Analysis of SARS-CoV-2 synonymous codon usage evolution throughout the COVID-19 pandemic.

SARS-CoV-2, the seventh coronavirus known to infect humans, can cause severe life-threatening respiratory pathologies. To better understand SARS-CoV-2 evolution, genome-wide analyses have been made, including the general characterization of its codons usage profile. Here we present a bioinformatic analysis of the evolution of SARS-CoV-2 codon usage over time using complete genomes collected since December 2019. Our results show that SARS-CoV-2 codon usage pattern is antagonistic to, and it is getting farther away from that of the human host. Further, a selection of deoptimized codons over time, which was accompanied by a decrease in both the codon adaptation index and the effective number of codons, was observed. All together, these findings suggest that SARS-CoV-2 could be evolving, at least from the perspective of the synonymous codon usage, to become less pathogenic.

Strategies and Patterns of Codon Bias in Molluscum Contagiosum Virus

Trends associated with codon usage in molluscum contagiosum virus (MCV) and factors governing the evolution of codon usage have not been investigated so far. In this study, attempts were made to decipher the codon usage trends and discover the major evolutionary forces that influence the patterns of codon usage in MCV with special reference to sub-types 1 and 2, MCV-1 and MCV-2, respectively. Three hypotheses were tested: (1) codon usage patterns of MCV-1 and MCV-2 are identical; (2) SCUB (synonymous codon usage bias) patterns of MCV-1 and MCV-2 slightly deviate from that of human host to avoid affecting the fitness of host; and (3) translational selection predominantly shapes the SCUB of MCV-1 and MCV-2. Various codon usage indices viz. relative codon usage value, effective number of codons and codon adaptation index were calculated to infer the nature of codon usage. Correspondence analysis and correlation analysis were performed to assess the relative contribution of silent base contents and significance of codon usage indices in defining bias in codon usage. Among the tested hypotheses, only the second and third hypotheses were accepted.

Comparative analysis of codon usage patterns of FUT2 from different species

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.

The mitochondrial genomes of Tortricidae: nucleotide composition, gene variation and phylogenetic performance

Background Mitochondrial genomes (mitogenomes) have greatly improved our understanding of the backbone phylogeny of Lepidoptera, but few studies on comparative mitogenomics below the family level have been conducted. Here, we generated 13 mitogenomes of eight tortricid species, reannotated 27 previously reported mitogenomes, and systematically performed a comparative analysis of nucleotide composition, gene variation and phylogenetic performance. Results The lengths of completely sequenced mitogenomes ranged from 15,440 bp to 15,778 bp, and the gene content and organization were conserved in Tortricidae and typical for Lepidoptera. Analyses of AT-skew and GC-skew, the effective number of codons and the codon bias index all show a base bias in Tortricidae, with little heterogeneity among the major tortricid groups. Variations in the divergence rates among 13 protein-coding genes of the same tortricid subgroup and of the same PCG among tortricid subgroups were detected. The secondary structures of 22 transfer RNA genes and two ribosomal RNA genes were predicted and comparatively illustrated, showing evolutionary heterogeneity among different RNAs or different regions of the same RNA. The phylogenetic uncertainty of Enarmoniini in Tortricidae was confirmed. The synonymy of Bactrini and Olethreutini was confirmed for the first time, with the representative Bactrini consistently nesting in the Olethreutini clade. Nad6 exhibits the highest phylogenetic informativeness from the root to the tip of the resulting tree, and the combination of the third coding positions of 13 protein-coding genes shows extremely high phylogenetic informativeness. Conclusions This study presents 13 mitogenomes of eight tortricid species and represents the first detailed comparative mitogenomics study of Tortricidae. The results further our understanding of the evolutionary architectures of tortricid mitogenomes and provide a basis for future studies of population genetics and phylogenetic investigations in this group.

Sex-Biased Gene Expression and Evolution in the Cerebrum and Syrinx of Chinese Hwamei (Garrulax canorus)

It is common that males and females display sexual dimorphisms, which usually result from sex-biased gene expression. Chinese hwamei (Garrulax canorus) is a good model for studying sex-biased gene expression because the song between the sexes is quite different. In this study, we analyze cerebrum and syrinx sex-biased gene expression and evolution using the de novo assembled Chinese hwamei transcriptome. In both the cerebrum and syrinx, our study revealed that most female-biased genes were actively expressed in females only, while most male-biased genes were actively expressed in both sexes. In addition, both male- and female-biased genes were enriched on the putative Z chromosome, suggesting the existence of sexually antagonistic genes and the insufficient dosage compensation of the Z-linked genes. We also identified a 9 Mb sex linkage region on the putative 4A chromosome which enriched more than 20% of female-biased genes. Resultantly, male-biased genes in both tissues had significantly higher Ka/Ks and effective number of codons (ENCs) than unbiased genes, and this suggested that male-biased genes which exhibit accelerated divergence may have resulted from positive selection. Taken together, our results initially revealed the reasons for the differences in singing behavior between males and females of Chinese hwamei.

Effect of genome composition and codon bias on infectious bronchitis virus evolution and adaptation to target tissues

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.

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

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.

Insights into Comparative Genomics, Codon Usage Bias, and Phylogenetic Relationship of Species from Biebersteiniaceae and Nitrariaceae Based on Complete Chloroplast Genomes

Biebersteiniaceae and Nitrariaceae, two small families, were classified in Sapindales recently. Taxonomic and phylogenetic relationships within Sapindales are still poorly resolved and controversial. In current study, we compared the chloroplast genomes of five species (Biebersteinia heterostemon, Peganum harmala, Nitraria roborowskii, Nitraria sibirica, and Nitraria tangutorum) from Biebersteiniaceae and Nitrariaceae. High similarity was detected in the gene order, content and orientation of the five chloroplast genomes; 13 highly variable regions were identified among the five species. An accelerated substitution rate was found in the protein-coding genes, especially clpP. The effective number of codons (ENC), parity rule 2 (PR2), and neutrality plots together revealed that the codon usage bias is affected by mutation and selection. The phylogenetic analysis strongly supported (Nitrariaceae (Biebersteiniaceae + The Rest)) relationships in Sapindales. Our findings can provide useful information for analyzing phylogeny and molecular evolution within Biebersteiniaceae and Nitrariaceae.

Triplex and other DNA motifs show motif-specific associations with mitochondrial DNA deletions and species lifespan

ABSTRACTThe “theory of resistant biomolecules” posits that long-lived species show resistance to molecular damage at the level of their biomolecules. Here, we test this hypothesis in the context of mitochondrial DNA (mtDNA) as it implies that predicted mutagenic DNA motifs should be inversely correlated with species maximum lifespan (MLS).First, we confirmed that guanine-quadruplex and direct repeat (DR) motifs are mutagenic, as they associate with mtDNA deletions in the human major arc of mtDNA, while also adding mirror repeat (MR) and intramolecular triplex motifs to a growing list of potentially mutagenic features. What is more, triplex motifs showed disease-specific associations with deletions and an apparent interaction with guanine-quadruplex motifs.Surprisingly, even though DR, MR and guanine-quadruplex motifs were associated with mtDNA deletions, their correlation with MLS was explained by the biased base composition of mtDNA. Only triplex motifs negatively correlated with MLS even after adjusting for body mass, phylogeny, mtDNA base composition and effective number of codons.Taken together, our work highlights the importance of base composition for the comparative biogerontology of mtDNA and suggests that future research on mitochondrial triplex motifs is warranted.

Selection constraints determine preference for A/U-ending codons in Taxus contorta

Unequal utilization of synonymous codons is a well-known phenomenon among living organisms. This phenomenon plays a major role in the enhancement of the accuracy and efficiency of translation. Gymnosperms are rarely paid attention in this aspect. Understanding the degree of and determining the forces influencing codon usage bias (CUB) in Taxus contorta, an endangered Himalayan gymnosperm, will prove useful in interpreting the evolutionary characteristics of this species. Using RNAseq data, 93 790 assembled transcripts were clustered into 32 701 unigenes. Around 13 061 full-length sequences were utilized for the analysis of CUB. Compositional properties showed that GC-content ranged from 28.76% to 65.22%, with an average value of 44.28%, suggesting an AT-rich genome. The mean effective number of codons (ENC) value revealed that CUB is not strong in T. contorta. The preferred codons tended to be A/U ending, whereas the avoided codons tended to be G/C ending. A P2 index of 0.54 and a Mutation Responsive Index (MRI) value of –0.02 in addition to the results revealed by the neutrality, ENC, and parity plots showed that natural selection is a predominating factor governing CUB. Mutational pressure, gene length, hydropathiciy, aromaticity, and nucleotide composition influence CUB weakly.