scholarly journals Analysis of Mutation Bias in Shaping Codon Usage Bias and Its Association with Gene Expression Across Species

10.29007/87r9 ◽  
2020 ◽  
Author(s):  
Zhixiu Lu ◽  
Michael Gilchrist ◽  
Scott Emrich

Codon usage bias has been known to reflect the expression level of a protein-coding gene under the evolutionary theory that selection favors certain synonymous codons. Although measuring the effect of selection in simple organisms such as yeast and E. coli has proven to be effective and accurate, codon-based methods perform less well in plants and humans. In this paper, we extend a prior method that incorporates another evolutionary factor, namely mutation bias and its effect on codon usage. Our results indicate that prediction of gene expression is significantly improved under our framework, and suggests that quantification of mutation bias is essential for fully understanding synonymous codon usage. We also propose an improved method, namely MLE-Φ, with much greater computation efficiency and a wider range of applications. An implementation of this method is provided at https://github.com/luzhixiu1996/MLE- Phi.

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.


2011 ◽  
Vol 57 (12) ◽  
pp. 1016-1023 ◽  
Author(s):  
Xue Lian Luo ◽  
Jian Guo Xu ◽  
Chang Yun Ye

In this study, we analysed synonymous codon usage in Shigella flexneri 2a strain 301 (Sf301) and performed a comparative analysis of synonymous codon usage patterns in Sf301 and other strains of Shigella and Escherichia coli . Although there was a significant variety in codon usage bias among different Sf301 genes, there was a slight but observable codon usage bias that could primarily be attributable to mutational pressure and translational selection. In addition, the relative abundance of dinucleotides in Sf301 was observed to be independent of the overall base composition but was still caused by differential mutational pressure; this also shaped codon usage. By comparing the relative synonymous codon usage values across different Shigella and E. coli strains, we suggested that the synonymous codon usage pattern in the Shigella genomes was strain specific. This study represents a comprehensive analysis of Shigella codon usage patterns and provides a basic understanding of the mechanisms underlying codon usage bias.


2011 ◽  
Vol 204-210 ◽  
pp. 649-662 ◽  
Author(s):  
Ying Wu ◽  
An Chun Cheng ◽  
Ming Shu Wang ◽  
De Kang Zhu ◽  
Xiao Yue Chen

The analysis of codon usage may improve our understanding of the evolution and pathogenesis of DEV(Duck enteritis virus) and allow reengineering of target gene to improve their expression for gene therapy.In this study,we calculated the codon usage bias in DEV UL55 gene and performed a comparative analysis of synonymous codon usage patterns in other 26 related viruses by EMBOSS CUSP program and Codon W on line.Moreover,statistical methods were used to investigate the correlations of these related parameters. By comparing synonymous codon usage patterns in different viruses,we observed that synonymous codon usage pattern in these virus is virus specific and phylogenetically conserved, with a strong bias towards the codons with A and T at the third codon position. Phylogenetic analysis based on codon usage pattern suggested that DEV UL55 gene was clustered with the avian Alphaherpesvirus but diverged to form a single branch. The Neutrality-plot suggested GC12 and GC3s adopt the same mutation pattern,meanwhile,the ENC-plot revealed that the genetic heterogeneity in UL55 genes is constrained by the G+C content, while translational selection and gene length have no or micro effect on the variations of synonymous codon usage in these virus genes.Furthermore, we compared the codon preferences of DEV with those of E. coli, yeast and Homo sapiens.Data suggested the eukaryotes system such as human system may be more suitable for the expression of DEV UL55 gene in vitro. If the yeast and E. coli expression system are wanted for the expression of DEV UL55 gene ,codon optimization of the DEV UL55 gene may be required.


2021 ◽  
Author(s):  
Chao Xu ◽  
◽  
Wen B. Bao ◽  
Sheng L. Wu ◽  
Zheng C. Wu ◽  
...  

Enterotoxigenic E. coli is an important zoonotic pathogen causing diarrhea in human and newborn animals. α - (1,2) fucosyltransferase 2 (FUT2) is closely associated with the formation of pathogenic receptors of Enterotoxigenic E. coli. Codon usage bias analysis can help to better understand the molecular mechanisms and evolutionary relationships of a particular gene. In order to understand the codon usage pattern of FUT2 gene, FUT2 gene coding sequences of nine species were selected from GenBank database for calculating the nucleotide composition (GC content) and genetic indices including effective number of codons, relative synonymous codon usage and relative codon usage bias using R software, in order to analyze codon usage bias and base composition in FUT2 gene from different species. The results showed that the codon usage of FUT2 gene in different species was affected by GC bias, especially GC frequency at the third position of codon (GC3). Most of the optimal codons were biased towards the G/C-ending types. GCC, CUG, UCC, GUG and AUC showed the highest relative synonymous codon usage value among different species, belonging to the most dominant codons. The usage characteristic of the codens for FUT2 gene in Sus scrofa was similar to that of Bos taurus; Homo sapiens was similar to Pan troglodytes. Effective number of codons was significantly, negatively correlated with GC3, and the relative higher frequency of optimal codon implied that FUT2 genes from different species had a strong bias in codon usage.


2014 ◽  
Vol 13 (3) ◽  
pp. 7347-7355 ◽  
Author(s):  
X.X. Ma ◽  
Y.P. Feng ◽  
J.L. Liu ◽  
L. Chen ◽  
Y.Q. Zhao ◽  
...  

2021 ◽  
Author(s):  
Alexander L Cope ◽  
Premal Shah

Patterns of non-uniform usage of synonymous codons (codon bias) varies across genes in an organism and across species from all domains of life. The bias in codon usage is due to a combination of both non-adaptive (e.g. mutation biases) and adaptive (e.g. natural selection for translation efficiency/accuracy) evolutionary forces. Most population genetics models quantify the effects of mutation bias and selection on shaping codon usage patterns assuming a uniform mutation bias across the genome. However, mutation biases can vary both along and across chromosomes due to processes such as biased gene conversion, potentially obfuscating signals of translational selection. Moreover, estimates of variation in genomic mutation biases are often lacking for non-model organisms. Here, we combine an unsupervised learning method with a population genetics model of synonymous codon bias evolution to assess the impact of intragenomic variation in mutation bias on the strength and direction of natural selection on synonymous codon usage across 49 Saccharomycotina budding yeasts. We find that in the absence of a priori information, unsupervised learning approaches can be used to identify regions evolving under different mutation biases. We find that the impact of intragenomic variation in mutation bias varies widely, even among closely-related species. We show that the overall strength and direction of selection on codon usage can be underestimated by failing to account for intragenomic variation in mutation biases. Interestingly, genes falling into clusters identified by machine learning are also often physically clustered across chromosomes, consistent with processes such as biased gene conversion. Our results indicate the need for more nuanced models of sequence evolution that systematically incorporate the effects of variable mutation biases on codon frequencies.


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