Codon usage, phylogeny and binding energy estimation predict the evolution of SARS-CoV-2.
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ABSTRACT:
SUBMITTER: Calcagnile M
PROVIDER: S-EPMC8610831 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.
| S-EPMC7468442 | biostudies-literature
Project description:BackgroundCOVID-19, as a novel coronavirus disease caused by new coronavirus SARS-CoV-2, spreads all over the world, and brings harm to human in many countries. Humans suffered a lot from both SARS-CoV-2 now and by SARS-CoV in the year 2003. It is important to understand the differences and the relationships between these two types of viruses.ObjectiveTo compare relative synonymous codon usage of ORF1ab gene in SARS-CoV-2 and SARS-CoV, relative synonymous codon usage of their genomes are studied in this paper from the bioinformatics perspective.MethodsThe ORF1ab gene, which is an important non-structural polyprotein coding gene and now used for nucleic acid detection markers in many measurement method, in both SARS-CoV-2 (30 strains) and SARS-CoV (20 strains) are considered to be the research object in the present paper. The relative synonymous codon usage values of the ORF1ab gene are calculated to characterize the differences and the evolutionary characteristics among 50 strains.ResultsThere is a significant difference between SARS-CoV and SARS-CoV-2 when the relative synonymous codon usage value of ORF1ab genes is concerned. The results suggest that codon usage pattern of SARS-CoV is more similar to human than that of the SARS-CoV-2, and that the inner difference in SARS-CoV-2 strains is larger than that of SARS-CoV, which denote the larger diversity exits in the SARS-CoV-2 virus.ConclusionThese results show that the relative synonymous codon usage values in the coronavirus could be used for further research on their evolutionary phenomenon.
| S-EPMC8258482 | biostudies-literature
Project description:The outbreak of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed significant threats to international health. The genetic traits as well as evolutionary processes in this novel coronavirus are not fully characterized, and their roles in viral pathogenesis are yet largely unknown. To get a better picture of the codon architecture of this newly emerging coronavirus, in this study we perform bioinformatic analysis, based on publicly available nucleotide sequences of SARS-CoV-2 along with those of other members of human coronaviruses as well as non-human coronaviruses in different hosts, to take a snapshot of the genome-wide codon usage pattern of SARS-CoV-2 and uncover that all over-represented codons end with A/U and this newly emerging coronavirus has a relatively low codon usage bias, which is shaped by both mutation pressure and natural selection. Additionally, there is slight variation in the codon usage pattern among the SARS-CoV-2 isolates from different geo-locations. Furthermore, the overall codon usage pattern of SARS-CoV-2 is generally similar to that of its phylogenetic relatives among non-human betacoronaviruses such as RaTG13. Taken together, we comprehensively analyze the characteristics of codon usage pattern in SARS-CoV-2 via bioinformatic approaches. The information from this research may not only be helpful to get new insights into the evolution of SARS-CoV-2, but also have potential value for developing coronavirus vaccines.
| S-EPMC7487440 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2.
| S-EPMC7290700 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads all over the world and brings great harm to humans in many countries. Many new SARS-CoV-2 variants appeared during its transmission. In the present study, the Delta variants (B.1.617.2) of SARS-CoV-2, which have appeared in many countries, were considered for analysis. In order to evaluate the evolutionary divergence of the Delta variants(B.1.617.2), the codon usage divergence in Delta variants (B.1.617.2) of SARS-CoV-2 was compared to that of the SARS-CoV-2 genomes emerged before June 2020. All Delta variants (B.1.617.2) and 350 early genomes of SARS-CoV-2 in the NCBI database were downloaded. Codon usage pattern including the basic composition, the GC ratio of the third position (GC3) and the first two positions (GC12) in codons, overall GC contents, the effective number of codons (ENC), the codon bias index (CBI), the relative synonymous codon usage (RSCU) values, etc., of all concerned important gene sequences were all calculated. Codon usage divergence of them was calculated via summing their standard deviations. The results suggested that base compositions in both Delta variants (B.1.617.2) of SARS-CoV-2 and the early SARS-CoV-2 genomes were similar to each other. However, the internal codon usage divergence for most genes in Delta variants (B.1.617.2) was significantly wider than that of SARS-CoV-2. The RSCU values were further used to explore the synonymous and non-synonymous mutations in the sequences of the Delta variants (B.1.617.2), and the results showed the synonymous mutations are more obvious than the non-synonymous in the concerned sequences. The related codon usage divergence analysis is helpful for further study on the adaptability and disease prognosis of the SARS-CoV-2 variants.
| S-EPMC8641433 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus, which also includes severe acute respiratory syndrome-related coronavirus (SARSr-CoV) and Middle East respiratory syndrome-related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses helped identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, we compared the codon usage bias using global correspondence analysis (CA), within-group CA and between-group CA. We found that the bat RaTG13 virus best matched the overall codon usage pattern of SARS-CoV-2 in orf1ab, spike and nucleocapsid genes, while the pangolin P1E virus had a more similar codon usage in membrane gene. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.
| S-EPMC7223271 | biostudies-literature
Project description:Interaction of SARS-CoV-2 spike glycoprotein with the ACE2 cell receptor is very crucial for virus attachment to human cells. Selected mutations in SARS-CoV-2 S-protein are reported to strengthen its binding affinity to mammalian ACE2. The N501T mutation in SARS-CoV-2-CTD furnishes better support to hotspot 353 in comparison with SARS-CoV and shows higher affinity for receptor binding. Recombination analysis exhibited higher recombination events in SARS-CoV-2 strains, irrespective of their geographical origin or hosts. Investigation further supports a common origin among SARS-CoV-2 and its predecessors, SARS-CoV and bat-SARS-like-CoV. The recombination events suggest a constant exchange of genetic material among the co-infecting viruses in possible reservoirs and human hosts before SARS-CoV-2 emerged. Furthermore, a comprehensive analysis of codon usage bias (CUB) in SARS-CoV-2 revealed significant CUB among the S-genes of different beta-coronaviruses governed majorly by natural selection and mutation pressure. Various indices of codon usage of S-genes helped in quantifying its adaptability in other animal hosts. These findings might help in identifying potential experimental animal models for investigating pathogenicity for drugs and vaccine development experiments.
| S-EPMC7953982 | biostudies-literature
Project description:Codon usage bias (CUB)-preferential use of one of the synonymous codons, has been described in a wide range of organisms from bacteria to mammals, but it has not yet been studied in marine phytoplankton. CUB is thought to be caused by weak selection for translational accuracy and efficiency. Weak selection can overpower genetic drift only in species with large effective population sizes, such as Drosophila that has relatively strong CUB, while organisms with smaller population sizes (e.g., mammals) have weak CUB. Marine plankton species tend to have extremely large populations, suggesting that CUB should be very strong. Here we test this prediction and describe the patterns of codon usage in a wide range of diatom species belonging to 35 genera from 4 classes. We report that most of the diatom species studied have surprisingly modest CUB (mean Effective Number of Codons, ENC = 56), with some exceptions showing stronger codon bias (ENC = 44). Modest codon bias in most studied diatom species may reflect extreme disparity between astronomically large census and modest effective population size (Ne), with fluctuations in population size and linked selection limiting long-term Ne and rendering selection for optimal codons less efficient. For example, genetic diversity (pi ~0.02 at silent sites) in Skeletonema marinoi corresponds to Ne of about 10 million individuals, which is likely many orders of magnitude lower than its census size. Still, Ne ~107 should be large enough to make selection for optimal codons efficient. Thus, we propose that an alternative process-frequent changes of preferred codons, may be a more plausible reason for low CUB despite highly efficient selection for preferred codons in diatom populations. The shifts in the set of optimal codons should result in the changes of the direction of selection for codon usage, so the actual codon usage never catches up with the moving target of the optimal set of codons and the species never develop strong CUB. Indeed, we detected strong shifts in preferential codon usage within some diatom genera, with switches between preferentially GC-rich and AT-rich 3rd codon positions (GC3). For example, GC3 ranges from 0.6 to 1 in most Chaetoceros species, while for Chaetoceros dichaeta GC3 = 0.1. Both variation in selection intensity and mutation spectrum may drive such shifts in codon usage and limit the observed CUB. Our study represents the first genome-wide analysis of CUB in diatoms and the first such analysis for a major phytoplankton group.
| S-EPMC6896221 | biostudies-literature
Project description:Many large national and transnational studies have been dedicated to the analysis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genome, most of which focused on missense and nonsense mutations. However, approximately 30 per cent of the SARS-CoV-2 variants are synonymous, therefore changing the target codon without affecting the corresponding protein sequence. By performing a large-scale analysis of sequencing data generated from almost 400,000 SARS-CoV-2 samples, we show that silent mutations increasing the similarity of viral codons to the human ones tend to fixate in the viral genome overtime. This indicates that SARS-CoV-2 codon usage is adapting to the human host, likely improving its effectiveness in using the human aminoacyl-tRNA set through the accumulation of deceitfully neutral silent mutations. One-Sentence Summary. Synonymous SARS-CoV-2 mutations related to the activity of different mutational processes may positively impact viral evolution by increasing its adaptation to the human codon usage.
| S-EPMC8971538 | biostudies-literature
Project description:From the first emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) till now, multiple mutations that caused synonymous and nonsynonymous substitutions have accumulated. Among them, synonymous substitutions were regarded as "silent" mutations that received less attention than nonsynonymous substitutions that cause amino acid variations. However, the importance of synonymous substitutions can not be neglected. This research focuses on synonymous substitutions on SARS-CoV-2 and proves that synonymous substitutions were under purifying selection in its evolution. The evidence of purifying selection is provided by comparing the mutation number per site in coding and non-coding regions. We then study the two forces of purifying selection: synonymous codon usage and RNA secondary structure. Results show that the codon usage optimization leads to an adapted codon usage towards humans. Furthermore, our results show that the maintenance of RNA secondary structure causes the purifying of synonymous substitutions in the structural region. These results explain the selection pressure on synonymous substitutions during the evolution of SARS-CoV-2.
| S-EPMC9561399 | biostudies-literature