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

In this paper we introduce a new notion of realizability for intuitionistic arithmetic in all finite types. The notion seems to us to capture some of the intuition underlying both the recursive realizability of Kjeene [5] and the semantics of Kripke [7]. After some preliminaries of a syntactic and recursion-theoretic character in §1, we motivate and define our notion of realizability in §2. In §3 we prove a soundness theorem, and in §4 we apply that theorem to obtain new information about provability in some extensions of intuitionistic arithmetic in all finite types. In §5 we consider a special case of our general notion and prove a kind of reflection theorem for it. Finally, in §6, we consider a formalized version of our realizability notion and use it to give a new proof of the conservative extension theorem discussed in Goodman and Myhill [4] and proved in our [3]. (Apparently, a form of this result is also proved in Mine [13]. We have not seen this paper, but are relying on [12].) As a corollary, we obtain the following somewhat strengthened result: Let Σ be any extension of first-order intuitionistic arithmetic (HA) formalized in the language of HA. Let Σω be the theory obtained from Σ by adding functionals of finite type with intuitionistic logic, intensional identity, and axioms of choice and dependent choice at all types. Then Σω is a conservative extension of Σ. An interesting example of this theorem is obtained by taking Σ to be classical first-order arithmetic.

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Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway

Scientific Reports ◽

10.1038/s41598-020-78453-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jackson Peterson ◽

Siqi Li ◽

Erin Kaltenbrun ◽

Ozgun Erdogan ◽

Christopher M. Counter

Keyword(s):

Amino Acids ◽

Protein Kinase ◽

Mapk Pathway ◽

Mitogen Activated Protein Kinase ◽

Rare Codons ◽

Synonymous Codons ◽

Multiple Components ◽

Human Genes ◽

Regulatory Module ◽

Mitogen Activated Protein

AbstractThe ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched in rare codons are typically associated with poor translation, but in certain settings can be robustly expressed, suggestive of codon-dependent regulation. Given this, we screened a gain-of-function library for human genes that increase the expression of a GFPrare reporter encoded by rare codons. This screen identified multiple components of the mitogen activated protein kinase (MAPK) pathway enhancing GFPrare expression. This effect was reversed with inhibitors of this pathway and confirmed to be both codon-dependent and occur with ectopic transcripts naturally coded with rare codons. Finally, this effect was associated, at least in part, with enhanced translation. We thus identify a potential regulatory module that takes advantage of the redundancy in the genetic code to modulate protein expression.

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The effect of expression levels on codon usage inPlasmodium falciparum

Parasitology ◽

10.1017/s0031182003004517 ◽

2004 ◽

Vol 128 (3) ◽

pp. 245-251 ◽

Cited By ~ 26

Author(s):

L. PEIXOTO ◽

V. FERNÁNDEZ ◽

H. MUSTO

Keyword(s):

Amino Acids ◽

Plasmodium Falciparum ◽

Natural Selection ◽

Codon Usage ◽

Complete Sequence ◽

Expression Data ◽

Expression Levels ◽

Synonymous Codons ◽

Translational Selection ◽

Highly Expressed Genes

The usage of alternative synonymous codons in the completely sequenced, extremely A+T-rich parasitePlasmodium falciparumwas studied. Confirming previous studies obtained with less than 3% of the total genes recently described, we found that A- and U-ending triplets predominate but translational selection increases the frequency of a subset of codons in highly expressed genes. However, some new results come from the analysis of the complete sequence. First, there is more variation in GC3 than previously described; second, the effect of natural selection acting at the level of translation has been analysed with real expression data at 4 different stages and third, we found that highly expressed proteins increment the frequency of energetically less expensive amino acids. The implications of these results are discussed.

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Models of nearly neutral mutations with particular implications for nonrandom usage of synonymous codons

Journal of Molecular Evolution ◽

10.1007/bf02134132 ◽

1987 ◽

Vol 24 (4) ◽

pp. 337-345 ◽

Cited By ~ 137

Author(s):

Wen-Hsiung Li

Keyword(s):

Synonymous Codons ◽

Nearly Neutral Mutations ◽

Neutral Mutations

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Intrastrand parity rules of DNA base composition and usage biases of synonymous codons

Journal of Molecular Evolution ◽

10.1007/bf02198860 ◽

1996 ◽

Vol 42 (2) ◽

pp. 323-323 ◽

Cited By ~ 4

Author(s):

Noboru Sueoka

Keyword(s):

Base Composition ◽

Dna Base Composition ◽

Synonymous Codons ◽

Dna Base

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Presyncodon, a Web Server for Gene Design with the Evolutionary Information of the Expression Hosts

International Journal of Molecular Sciences ◽

10.3390/ijms19123872 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3872 ◽

Cited By ~ 2

Author(s):

Jian Tian ◽

Qingbin Li ◽

Xiaoyu Chu ◽

Ningfeng Wu

Keyword(s):

High Frequency ◽

Synonymous Codon ◽

Low Frequency ◽

Synonymous Codon Usage ◽

Codon Usage Pattern ◽

Evolutionary Information ◽

Specific Expression ◽

Synonymous Codons ◽

New Genes ◽

And Function

In the natural host, most of the synonymous codons of a gene have been evolutionarily selected and related to protein expression and function. However, for the design of a new gene, most of the existing codon optimization tools select the high-frequency-usage codons and neglect the contribution of the low-frequency-usage codons (rare codons) to the expression of the target gene in the host. In this study, we developed the method Presyncodon, available in a web version, to predict the gene code from a protein sequence, using built-in evolutionary information on a specific expression host. The synonymous codon-usage pattern of a peptide was studied from three genomic datasets (Escherichia coli, Bacillus subtilis, and Saccharomyces cerevisiae). Machine-learning models were constructed to predict a selection of synonymous codons (low- or high-frequency-usage codon) in a gene. This method could be easily and efficiently used to design new genes from protein sequences for optimal expression in three expression hosts (E. coli, B. subtilis, and S. cerevisiae). Presyncodon is free to academic and noncommercial users; accessible at http://www.mobioinfor.cn/presyncodon_www/index.html.

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MODIFIED BAR RECURSION AND CLASSICAL DEPENDENT CHOICE

Logic Colloquium '01 ◽

10.1201/9781439865736-3 ◽

2005 ◽

pp. 89-107

Author(s):

ULRICH BERGER ◽

PAULO OLIVA

Keyword(s):

Dependent Choice

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

10.1101/811612 ◽

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/).

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Analysis of computational codon usage models and their association with translationally slow codons

10.1101/2020.03.26.010488 ◽

2020 ◽

Author(s):

Gabriel Wright ◽

Anabel Rodriguez ◽

Jun Li ◽

Patricia L. Clark ◽

Tijana Milenković ◽

...

Keyword(s):

Codon Usage ◽

Computational Models ◽

Selective Pressure ◽

Synonymous Codon ◽

Ground Truth ◽

Protein Translation ◽

Weak Correlation ◽

Experimental Conditions ◽

Synonymous Codons ◽

Genome Wide

AbstractImproved computational modeling of protein translation rates, including better prediction of where translational slowdowns along an mRNA sequence may occur, is critical for understanding co-translational folding. Because codons within a synonymous codon group are translated at different rates, many computational translation models rely on analyzing synonymous codons. Some models rely on genome-wide codon usage bias (CUB), believing that globally rare and common codons are the most informative of slow and fast translation, respectively. Others use the CUB observed only in highly expressed genes, which should be under selective pressure to be translated efficiently (and whose CUB may therefore be more indicative of translation rates). No prior work has analyzed these models for their ability to predict translational slowdowns. Here, we evaluate five models for their association with slowly translated positions as denoted by two independent ribosome footprint (RFP) count experiments from S. cerevisiae, because RFP data is often considered as a “ground truth” for translation rates across mRNA sequences. We show that all five considered models strongly associate with the RFP data and therefore have potential for estimating translational slowdowns. However, we also show that there is a weak correlation between RFP counts for the same genes originating from independent experiments, even when their experimental conditions are similar. This raises concerns about the efficacy of using current RFP experimental data for estimating translation rates and highlights a potential advantage of using computational models to understand translation rates instead.

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