scholarly journals Conserved codon adaptation in highly expressed genes is associated with higher regularity in mRNA secondary structures

2020 ◽  
Author(s):  
Mark G. Sterken ◽  
Ruud H.P. Wilbers ◽  
Pjotr Prins ◽  
Basten L. Snoek ◽  
George M. Giambasu ◽  
...  
Keyword(s):  
Codon Usage ◽  
Developmental Stages ◽  
Synonymous Codon ◽  
Expression Profiles ◽  
Secondary Structures ◽  
Relative Increase ◽  
Synonymous Codon Usage ◽  
Translation Efficiency ◽  
Highly Expressed Genes ◽  
Higher Regularity

ABSTRACTThe redundancy of the genetic code allows for a regulatory layer to optimize protein synthesis by modulating translation and degradation of mRNAs. Patterns in synonymous codon usage in highly expressed genes have been studied in many species, but scarcely in conjunction with mRNA secondary structure. Here, we analyzed over 2,000 expression profiles covering a range of strains, treatments, and developmental stages of five model species (Escherichia coli, Arabidopsis thaliana, Saccharomyces cerevisiae, Caenorhabditis elegans, and Mus musculus). By comparative analyses of genes constitutively expressed at high and low levels, we revealed a conserved shift in codon usage and predicted mRNA secondary structures. Highly abundant transcripts and proteins, as well as high protein per transcript ratios, were consistently associated with less variable and shorter stretches of weak mRNA secondary structures (loops). Genome-wide recoding showed that codons with the highest relative increase in highly expressed genes, often C-ending and not necessarily the most frequent, enhanced formation of uniform loop sizes. Our results point at a general selective force contributing to the optimal expression of abundant proteins as less variable secondary structures promote regular ribosome trafficking with less detrimental collisions, thereby leading to an increase in mRNA stability and a higher translation efficiency.

scholarly journals Synonymous Codon Usage Analysis of Thirty Two Mycobacteriophage Genomes

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Sameer Hassan ◽  
Vasantha Mahalingam ◽  
Vanaja Kumar
Keyword(s):  
Codon Usage ◽  
Synonymous Codon ◽  
Nucleotide Composition ◽  
Synonymous Codon Usage ◽  
Compositional Bias ◽  
Trna Genes ◽  
Translation Efficiency ◽  
Multivariate Statistical ◽  
Strong Negative Correlation ◽  
Highly Expressed Genes

Synonymous codon usage of protein coding genes of thirty two completely sequenced mycobacteriophage genomes was studied using multivariate statistical analysis. One of the major factors influencing codon usage is identified to be compositional bias. Codons ending with either C or G are preferred in highly expressed genes among which C ending codons are highly preferred over G ending codons. A strong negative correlation between effective number of codons (Nc) and GC3s content was also observed, showing that the codon usage was effected by gene nucleotide composition. Translational selection is also identified to play a role in shaping the codon usage operative at the level of translational accuracy. High level of heterogeneity is seen among and between the genomes. Length of genes is also identified to influence the codon usage in 11 out of 32 phage genomes. Mycobacteriophage Cooper is identified to be the highly biased genome with better translation efficiency comparing well with the host specific tRNA genes.

scholarly journals The selection-mutation-drift theory of synonymous codon usage.

Genetics ◽  
1991 ◽  
Vol 129 (3) ◽  
pp. 897-907 ◽  
Author(s):  
M Bulmer
Keyword(s):  
Codon Usage ◽  
Genetic Model ◽  
Synonymous Codon ◽  
Growth Yield ◽  
Synonymous Codon Usage ◽  
Synonymous Codons ◽  
Drift Theory ◽  
Highly Expressed Genes ◽  
Unicellular Organisms ◽  
Selection For

Abstract It is argued that the bias in synonymous codon usage observed in unicellular organisms is due to a balance between the forces of selection and mutation in a finite population, with greater bias in highly expressed genes reflecting stronger selection for efficiency of translation. A population genetic model is developed taking into account population size and selective differences between synonymous codons. A biochemical model is then developed to predict the magnitude of selective differences between synonymous codons in unicellular organisms in which growth rate (or possibly growth yield) can be equated with fitness. Selection can arise from differences in either the speed or the accuracy of translation. A model for the effect of speed of translation on fitness is considered in detail, a similar model for accuracy more briefly. The model is successful in predicting a difference in the degree of bias at the beginning than in the rest of the gene under some circumstances, as observed in Escherichia coli, but grossly overestimates the amount of bias expected. Possible reasons for this discrepancy are discussed.

scholarly journals Recombination, meiotic expression and human codon usage

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Fanny Pouyet ◽  
Dominique Mouchiroud ◽  
Laurent Duret ◽  
Marie Sémon
Keyword(s):  
Codon Usage ◽  
Large Scale ◽  
Synonymous Codon ◽  
Gc Content ◽  
Synonymous Codon Usage ◽  
Translation Efficiency ◽  
Functional Categories ◽  
Human Genes ◽  
Biased Gene Conversion ◽  
Mammalian Genomes

Synonymous codon usage (SCU) varies widely among human genes. In particular, genes involved in different functional categories display a distinct codon usage, which was interpreted as evidence that SCU is adaptively constrained to optimize translation efficiency in distinct cellular states. We demonstrate here that SCU is not driven by constraints on tRNA abundance, but by large-scale variation in GC-content, caused by meiotic recombination, via the non-adaptive process of GC-biased gene conversion (gBGC). Expression in meiotic cells is associated with a strong decrease in recombination within genes. Differences in SCU among functional categories reflect differences in levels of meiotic transcription, which is linked to variation in recombination and therefore in gBGC. Overall, the gBGC model explains 70% of the variance in SCU among genes. We argue that the strong heterogeneity of SCU induced by gBGC in mammalian genomes precludes any optimization of the tRNA pool to the demand in codon usage.

Codon Usage Bias Covaries With Expression Breadth and the Rate of Synonymous Evolution in Humans, but This Is Not Evidence for Selection

Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 1191-1199
Author(s):  
Araxi O Urrutia ◽  
Laurence D Hurst
Keyword(s):  
Codon Usage ◽  
Codon Bias ◽  
Synonymous Codon ◽  
Nucleotide Composition ◽  
Synonymous Codon Usage ◽  
Synonymous Substitutions ◽  
Numerous Species ◽  
Nucleotide Content ◽  
Expression Breadth ◽  
Human Genes

Abstract In numerous species, from bacteria to Drosophila, evidence suggests that selection acts even on synonymous codon usage: codon bias is greater in more abundantly expressed genes, the rate of synonymous evolution is lower in genes with greater codon bias, and there is consistency between genes in the same species in which codons are preferred. In contrast, in mammals, while nonequal use of alternative codons is observed, the bias is attributed to the background variance in nucleotide concentrations, reflected in the similar nucleotide composition of flanking noncoding and exonic third sites. However, a systematic examination of the covariants of codon usage controlling for background nucleotide content has yet to be performed. Here we present a new method to measure codon bias that corrects for background nucleotide content and apply this to 2396 human genes. Nearly all (99%) exhibit a higher amount of codon bias than expected by chance. The patterns associated with selectively driven codon bias are weakly recovered: Broadly expressed genes have a higher level of bias than do tissue-specific genes, the bias is higher for genes with lower rates of synonymous substitutions, and certain codons are repeatedly preferred. However, while these patterns are suggestive, the first two patterns appear to be methodological artifacts. The last pattern reflects in part biases in usage of nucleotide pairs. We conclude that we find no evidence for selection on codon usage in humans.

scholarly journals Effect of genome composition and codon bias on infectious bronchitis virus evolution and adaptation to target tissues

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Giovanni Franzo ◽  
Claudia Maria Tucciarone ◽  
Matteo Legnardi ◽  
Mattia Cecchinato
Keyword(s):  
Codon Usage ◽  
Codon Bias ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Accessory Proteins ◽  
Effective Number ◽  
Genome Composition ◽  
Infectious Bronchitis ◽  
Selective Forces ◽  
Effective Number Of Codons

Abstract Background Infectious bronchitis virus (IBV) is one of the most relevant viruses affecting the poultry industry, and several studies have investigated the factors involved in its biological cycle and evolution. However, very few of those studies focused on the effect of genome composition and the codon bias of different IBV proteins, despite the remarkable increase in available complete genomes. In the present study, all IBV complete genomes were downloaded (n = 383), and several statistics representative of genome composition and codon bias were calculated for each protein-coding sequence, including but not limited to, the nucleotide odds ratio, relative synonymous codon usage and effective number of codons. Additionally, viral codon usage was compared to host codon usage based on a collection of highly expressed genes in IBV target and nontarget tissues. Results The results obtained demonstrated a significant difference among structural, non-structural and accessory proteins, especially regarding dinucleotide composition, which appears under strong selective forces. In particular, some dinucleotide pairs, such as CpG, a probable target of the host innate immune response, are underrepresented in genes coding for pp1a, pp1ab, S and N. Although genome composition and dinucleotide bias appear to affect codon usage, additional selective forces may act directly on codon bias. Variability in relative synonymous codon usage and effective number of codons was found for different proteins, with structural proteins and polyproteins being more adapted to the codon bias of host target tissues. In contrast, accessory proteins had a more biased codon usage (i.e., lower number of preferred codons), which might contribute to the regulation of their expression level and timing throughout the cell cycle. Conclusions The present study confirms the existence of selective forces acting directly on the genome and not only indirectly through phenotype selection. This evidence might help understanding IBV biology and in developing attenuated strains without affecting the protein phenotype and therefore immunogenicity.

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