Sun, Chen Gao, Ali Hou, Yan Zhou, Bo Sun, Feng Gao, Jingfa Xiao, Zhewen Zhang, Chunlai Jiang
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...
June 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28593995/codon-bias-imposes-a-targetable-limitation-on-kras-driven-therapeutic-resistance
#15
Moiez Ali, Erin Kaltenbrun, Grace R Anderson, Sarah Jo Stephens, Sabrina Arena, Alberto Bardelli, Christopher M Counter, Kris C Wood
KRAS mutations drive resistance to targeted therapies, including EGFR inhibitors in colorectal cancer (CRC). Through genetic screens, we unexpectedly find that mutant HRAS, which is rarely found in CRC, is a stronger driver of resistance than mutant KRAS. This difference is ascribed to common codon bias in HRAS, which leads to much higher protein expression, and implies that the inherent poor expression of KRAS due to rare codons must be surmounted during drug resistance. In agreement, we demonstrate that primary resistance to cetuximab is dependent upon both KRAS mutational status and protein expression level, and acquired resistance is often associated with KRAS(Q61) mutations that function even when protein expression is low...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28587988/codon-usage-bias-and-its-influencing-factors-for-y-linked-genes-in-human
#16
Monisha Nath Choudhury, Arif Uddin, Supriyo Chakraborty
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)...
May 27, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28582582/codon-usage-regulates-protein-structure-and-function-by-affecting-translation-elongation-speed-in-drosophila-cells
#17
Fangzhou Zhao, Chien-Hung Yu, Yi Liu
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...
June 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28558053/novel-mrna-specific-effects-of-ribosome-drop-off-on-translation-rate-and-polysome-profile
#18
Pierre Bonnin, Norbert Kern, Neil T Young, Ian Stansfield, M Carmen Romano
The well established phenomenon of ribosome drop-off plays crucial roles in translational accuracy and nutrient starvation responses during protein translation. When cells are under stress conditions, such as amino acid starvation or aminoacyl-tRNA depletion due to a high level of recombinant protein expression, ribosome drop-off can substantially affect the efficiency of protein expression. Here we introduce a mathematical model that describes the effects of ribosome drop-off on the ribosome density along the mRNA and on the concomitant protein synthesis rate...
May 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28549175/selfing-in-haploid-plants-and-efficacy-of-selection-codon-usage-bias-in-the-model-moss-physcomitrella-patens
#19
Péter Szövényi, Kristian K Ullrich, Stefan A Rensing, Daniel Lang, Nico van Gessel, Hans K Stenøien, Elena Conti, Ralf Reski
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...
May 26, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28545477/optimizing-complex-phenotypes-through-model-guided-multiplex-genome-engineering
#20
Gleb Kuznetsov, Daniel B Goodman, Gabriel T Filsinger, Matthieu Landon, Nadin Rohland, John Aach, Marc J Lajoie, George M Church
We present a method for identifying genomic modifications that optimize a complex phenotype through multiplex genome engineering and predictive modeling. We apply our method to identify six single nucleotide mutations that recover 59% of the fitness defect exhibited by the 63-codon E. coli strain C321.∆A. By introducing targeted combinations of changes in multiplex we generate rich genotypic and phenotypic diversity and characterize clones using whole-genome sequencing and doubling time measurements. Regularized multivariate linear regression accurately quantifies individual allelic effects and overcomes bias from hitchhiking mutations and context-dependence of genome editing efficiency that would confound other strategies...
May 25, 2017: Genome Biology
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