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

  1. Josquin Daron
  2. Ignacio Bravo

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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.

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  1. Version published to 10.3390/v13091800
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    SciScore for 10.1101/2021.01.26.428296: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

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    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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  3. Version published to 10.1101/2021.01.26.428296v1 on bioRxiv