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Rampant C->U hypermutation in the genomes of SARS-CoV-2 and other coronaviruses – causes and consequences for their short and long evolutionary trajectories
Peter Simmonds
Acceso Abierto
Atribución-NoComercial-SinDerivadas
https://doi.org/10.1101/2020.05.01.072330
https://www.biorxiv.org/content/10.1101/2020.05.01.072330v1
The pandemic of SARS coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a dataset of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean 5.5-9.5 nucleotide differences from each other, commensurate with a mid-range coronavirus substitution rate of 3×10−4 substitutions/site/year. Almost half of sequence changes were C->U transitions with an 8-fold base frequency normalised directional asymmetry between C->U and U->C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV and MERS-CoV) and to a decreasing degree in other human coronaviruses (HCoV-NL63, -OC43, -229E and -HKU1) proportionate to their increasing divergence. C->U transitions underpinned almost half of the amino acid differences between SARS-CoV-2 variants, and occurred preferentially in both 5’U/A and 3’U/A flanking sequence contexts comparable to favoured motifs of human APOBEC3 proteins. Marked base asymmetries observed in non-pandemic human coronaviruses (U>>A>G>>C) and low G+C contents may represent long term effects of prolonged C->U hypermutation in their hosts.
bioRxiv
01-05-2020
Preimpreso
Inglés
Público en general
VIRUS RESPIRATORIOS
Versión publicada
publishedVersion - Versión publicada
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