scholarly journals Intragenomic variation in mutation biases causes underestimation of selection on synonymous codon usage

2021 ◽  
Author(s):  
Alexander L Cope ◽  
Premal Shah
Keyword(s):  
Population Genetics ◽  
Natural Selection ◽  
Codon Usage ◽  
Codon Bias ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Mutation Bias ◽  
Biased Gene Conversion ◽  
Intragenomic Variation ◽  
The Impact

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.

Host Adaptation of Codon Usage in SARS-CoV-2 From Mammals Indicate Natural Selection

2021 ◽  
Author(s):  
Yanan Fu ◽  
Yanping Huang ◽  
Jingjing Rao ◽  
Feng Zeng ◽  
Ruiping Yang ◽  
...  
Keyword(s):  
Natural Selection ◽  
Codon Usage ◽  
Binding Affinity ◽  
Codon Bias ◽  
Synonymous Codon ◽  
Host Adaptation ◽  
Synonymous Codon Usage ◽  
Mutation Pressure ◽  
Usage Analysis ◽  
Human Receptor

Abstract The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, spread across hosts from humans to animals, transmitting particularly effectively in mink. How SARS-CoV-2 selects and evolves in the host, and the differences in the evolution of different animals are still unclear. To analysis the mutation and codon usage bias of SARS-CoV-2 in infected humans and animals. The SARS-CoV-2 sequence in mink (Mink-SARS2) and binding energy with receptor were calculated compared with human. The relative synonymous codon usage of viral encoded gene was analyzed to characterize the differences and the evolutionary characteristics. A synonymous codon usage analysis showed that SARS-CoV-2 is optimized to adapt in the animals in which it is currently reported, and all of the animals showed decreased adaptability relative to that of humans, except for mink. The neutrality plot showed that the effect of natural selection on different SARS-CoV-2 sequences is stronger than mutation pressure. A binding affinity analysis indicated that the spike protein of the SARS-CoV-2 variant in mink showed a greater preference for binding with the mink receptor ACE2 than with the human receptor, especially as the mutation Y453F and N501T in Mink-SARS2 lead to improvement of binding affinity for mink receptor. In summary, mutations Y453F and N501T in Mink-SARS2 lead to improvement of binding affinity with mink receptor, indicating possible natural selection and current host adaptation. Monitoring the variation and codon bias of SARS-CoV-2 provides a theoretical basis for tracing the epidemic, evolution and cross-species spread of SARS-CoV-2.

scholarly journals Quantifying shifts in natural selection on codon usage between protein regions: A population genetics approach

2020 ◽  
Author(s):  
Alexander L. Cope ◽  
Michael A. Gilchrist
Keyword(s):  
Population Genetics ◽  
Natural Selection ◽  
Protein Structure ◽  
Codon Usage ◽  
Synonymous Codon ◽  
Empirical Studies ◽  
Protein Structures ◽  
Synonymous Codon Usage ◽  
Genome Wide ◽  
Computational Analyses

AbstractEmpirical studies indicate changes to synonymous codon usage can impact protein folding. However, genome-wide computational analyses attempting to establish a more general relationship between codon usage and protein structure have often led to contradictory results. Using a population genetics model, we quantified codon-specific shifts in natural selection across and within protein structures, revealing a complex relationship between codon usage and protein structure. However, these shifts are small, suggesting differences in selection related to protein structure are either very weak or apply to relatively few codons. Using a previously published result, we demonstrate how tests for selection on codon usage can be confounded when failing to account for amino acid biases and gene expression. This work demonstrates the value of using population genetics-based models to quantify and tests for shifts in selection on codon usage. Extensions to this approach are discussed.

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.

scholarly journals Natural Selection Determines Synonymous Codon Usage Patterns of Neuraminidase (NA) Gene of the Different Subtypes of Influenza A Virus in Canada

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Youhua Chen
Keyword(s):  
Natural Selection ◽  
Codon Usage ◽  
Influenza A Virus ◽  
Influenza A ◽  
Synonymous Codon ◽  
Phylogenetic Signal ◽  
Synonymous Codon Usage ◽  
Usage Patterns ◽  
Na Sequences ◽  
Na Gene

Synonymous codon usage patterns of neuraminidase (NA) gene of 64 subtypes (one is a mixed subtype) of influenza A virus found in Canada were analyzed. In total, 1422 NA sequences were analyzed. Among the subtypes, H1N1 is the prevailing one with 516 NCBI accession records, followed by H3N2, H3N8, and H4N6. The year of 2009 has the highest report records for the NA sequences in Canada, corresponding to the 2009 pandemic event. Correspondence analysis on the RSCU values of the four major subtypes showed that they had distinct clustering patterns in the two-dimensional scatter plot, indicating that different subtypes of IAV utilized different preferential codons. This subtype clustering pattern implied the important influence of natural selection, which could be further evidenced by an extremely flattened regression line in the neutrality plot (GC12 versus G3s plot) and a significant phylogenetic signal on the distribution of different subtypes in the clades of the phylogenetic tree (λ statistic). In conclusion, different subtypes of IAV showed an evolutionary differentiation on choosing different optimal codons. Natural selection played a deterministic role to structure IAV codon usage patterns in Canada.

scholarly journals Comprehensive Analysis of Codon Usage on Porcine Astrovirus

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 991
Author(s):  
Huiguang Wu ◽  
Zhengyu Bao ◽  
Chunxiao Mou ◽  
Zhenhai Chen ◽  
Jingwen Zhao
Keyword(s):  
Natural Selection ◽  
Codon Usage ◽  
Synonymous Codon ◽  
Similarity Index ◽  
Synonymous Codon Usage ◽  
Codon Usage Pattern ◽  
Broad Host Range ◽  
Mutation Pressure ◽  
Porcine Astrovirus ◽  
Usage Patterns

Porcine astrovirus (PAstV), associated with mild diarrhea and neurological disease, is transmitted in pig farms worldwide. The purpose of this study is to elucidate the main factors affecting codon usage to PAstVs. Phylogenetic analysis showed that the subtype PAstV-5 sat at the bottom of phylogenetic tree, followed by PAstV-3, PAstV-1, PAstV-2, and PAstV-4, indicating that the five existing subtypes (PAstV1-PAstV5) may be formed by multiple differentiations of PAstV ancestors. A codon usage bias was found in the PAstVs-2,3,4,5 from the analyses of effective number of codons (ENC) and relative synonymous codon usage (RSCU). Nucleotides A/U are more frequently used than nucleotides C/G in the genome CDSs of the PAstVs-3,4,5. Codon usage patterns of PAstV-5 are dominated by mutation pressure and natural selection, while natural selection is the main evolutionary force that affects the codon usage pattern of PAstVs-2,3,4. The analyses of codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) showed the codon usage similarities between the PAstV and animals might contribute to the broad host range and the cross-species transmission of astrovirus. Our results provide insight into understanding the PAstV evolution and codon usage patterns.

scholarly journals Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 927-935 ◽  
Author(s):  
H Akashi
Keyword(s):  
Drosophila Melanogaster ◽  
Natural Selection ◽  
Amino Acid ◽  
Codon Usage ◽  
Protein Function ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Drosophila Virilis ◽  
Codon Preference ◽  
Translational Accuracy

Abstract I present evidence that natural selection biases synonymous codon usage to enhance the accuracy of protein synthesis in Drosophila melanogaster. Since the fitness cost of a translational misincorporation will depend on how the amino acid substitution affects protein function, selection for translational accuracy predicts an association between codon usage in DNA and functional constraint at the protein level. The frequency of preferred codons is significantly higher at codons conserved for amino acids than at nonconserved codons in 38 genes compared between D. melanogaster and Drosophila virilis or Drosophila pseudoobscura (Z = 5.93, P < 10(-6)). Preferred codon usage is also significantly higher in putative zinc-finger and homeodomain regions than in the rest of 28 D. melanogaster transcription factor encoding genes (Z = 8.38, P < 10(-6)). Mutational alternatives (within-gene differences in mutation rates, amino acid changes altering codon preference states, and doublet mutations at adjacent bases) do not appear to explain this association between synonymous codon usage and amino acid constraint.

scholarly journals The Effects of the Context-Dependent Codon Usage Bias on the Structure of the nsp1αof Porcine Reproductive and Respiratory Syndrome Virus

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yao-zhong Ding ◽  
Ya-nan You ◽  
Dong-jie Sun ◽  
Hao-tai Chen ◽  
Yong-lu Wang ◽  
...  
Keyword(s):  
Codon Usage ◽  
Codon Bias ◽  
Structural Information ◽  
Synonymous Codon ◽  
Data Bank ◽  
Synonymous Codon Usage ◽  
Respiratory Syndrome Virus ◽  
Translation Speed ◽  
Context Dependent ◽  
Insight Into

The information about the crystal structure of porcine reproductive and respiratory syndrome virus (PRRSV) leader protease nsp1αis available to analyze the roles of tRNA abundance of pigs and codon usage of thensp1αgene in the formation of this protease. The effects of tRNA abundance of the pigs and the synonymous codon usage and the context-dependent codon bias (CDCB) of thensp1αon shaping the specific folding units (α-helix,β-strand, and the coil) in the nsp1αwere analyzed based on the structural information about this protease from protein data bank (PDB: 3IFU) and thensp1αof the 191 PRRSV strains. By mapping the overall tRNA abundance along thensp1α, we found that there is no link between the fluctuation of the overall tRNA abundance and the specific folding units in the nsp1α, and the low translation speed of ribosome caused by the tRNA abundance exists in thensp1α. The strong correlation between some synonymous codon usage and the specific folding units in the nsp1αwas found, and the phenomenon of CDCB exists in the specific folding units of the nsp1α. These findings provide an insight into the roles of the synonymous codon usage and CDCB in the formation of PRRSV nsp1αstructure.

scholarly journals Natural Selection Plays an Important Role in Shaping the Codon Usage of Structural Genes of the Viruses Belonging to the Coronaviridae Family

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 3
Author(s):  
Dimpal A. Nyayanit ◽  
Pragya D. Yadav ◽  
Rutuja Kharde ◽  
Sarah Cherian
Keyword(s):  
Natural Selection ◽  
Codon Usage ◽  
Codon Position ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Codon Usage Pattern ◽  
Structural Genes ◽  
Effective Number Of Codons ◽  
Neutrality Plot

Viruses belonging to the Coronaviridae family have a single-stranded positive-sense RNA with a poly-A tail. The genome has a length of ~29.9 kbps, which encodes for genes that are essential for cell survival and replication. Different evolutionary constraints constantly influence the codon usage bias (CUB) of different genes. A virus optimizes its codon usage to fit the host environment on which it savors. This study is a comprehensive analysis of the CUB for the different genes encoded by viruses of the Coronaviridae family. Different methods including relative synonymous codon usage (RSCU), an Effective number of codons (ENc), parity plot 2, and Neutrality plot, were adopted to analyze the factors responsible for the genetic evolution of the Coronaviridae family. Base composition and RSCU analyses demonstrated the presence of A-ended and U-ended codons being preferred in the 3rd codon position and are suggestive of mutational selection. The lesser ENc value for the spike ‘S’ gene suggests a higher bias in the codon usage of this gene compared to the other structural genes. Parity plot 2 and neutrality plot analyses demonstrate the role and the extent of mutational and natural selection towards the codon usage pattern. It was observed that the structural genes of the Coronaviridae family analyzed in this study were at the least under 84% influence of natural selection, implying a major role of natural selection in shaping the codon usage.

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.

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