Mutation Bias is the Driving Force of Codon Usage in the Gallus gallus genome

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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An analysis of codon usage in mammals: Selection or mutation bias?

Journal of Molecular Evolution ◽

10.1007/bf02103136 ◽

1991 ◽

Vol 33 (5) ◽

pp. 442-449 ◽

Cited By ~ 54

Author(s):

Adam C. Eyre-Walker

Keyword(s):

Codon Usage ◽

Mutation Bias

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Comparisons of Coding and Noncoding Sequences to infer the Origin of Codon usage Bias

10.1101/174359 ◽

2017 ◽

Author(s):

Prashant Mainali ◽

Sobita Pathak

Keyword(s):

Codon Usage ◽

Codon Usage Bias ◽

Gc Content ◽

Mutation Bias ◽

Translation Process ◽

Noncoding Regions ◽

Coding Regions ◽

Synonymous Codons ◽

Shed Light

ABSTRACTCodon usage bias is the preferential use of the subset of synonymous codons during translation. In this paper, the comparisons of normalized entropy and GC content between the sequence of coding regions of Escherichia coli k12 and noncoding regions (ncRNA, rRNA) of various organisms were done to shed light on the origin of the codon usage bias.The normalized entropy of the coding regions was found significantly higher than the noncoding regions, suggesting the role of the translation process in shaping codon usage bias. Further, when the position specific GC content of both coding and noncoding regions was analyzed, the GC2 content in coding regions was lower than GC1 and GC2 while in noncoding regions, the GC1, GC2, GC3 contents were approximately equal. This discrepancy is explained by the biased mutation coupled with the presence and absence of selection pressure. The accumulation of CG content occurs in the sequences due to mutation bias in DNA repair and recombination process. In noncoding regions, the mutation is harmful and thus, selected against while due to the degeneracy of codons in coding regions, a mutation in GC3 is neutral and hence, not selected. Thus, the accumulation of GC content occurs in coding regions, and thus codon usage bias occurs.

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Context-Dependent Mutation Dynamics, Not Selection, Explains the Codon Usage Bias of Most Angiosperm Chloroplast Genes

Journal of Molecular Evolution ◽

10.1007/s00239-021-10038-w ◽

2021 ◽

Author(s):

Brian R. Morton

Keyword(s):

Codon Usage ◽

Significant Role ◽

Codon Usage Bias ◽

Base Composition ◽

Context Effects ◽

Chloroplast Genes ◽

Mutation Bias ◽

Highly Expressed Genes ◽

Context Dependent ◽

Mutation Dynamics

AbstractTwo competing proposals about the degree to which selection affects codon usage of angiosperm chloroplast genes are examined. The first, based on observations that codon usage does not match expectations under the naïve assumption that base composition will be identical at all neutral sites, is that selection plays a significant role. The second is that codon usage is determined almost solely by mutation bias and drift, with selection influencing only one or two highly expressed genes, in particular psbA. First it is shown that, as a result of an influence of neighboring base composition on mutation dynamics, compositional biases are expected to be widely divergent at different sites in the absence of selection. The observed mutation properties are then used to predict expected neutral codon usage biases and to show that observed deviations from the naïve expectations are in fact expected given the context-dependent mutational dynamics. It is also shown that there is a match between the observed and expected codon usage when context effects are taken into consideration, with psbA being a notable exception. Overall, the data support the model that selection is not a widespread factor affecting the codon usage of angiosperm chloroplast genes and highlight the need to have an accurate model of mutational dynamics.

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Comprehensive Analysis of Codon Usage on Rabies Virus and Other Lyssaviruses

International Journal of Molecular Sciences ◽

10.3390/ijms19082397 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2397 ◽

Cited By ~ 4

Author(s):

Xu Zhang ◽

Yuchen Cai ◽

Xiaofeng Zhai ◽

Jie Liu ◽

Wen Zhao ◽

...

Keyword(s):

Codon Usage ◽

Rabies Virus ◽

Driving Force ◽

Control Strategies ◽

Comprehensive Analysis ◽

Codon Usage Pattern ◽

Usage Pattern ◽

Effective Number ◽

Usage Patterns ◽

Effective Number Of Codons

Rabies virus (RABV) and other lyssaviruses can cause rabies and rabies-like diseases, which are a persistent public health threat to humans and other mammals. Lyssaviruses exhibit distinct characteristics in terms of geographical distribution and host specificity, indicative of a long-standing diversification to adapt to the environment. However, the evolutionary diversity of lyssaviruses, in terms of codon usage, is still unclear. We found that RABV has the lowest codon usage bias among lyssaviruses strains, evidenced by its high mean effective number of codons (ENC) (53.84 ± 0.35). Moreover, natural selection is the driving force in shaping the codon usage pattern of these strains. In summary, our study sheds light on the codon usage patterns of lyssaviruses, which can aid in the development of control strategies and experimental research.

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Comparative Analysis of Codon Usage and tRNA in Mitochondrial Genomes of Gallus Gallus

Avian Biology Research ◽

10.3184/175815509x12473915395956 ◽

2009 ◽

Vol 2 (3) ◽

pp. 133-141

Author(s):

Tangjie Zhang ◽

Hong Chang ◽

Yuzhi Liu ◽

Huifang Li ◽

Kuanwei Chen

Keyword(s):

Codon Usage ◽

Synonymous Codon ◽

Gallus Gallus ◽

Mitochondrial Genes ◽

Synonymous Codon Usage ◽

Relative Synonymous Codon Usage ◽

Mutational Bias ◽

Mitochondrial Genomes ◽

The Third ◽

Codon Positions

Codon usage in mitochondrial genes of 11 Gallus gallus and two Anatidae species was analysed to determine the general patterns in codon choice of Callus gallus species. C3 contents were higher in Gallus gallus than in mammalian mitochondrial genomes that encode protein codon positions. The high C3 contents of Callus gallus might be the result of relatively strong mutational bias that occurred in the lineage of the Callus gallus species. A and C ending codons were detected as the “preferred 77 codons in Callus gallus and Anatidae. The NNR codon families are dominated by the A-ending codons, the NNY codon families are dominated by the C-ending codons and the NNN codon families are dominated by the A-ending or the C-ending codons. A comparison of the relative synonymous codon usage (RSCU) and synonymous codon families (SCF) of tRNA and proteins was made, and two groups can be classified by SCF. The codon usage in Callus gallus species indicates that codons containing A or C at the third position are used preferentially, regardless of whether corresponding tRNAs are encoded in the mtDNA. In both Callus gallus and Anatidae species mtDNA, codon usage biases are highly related to CC-ending binucleotide condons.

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Explaining complex codon usage patterns with selection for translational efficiency, mutation bias, and genetic drift

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1016719108 ◽

2011 ◽

Vol 108 (25) ◽

pp. 10231-10236 ◽

Cited By ~ 94

Author(s):

P. Shah ◽

M. A. Gilchrist

Keyword(s):

Codon Usage ◽

Genetic Drift ◽

Translational Efficiency ◽

Mutation Bias ◽

Usage Patterns ◽

Selection For

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Analysis of the Codon Usage Pattern of HA and NA Genes of H7N9 Influenza A Virus

International Journal of Molecular Sciences ◽

10.3390/ijms21197129 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7129

Author(s):

Jiumeng Sun ◽

Wen Zhao ◽

Ruyi Wang ◽

Wenyan Zhang ◽

Gairu Li ◽

...

Keyword(s):

Influenza Virus ◽

Natural Selection ◽

Codon Usage ◽

Selection Pressure ◽

Gallus Gallus ◽

Codon Usage Pattern ◽

Usage Pattern ◽

H7n9 Influenza Virus ◽

Evolutionary Changes ◽

H7n9 Influenza

Novel H7N9 influenza virus transmitted from birds to human and, since March 2013, it has caused five epidemic waves in China. Although the evolution of H7N9 viruses has been investigated, the evolutionary changes associated with codon usage are still unclear. Herein, the codon usage pattern of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), was studied to understand the evolutionary changes in relation to host, epidemic wave, and pathogenicity. Both genes displayed a low codon usage bias, with HA higher than NA. The codon usage was driven by mutation pressure and natural selection, although the main contributing factor was natural selection. Additionally, the codon adaptation index (CAI) and deoptimization (RCDI) illustrated the strong adaptability of H7N9 to Gallus gallus. Similarity index (SiD) analysis showed that Homo sapiens posed a stronger selection pressure than Gallus gallus. Thus, we assume that this may be related to the gradual adaptability of the virus to human. In addition, the host strong selection pressure was validated based on CpG dinucleotide content. In conclusion, this study analyzed the usage of codons of two genes of H7N9 and expanded our understanding of H7N9 host specificity. This aids into the development of control measures against H7N9 influenza virus.

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