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Title

SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations

AuthorsMartínez-González, Brenda; Soria, María Eugenia; Vázquez-Sirvent, Lucía; Ferrer-Orta, Cristina CSIC ; Lobo-Vega, Rebeca; Mínguez, Pablo; Fuente, Lorena de la; Llorens, Carlos; Soriano, Beatriz; Ramos-Ruiz, Ricardo; Cortón, Marta; López-Rodríguez, Rosario; García-Crespo, Carlos; Somovilla, Pilar; Durán-Pastor, Antoni; Gallego, Isabel CSIC ORCID; Ávila, Ana Isabel de; Delgado, Soledad; Morán, Federico; López-Galíndez, Cecilio; Gómez, Jordi; Enjuanes Sánchez, Luis CSIC ORCID ; Salar-Vidal, Llanos; Esteban-Muñoz, Mario; Esteban, Jaime; Fernández-Roblas, Ricardo; Gadea, Ignacio; Ayuso, Carmen; Ruíz-Hornillos, Javier; Verdaguer, Núria CSIC ORCID ; Domingo, Esteban CSIC ORCID; Perales, Celia CSIC ORCID
KeywordsRNA virus
COVID-19
Ultra-deep sequencing
viral quasispecies;
Mutation
Deletion
nsp12 (polymerase)
Spike
Issue Date8-Jun-2022
PublisherMolecular Diversity Preservation International
CitationPathogens 11(6): 662 (2022)
AbstractPopulations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed.
Publisher version (URL)https://doi.org/10.3390/pathogens11060662
URIhttp://hdl.handle.net/10261/280480
DOI10.3390/pathogens11060662
E-ISSN2076-0817
Appears in Collections:(VICYT) Colección Especial COVID-19
(CNB) Artículos
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(IBMB) Artículos




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