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Variability in Codon Usage in Coronaviruses Is Mainly Driven by Mutational Bias and Selective Constraints on CpG Dinucleotide.

ABSTRACT: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human-emerged virus of the 21st century from the Coronaviridae family, causing the ongoing coronavirus disease 2019 (COVID-19) pandemic. Due to the high zoonotic potential of coronaviruses, it is critical to unravel their evolutionary history of host species breadth, host-switch potential, adaptation and emergence, to identify viruses posing a pandemic risk in humans. We present here a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses, is only weakly dependent on their primary host, and is dominated by mutational bias towards AU-enrichment and by CpG avoidance. Indeed, variation in GC3 explains around 34%, while variation in CpG frequency explains around 14% of total variation in codon usage bias. Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception being the three recently infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that, while replicating in humans, SARS-CoV-2 is slowly becoming AU-richer, likely until attaining a new mutational equilibrium.

SUBMITTER: Daron J

PROVIDER: S-EPMC8473333 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The prevailing COVID-19 pandemic has drawn the attention of the scientific community to study the evolutionary origin of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). This study is a comprehensive quantitative analysis of the protein-coding sequences of seven human coronaviruses (HCoVs) to decipher the nucleotide sequence variability and codon usage patterns. It is essential to understand the survival ability of the viruses, their adaptation to hosts, and their evolution. The current analysis revealed a high abundance of the relative dinucleotide (odds ratio), GC and CT pairs in the first and last two codon positions, respectively, as well as a low abundance of the CG pair in the last two positions of the codon, which might be related to the evolution of the viruses. A remarkable level of variability of GC content in the third position of the codon among the seven coronaviruses was observed. Codons with high RSCU values are primarily from the aliphatic and hydroxyl amino acid groups, and codons with low RSCU values belong to the aliphatic, cyclic, positively charged, and sulfur-containing amino acid groups. In order to elucidate the evolutionary processes of the seven coronaviruses, a phylogenetic tree (dendrogram) was constructed based on the RSCU scores of the codons. The severe and mild categories CoVs were positioned in different clades. A comparative phylogenetic study with other coronaviruses depicted that SARS-CoV-2 is close to the CoV isolated from pangolins (Manis javanica, Pangolin-CoV) and cats (Felis catus, SARS(r)-CoV). Further analysis of the effective number of codon (ENC) usage bias showed a relatively higher bias for SARS-CoV and MERS-CoV compared to SARS-CoV-2. The ENC plot against GC3 suggested that the mutational bias might have a role in determining the codon usage variation among candidate viruses. A codon adaptability study on a few human host parasites (from different kingdoms), including CoVs, showed a diverse adaptability pattern. SARS-CoV-2 and SARS-CoV exhibit relatively lower but similar codon adaptability compared to MERS-CoV.

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Variability in Codon Usage in Coronaviruses Is Mainly Driven by Mutational Bias and Selective Constraints on CpG Dinucleotide.

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