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

Genetics ◽  
1991 ◽  
Vol 129 (3) ◽  
pp. 897-907 ◽  
Author(s):  
M Bulmer

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.

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Sameer Hassan ◽  
Vasantha Mahalingam ◽  
Vanaja Kumar

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.


2013 ◽  
Vol 641-642 ◽  
pp. 693-700
Author(s):  
Ling Jie Zuo ◽  
An Chun Cheng ◽  
Ming Shu Wang

In this study, we calculated the codon usage bias in DPV CHv UL1 gene and performed a comparative analysis of synonymous codon patterns in UL1 of DPV CHv strain and other 19 reference herpesviruses. The results revealed that the synonymous codons with A and T at the third codon positon have widely usage in the codon of UL1 gene of DPV CHv. G + C compositional constraint was the main factor that determined the codon usage bias in UL1 gene. In addition, the codon usage bias of DPV CHv UL1 gene was compared with those of E. coli, yeast and human. There are 25 codons showing distinct usage differences between DPV and E. coli, 26 codons between DPV and yeast, and 21 codons between DPV and human. Therefore, the Human expression system is more suitable for heterologous expression of the DPV UL1 gene.


2013 ◽  
Vol 641-642 ◽  
pp. 654-665
Author(s):  
Si Si Yang ◽  
De Kang Zhu ◽  
Xiao Jia Wang ◽  
An Chun Cheng ◽  
Ming Shu Wang

The analysis on codon usage bias of Riemerella anatipestifer (RA) RagB/SusD gene (GenBank accession No. NC_017045.1) may improve our understanding of the evolution and pathogenesis of RA and provide a basis for understanding the relevant mechanism for biased usage of synonymous codons and for selecting appropriate expression systems to improve the expression of target genes. In this study, the synonymous codon usage in the RagB/SusD gene of RA and 19 reference bacteroidetes have been investigated. The results showed that codon usage bias in the RagB/SusD gene was strong bias towards the synonymous codons with A and T at the third codon position. A high level of diversity in codon usage bias existed, and the effective number of codons used in a gene plot revealed that the genetic heterogeneity in RagB/SusD gene of bacteroidetes was constrained by the G + C content. The codon adaptation index (CAI), effective number of codons (ENC), and GC3S values indicated synonymous codon usage bias in the RagB/SusD gene of bacteroidetes, and this synonymous bias was correlated with host evolution. The phylogentic analysis suggested that RagB/SusD was evolutionarily closer to Ornithobacterium rhinotracheale and that there was no significant deviation in codon usage in different bacteroidetes. There are 25 codons showing distinct usage differences between RA RagB/SusD and E. coli, 30 between RA RagB/SusD and Homo sapiens, 26 codons between RA RagB/SusD and yeast. Therefore the yeast and E. coli expression system may be suitable for the expression of RA RagB/SusD gene if some codons could be optimized.


2020 ◽  
Author(s):  
Mark G. Sterken ◽  
Ruud H.P. Wilbers ◽  
Pjotr Prins ◽  
Basten L. Snoek ◽  
George M. Giambasu ◽  
...  

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.


1999 ◽  
Vol 74 (2) ◽  
pp. 145-158 ◽  
Author(s):  
GILEAN A. T. McVEAN ◽  
BRIAN CHARLESWORTH

Patterns of synonymous codon usage are determined by the forces of mutation, selection and drift. We elaborate on previous population genetic models of codon usage to incorporate parameters of population polymorphism, and demonstrate that the degree of codon bias expected in a single sequence picked at random from the population is accurately predicted by previous models, irrespective of population polymorphism. This new model is used to explore the relationships between synonymous codon usage, nucleotide site diversity and the rate of substitution. We derive the equilibrium frequency distribution of weakly selected segregating sites under the infinite-sites model, and the expected nucleotide site diversity. Contrary to intuition, levels of silent-site diversity can increase with the strength of selection acting on codon usage. We also predict the effects of background selection on statistics of synonymous codon usage and derive simple formulae to predict patterns of codon usage at amino acids with more than two synonymous codons, and the effects of variation in selection coefficient between sites within a gene. We show that patterns of silent-site variation and synonymous codon usage on the X chromosome and autosomes in Drosophila are compatible with recessivity of the fitness effects of unpreferred codons. Finally, we suggest that there still exist considerable discrepancies between current models and data.


Genetics ◽  
2001 ◽  
Vol 159 (1) ◽  
pp. 347-358
Author(s):  
Brian R Morton

Abstract A previously employed method that uses the composition of noncoding DNA as the basis of a test for selection between synonymous codons in plastid genes is reevaluated. The test requires the assumption that in the absence of selective differences between synonymous codons the composition of silent sites in coding sequences will match the composition of noncoding sites. It is demonstrated here that this assumption is not necessarily true and, more generally, that using compositional properties to draw inferences about selection on silent changes in coding sequences is much more problematic than commonly assumed. This is so because selection on nonsynonymous changes can influence the composition of synonymous sites (i.e., codon usage) in a complex manner, meaning that the composition biases of different silent sites, including neutral noncoding DNA, are not comparable. These findings also draw into question the commonly utilized method of investigating how selection to increase translation accuracy influences codon usage. The work then focuses on implications for studies that assess codon adaptation, which is selection on codon usage to enhance translation rate, in plastid genes. A new test that does not require the use of noncoding DNA is proposed and applied. The results of this test suggest that far fewer plastid genes display codon adaptation than previously thought.


2013 ◽  
Vol 641-642 ◽  
pp. 606-614
Author(s):  
Xiao Huan Hu ◽  
Ming Shu Wang ◽  
An Chun Cheng

The Duck Plague Virus (DPV) US5 gene was identified by constructing the DPV genomic library, the synonymous codon usage in the US5 gene of DPV and 11 reference herpesviruses have been investigated by using the CodonW 1.4 program, CUSP (create a codon usage table) program and CHIPS (calculated ENC value) of EMBOSS (The European Molecular Biology Open Software Suite). The results reveals that the synonymous codons with A and T at the third codon positon have widely usage in the codon of US5 gene of DPV. G + C compositional constraint is the main factor that determines the codon usage bias in US5 gene. In addition, rare condons analysis showed that there are 75 rare condons (13.9%) in the ORF of the DPV US5 gene on line (http//:www.kazusa.or.jp/codon), There were 20 codons showing distinct usage differences between DPV with Escherichia coli, 19 between DPV and yeast, 25 between DPV and Human. Therefore the yeast expression system may be suitable for the expression of DPV US5 gene.


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