Comparative studies of codon usage profile of Anisakis simplex (Nematoda) and Carassius gibelio (Prussian carp)

Aim: The aim of the present study was to understand the molecular relationship between nematode (parasite) and fish (host) through codon usage bias (CUB) analysis. Methodology: The Codon usage bias analysis has been performed in fish Carassius gibelio (Prussian carp) and nematode fish parasite Anisakis simplex. The complete coding sequences (CDS) of C. gibelio (Prussian carp) and A. simplex (Nematode) were retrieved from National Center for Biotechnology Information and followed to that we have performed bioinformatics analysis to understand the codon usage pattern between host and parasite. Results: Different CUB indices like Relative synonymous codon usage (RSCU), Effective number of codons (ENC), Codon adaptation index (CAI) and Codon bias index (CBI) revealed a similar pattern in the codon usage in C. gibelio and A. simplex. In addition, inclusive analysis using different plots (ENC, parity, neutrality) had shown the influence of both the evolutionary forces i.e mutational and translational selection on codon usage pattern. This describes the role of evolutionary forces in determining the conserved genome to establish species-specific function-level differences for efficient survival. Interpretation: The present study elucidated the association between Carassiusgibelio (host) and Anisakis simplex (parasite) based on the similar pattern of codon usage bias between both the species.

Distinct responses to rare codons in select Drosophila tissues

Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wide screen in Drosophila melanogaster for distinct tissue responses to codon usage bias. These reporters reveal a cliff-like decline of protein expression near the limit of rare codon usage in endogenously expressed Drosophila genes. Near the edge of this limit, however, we find the testis and brain are uniquely capable of expressing rare codon-enriched reporters. We define a new metric of tissue-specific codon usage, the tissue-apparent Codon Adaptation Index, to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis. We further demonstrate a role for rare codons in restricting protein expression of an evolutionarily young gene, RpL10Aa, to the Drosophila testis. Rare codon-mediated restriction of this testis-specific protein is critical for female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.

Comprehensive Analysis of Codon Usage Patterns in Chinese Porcine Circoviruses Based on Their Major Protein-Coding Sequences

Porcine circoviruses (PCVs) are distributed in swine herds worldwide and represent a threat to the health of domestic pigs and the profits of the swine industry. Currently, four PCV species, including PCV-1, PCV-2, PCV-3 and PCV-4, have been identified in China. Considering the ubiquitous characteristic of PCVs, the new emerged PCV-4 and the large scale of swine breeding in China, an overall analysis on codon usage bias for Chinese PCV sequences was performed by using the major proteins coding sequences (ORF1 and ORF2) to better understand the relationship of these viruses with their host. The data from genome nucleotide frequency composition and relative synonymous codon usage (RSCU) analysis revealed an overrepresentation of AT pair and the existence of a certain codon usage bias in all PCVs. However, the values of an effective number of codons (ENC) revealed that the bias was of low magnitude. Principal component analysis, ENC-plot, parity rule two analysis and correlation analysis suggested that natural selection and mutation pressure were both involved in the shaping of the codon usage patterns of PCVs. However, a neutrality plot revealed a stronger effect of natural selection than mutation pressure on codon usage patterns. Good host adaptation was also shown by the codon adaptation index analysis for all these viruses. Interestingly, obtained data suggest that PCV-4 might be more adapted to its host compared to other PCVs. The present study obtained insights into the codon usage pattern of PCVs based on ORF1 and ORF2, which further helps the understanding the molecular evolution of these swine viruses.

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

Two 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.

Human cellular homeostasis buffers trans-acting translational effects of heterologous gene expression with very different codon usage bias

The frequency of synonymous codons in protein coding genes is non-random and varies both between species and between genes within species. Whether this codon usage bias (CUBias) reflects underlying neutral mutational processes or is instead shaped by selection remains an open debate, especially regarding the role of selection for enhanced protein production. Variation in CUBias of a gene (be it natural synonymous mutations or biotechnological synonymous recoding) can have an enormous impact on its expression by diverse cis- acting mechanisms. But expression of genes with extreme CUBias can also lead to strong phenotypic effects by altering the overall intracellular translation homeostasis via competition for ribosomal machinery or tRNA depletion. In this study, we expressed at high levels in human cells six different synonymous versions of a gene and used matched transcriptomic and proteomic data to evaluate the impact of CUBias of the heterologous gene on the translation of cellular transcripts. Our experimental design focused specifically on differences during translation elongation. Response to expression of the different synonymous sequences was assessed by various approaches, ranging from analyses performed on a per-gene basis to more integrated approaches of the cell as a whole. We observe that the transcriptome displayed substantial changes as a result of heterologous gene expression by triggering an intense antiviral and inflammatory response, but that changes in the proteomes were very modest. Most importantly we notice that changes in translation efficiency of cellular transcripts were not associated with the direction of the CUBias of the heterologous sequences, thereby providing only limited support for trans- acting effects of synonymous changes. We interpret that, in human cells in culture, changes in CUBias can lead to important cis- acting effects in gene expression, but that cellular homeostasis can buffer the phenotypic impact of overexpression of heterologous genes with extreme CUBias.