The substitution spectra of coronavirus genomes

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has triggered an unprecedented international effort to sequence complete viral genomes. We leveraged this wealth of information to characterize the substitution spectrum of SARS-CoV-2 and to compare it with those of other human and animal coronaviruses. We show that, once nucleotide composition is taken into account, human and most animal coronaviruses display a mutation spectrum dominated by C to U and G to U substitutions, a feature that is not shared by other positive-sense RNA viruses. However, the proportions of C to U and G to U substitutions tend to decrease as divergence increases, suggesting that, whatever their origin, a proportion of these changes is subsequently eliminated by purifying selection. Analysis of the sequence context of C to U substitutions showed little evidence of apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-mediated editing and such contexts were similar for SARS-CoV-2 and Middle East respiratory syndrome coronavirus sampled from different hosts, despite different repertoires of APOBEC3 proteins in distinct species. Conversely, we found evidence that C to U and G to U changes affect CpG dinucleotides at a frequency higher than expected. Whereas this suggests ongoing selective reduction of CpGs, this effect alone cannot account for the substitution spectra. Finally, we show that, during the first months of SARS-CoV-2 pandemic spread, the frequency of both G to U and C to U substitutions increased. Our data suggest that the substitution spectrum of SARS-CoV-2 is determined by an interplay of factors, including intrinsic biases of the replication process, avoidance of CpG dinucleotides and other constraints exerted by the new host.

Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic

“…4b ) and to distinguish chronic infections from re-infections. In addition, phylogenetic assumptions regarding the distribution and independence of mutations can be violated by virus mutational patterns related to host antiviral defences 85 (Fig. 4c ).…”

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: a prospective observational cohort study

“…Viruses mutate over time 1 , affecting transmissibility 2 , disease presentation 3 , and natural or vaccine-induced protective immunity. 4 The Delta variant of SARS-CoV-2 (B.1.617.2) was identified in India in late 2020 and declared a ‘Variant of Concern’ in May 2021 by the UK 5 , the World Health Organization 6 , and the European Centre for Disease Control 7 , mainly due to evidence of increased transmissibility, 8 , 9 possibly larger risk of hospitalisation, 10 , 11 and conceivably less effectiveness of vaccination compared with previous variants 4 , 12 , 13 .…”

Discovery of a Novel Coronavirus in Swedish Bank Voles (Myodes glareolus)

“…The genomes of strains Grimso215 and Grimso2306 shared 95.6% sequence identity at the nucleotide level, with 1338 site differences. This divergence is notably higher than the expected differences based on a typical substitution rate for coronaviruses of 0.001 substitutions per site per year [16,17], which under Poisson distribution predicts an accumulation of 61-121 substitutions over three years. This observation suggests that either multiple strains of Grimso-like viruses are co-circulating in bank voles in Grimsö or that these viruses are transmitted regularly to bank voles from other species.…”