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.
Highlights
IntroductionThe Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of respiratory disease COVID-19, occasionally leading to acute respiratory distress syndrome and eventually death [1]
To better understand the causes of codon usage bias (CUB) differences between CoVs, we investigated a total of 82 complete CoVs genomes
SARS-CoV-2 is the third Coronavirinae zoonotic spillover of the 21-century, and the associated COVID-19 poses an unprecedented burden on human public health
Summary
The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of respiratory disease COVID-19, occasionally leading to acute respiratory distress syndrome and eventually death [1]. With no antiviral drugs nor vaccines initially available, and with the presence of asymptomatic carriers, the COVID-19 outbreak turned into a public health emergency of international concern. Before the 2019 zoonotic spillover, viruses closely related to SARS-CoV-2 had circulated probably for decades in bats as well as in other intermediate hosts, such as the Sunda pangolin Manis javanica [2]. All CoVs are likely linked to zoonotic events, mostly from bats or rodents, with occasionally domestic animals playing the role of intermediate hosts [7]. Given the high zoonotic potential of the Orthocoronavirinae [8,9] and the vast repertoire of mammalian and avian hosts they infect, there is an urgent need to evaluate the potential zoonotic risk for each individual
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