scholarly journals Accounting for programmed ribosomal frameshifting in the computation of codon

2018 ◽  
Author(s):  
Victor Garcia ◽  
Stefan Zoller ◽  
Maria Anisimova
Keyword(s):  
Protein Expression ◽  
Translational Efficiency ◽  
Translation Efficiency ◽  
Ribosomal Frameshifting ◽  
Synonymous Mutations ◽  
Synonymous Codons ◽  
Distinct Frequency ◽  
Selection For ◽  
Accuracy Constraints ◽  
Genetic Fitness

Experimental evidence shows that synonymous mutations can have important consequences on genetic fitness. Many organisms display codon usage bias (CUB), where synonymous codons that are translated into the same amino acid appear with distinct frequency. CUB is thought to arise from selection for translational efficiency and accuracy, termed the translational efficiency hypothesis (TEH). Indeed, CUB indices correlate with protein expression levels, which is widely interpreted as evidence for translational selection. However, these tests neglect −1 programmed ribosomal frameshifting (−1 PRF), an important translational disruption effect found across all organisms of the tree of life. Genes that contain −1 PRF signals should cost more to express than genes without. Thus, CUB indices that do not consider −1 PRF may overestimate genes’ true adaptation to translational efficiency and accuracy constraints. Here, we first investigate whether −1 PRF signals do indeed carry such translational cost. We then propose two corrections for CUB indices for genes containing −1 PRF signals. We retest the TEH under these corrections. We find that the correlation between corrected CUB index and protein expression remains intact for most levels of uniform −1 PRF efficiencies, and tends to increase when these efficiencies decline with protein expression. We conclude that the TEH is strengthened and that −1 PRF events constitute a promising and useful tool to examine the relationships between CUB and selection for translation efficiency and accuracy.

In Vivo Introduction of Unpreferred Synonymous Codons Into the Drosophila Adh Gene Results in Reduced Levels of ADH Protein

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 239-243 ◽  
Author(s):  
David B Carlini ◽  
Wolfgang Stephan
Keyword(s):  
Natural Selection ◽  
Codon Bias ◽  
Protein Production ◽  
Empirical Relationship ◽  
Abundant Species ◽  
Translational Efficiency ◽  
Synonymous Mutations ◽  
Synonymous Codons ◽  
Synonymous Sites

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

Translational regulation of human beta interferon mRNA: association of the 3' AU-rich sequence with the poly(A) tail reduces translation efficiency in vitro

1993 ◽  
Vol 13 (6) ◽  
pp. 3487-3493
Author(s):  
G Grafi ◽  
I Sela ◽  
G Galili
Keyword(s):  
Translational Regulation ◽  
Binding Activity ◽  
Rnase H ◽  
Translational Efficiency ◽  
Translation Efficiency ◽  
Protection Assay ◽  
Rich Region ◽  
Reticulocyte Lysate ◽  
Rna Probe

The 3' AU-rich region of human beta-1 interferon (hu-IFN beta) mRNA was found to act as a translational inhibitory element. The translational regulation of this 3' AU-rich sequence and the effect of its association with the poly(A) tail were studied in cell-free rabbit reticulocyte lysate. A poly(A)-rich hu-IFN beta mRNA (110 A residues) served as an inefficient template for protein synthesis. However, translational efficiency was considerably improved when the poly(A) tract was shortened (11 A residues) or when the 3' AU-rich sequence was deleted, indicating that interaction between these two regions was responsible for the reduced translation of the poly(A)-rich hu-IFN beta mRNA. Differences in translational efficiency of the various hu-IFN beta mRNAs correlated well with their polysomal distribution. The poly(A)-rich hu-IFN beta mRNA failed to form large polysomes, while its counterpart bearing a short poly(A) tail was recruited more efficiently into large polysomes. The AU-rich sequence-binding activity was reduced when the RNA probe contained both the 3' AU-rich sequence and long poly(A) tail, supporting a physical association between these two regions. Further evidence for this interaction was achieved by RNase H protection assay. We suggest that the 3' AU-rich sequence may regulate the translation of hu-IFN beta mRNA by interacting with the poly(A) tail.

scholarly journals Codon usage bias creates a ramp of hydrogen bonding at the 5′-end in prokaryotic ORFeomes

2019 ◽  
Author(s):  
Juan C. Villada ◽  
Maria F. Duran ◽  
Patrick K. H. Lee
Keyword(s):  
Hydrogen Bonding ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Translation Efficiency ◽  
Molecular Processes ◽  
Molecular Feature ◽  
Web Based ◽  
Synonymous Codons ◽  
Double Stranded Dna ◽  
Codon Positions

Codon usage bias exerts control over a wide variety of molecular processes. The positioning of synonymous codons within coding sequences (CDSs) dictates protein expression by mechanisms such as local translation efficiency, mRNA Gibbs free energy, and protein co-translational folding. In this work, we explore how codon variants affect the position-dependent content of hydrogen bonding, which in turn influences energy requirements for unwinding double-stranded DNA. By analyzing over 14,000 bacterial, archaeal, and fungal ORFeomes, we found that Bacteria and Archaea exhibit an exponential ramp of hydrogen bonding at the 5′-end of CDSs, while a similar ramp was not found in Fungi. The ramp develops within the first 20 codon positions in prokaryotes, eventually reaching a steady carrying capacity of hydrogen bonding that does not differ from Fungi. Selection against uniformity tests proved that selection acts against synonymous codons with high content of hydrogen bonding at the 5′-end of prokaryotic ORFeomes. Overall, this study provides novel insights into the molecular feature of hydrogen bonding that is governed by the genetic code at the 5′-end of CDSs. A web-based application to analyze the position-dependent hydrogen bonding of ORFeomes has been developed and is publicly available (https://juanvillada.shinyapps.io/hbonds/).

scholarly journals Polyandry enhances offspring survival in an infanticidal species

2009 ◽  
Vol 6 (1) ◽  
pp. 24-26 ◽  
Author(s):  
Ines Klemme ◽  
Hannu Ylönen
Keyword(s):  
Mating Systems ◽  
Multiple Mating ◽  
Empirical Test ◽  
Myodes Glareolus ◽  
Offspring Survival ◽  
Bank Voles ◽  
Female Counterstrategy ◽  
Fitness Benefits ◽  
Selection For ◽  
Genetic Fitness

The adaptive significance of polyandry is an intensely debated subject in sexual selection. For species with male infanticidal behaviour, it has been hypothesized that polyandry evolved as female counterstrategy to offspring loss: by mating with multiple males, females may conceal paternity and so prevent males from killing putative offspring. Here we present, to our knowledge, the first empirical test of this hypothesis in a combined laboratory and field study, and show that multiple mating seems to reduce the risk of infanticide in female bank voles Myodes glareolus . Our findings thus indicate that females of species with non-resource based mating systems, in which males provide nothing but sperm, but commit infanticide, can gain non-genetic fitness benefits from polyandry.

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

2015 ◽  
Vol 13 (02) ◽  
pp. 1550002
Author(s):  
Mohammad-Hadi Foroughmand-Araabi ◽  
Bahram Goliaei ◽  
Kasra Alishahi ◽  
Mehdi Sadeghi ◽  
Sama Goliaei
Keyword(s):  
Gene Regulation ◽  
Codon Usage ◽  
Protein Sequence ◽  
Multinomial Logistic Regression ◽  
Translation Efficiency ◽  
Translation Rate ◽  
Protein Levels ◽  
Synonymous Codons ◽  
First Time

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.

scholarly journals Codon usage of highly expressed genes affects proteome-wide translation efficiency

2018 ◽  
Vol 115 (21) ◽  
pp. E4940-E4949 ◽  
Author(s):  
Idan Frumkin ◽  
Marc J. Lajoie ◽  
Christopher J. Gregg ◽  
Gil Hornung ◽  
George M. Church ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Protein Translation ◽  
Translation Efficiency ◽  
Synonymous Codons ◽  
Codon Composition ◽  
Theoretical Predictions ◽  
Highly Expressed Genes

Although the genetic code is redundant, synonymous codons for the same amino acid are not used with equal frequencies in genomes, a phenomenon termed “codon usage bias.” Previous studies have demonstrated that synonymous changes in a coding sequence can exert significantciseffects on the gene’s expression level. However, whether the codon composition of a gene can also affect the translation efficiency of other genes has not been thoroughly explored. To study how codon usage bias influences the cellular economy of translation, we massively converted abundant codons to their rare synonymous counterpart in several highly expressed genes inEscherichia coli. This perturbation reduces both the cellular fitness and the translation efficiency of genes that have high initiation rates and are naturally enriched with the manipulated codon, in agreement with theoretical predictions. Interestingly, we could alleviate the observed phenotypes by increasing the supply of the tRNA for the highly demanded codon, thus demonstrating that the codon usage of highly expressed genes was selected in evolution to maintain the efficiency of global protein translation.

scholarly journals Parsing the synonymous mutations in the maize genome: isoaccepting mutations are more advantageous in regions with codon co-occurrence bias

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Duan Chu ◽  
Lai Wei
Keyword(s):  
Amino Acids ◽  
Natural Selection ◽  
Codon Bias ◽  
Synonymous Codon ◽  
Translation Efficiency ◽  
Maize Genome ◽  
Rna Seq ◽  
Synonymous Mutations ◽  
Coding Regions ◽  
The Relationship

Abstract Background Synonymous mutations do not change amino acids but do sometimes change the tRNAs (anticodons) that decode a particular codon. An isoaccepting codon is a synonymous codon that shares the same tRNA. If a mutated codon could base pair with the same anticodon as the original, the mutation is termed an isoaccepting mutation. An interesting but less-studied type of codon bias is codon co-occurrence bias. There is a trend to cluster the isoaccepting codons in the genome. The proposed advantage of codon co-occurrence bias is that the tRNA released from the ribosome E site could be quickly recharged and subsequently decode the following isoaccepting codons. This advantage would enhance translation efficiency. In plant species, whether there are signals of positive selection on isoaccepting mutations in the codon co-occurred regions has not been studied. Results We termed polymorphic mutations in coding regions using publicly available RNA-seq data in maize (Zea mays). Next, we classified all synonymous mutations into three categories according to the context, i.e., the relationship between the focal codon and the previous codon, as follows: isoaccepting, nonisoaccepting and nonsynonymous. We observed higher fractions of isoaccepting mutations in the isoaccepting context. If we looked at the minor allele frequency (MAF) spectrum, the isoaccepting mutations have a higher MAF in the isoaccepting context than that in other regions, and accordingly, the nonisoaccepting mutations have a higher MAF in the nonisoaccepting context. Conclusion Our results indicate that in regions with codon co-occurrence bias, natural selection maintains this pattern by suppressing the nonisoaccepting mutations. However, if the consecutive codons are nonisoaccepting, mutations tend to switch these codons to become isoaccepting. Our study demonstrates that the codon co-occurrence bias in the maize genome is selectively maintained by natural selection and that the advantage of this trend could potentially be the rapid recharging and reuse of tRNAs to increase translation efficiency.

scholarly journals Widespread selection for extremely high and low levels of secondary structure in coding sequences across all domains of life

Open Biology ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 190020 ◽  
Author(s):  
Daniel Gebert ◽  
Julia Jehn ◽  
David Rosenkranz
Keyword(s):  
Secondary Structure ◽  
Gc Content ◽  
Secondary Structures ◽  
Coding Sequences ◽  
Rna Secondary Structures ◽  
Synonymous Mutations ◽  
Codon Composition ◽  
Domains Of Life ◽  
Low Levels ◽  
Selection For

Codon composition, GC content and local RNA secondary structures can have a profound effect on gene expression, and mutations affecting these parameters, even though they do not alter the protein sequence, are not neutral in terms of selection. Although evidence exists that, in some cases, selection favours more stable RNA secondary structures, we currently lack a concrete idea of how many genes are affected within a species, and whether this is a universal phenomenon in nature. We searched for signs of structural selection in a global manner, analysing a set of 1 million coding sequences from 73 species representing all domains of life, as well as viruses, by means of our newly developed software PACKEIS. We show that codon composition and amino acid identity are main determinants of RNA secondary structure. In addition, we show that the arrangement of synonymous codons within coding sequences is non-random, yielding extremely high, but also extremely low, RNA structuredness significantly more often than expected by chance. Taken together, we demonstrate that selection for high and low levels of secondary structure is a widespread phenomenon. Our results provide another line of evidence that synonymous mutations are less neutral than commonly thought, which is of importance for many evolutionary models.

scholarly journals RiboToolkit: an integrated platform for analysis and annotation of ribosome profiling data to decode mRNA translation at codon resolution

2020 ◽  
Vol 48 (W1) ◽  
pp. W218-W229 ◽  
Author(s):  
Qi Liu ◽  
Tanya Shvarts ◽  
Piotr Sliz ◽  
Richard I Gregory
Keyword(s):  
Mrna Translation ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Translational Efficiency ◽  
Translation Efficiency ◽  
Sequencing Data ◽  
Experimental Conditions ◽  
Web Based ◽  
Rna Translation ◽  
Web Interfaces

Abstract Ribosome profiling (Ribo-seq) is a powerful technology for globally monitoring RNA translation; ranging from codon occupancy profiling, identification of actively translated open reading frames (ORFs), to the quantification of translational efficiency under various physiological or experimental conditions. However, analyzing and decoding translation information from Ribo-seq data is not trivial. Although there are many existing tools to analyze Ribo-seq data, most of these tools are designed for specific or limited functionalities and an easy-to-use integrated tool to analyze Ribo-seq data is lacking. Fortunately, the small size (26–34 nt) of ribosome protected fragments (RPFs) in Ribo-seq and the relatively small amount of sequencing data greatly facilitates the development of such a web platform, which is easy to manipulate for users with or without bioinformatic expertise. Thus, we developed RiboToolkit (http://rnabioinfor.tch.harvard.edu/RiboToolkit), a convenient, freely available, web-based service to centralize Ribo-seq data analyses, including data cleaning and quality evaluation, expression analysis based on RPFs, codon occupancy, translation efficiency analysis, differential translation analysis, functional annotation, translation metagene analysis, and identification of actively translated ORFs. Besides, easy-to-use web interfaces were developed to facilitate data analysis and intuitively visualize results. Thus, RiboToolkit will greatly facilitate the study of mRNA translation based on ribosome profiling.

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