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Abstract
One of the most remarkable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) features is the significant number of mutations they acquired. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we describe a new SARS-CoV-2 P.1 sub-lineage circulating in Brazil, denoted here as Gamma-like-II, that as well as the previously described lineage Gamma-like-I shares several lineage-defining mutations with the VOC Gamma. Reconstructions of ancestor sequences support that most lineage-defining mutations of the Spike (S) protein, including those at the receptor-binding domain (RBD), accumulated at the first P.1 ancestor. In contrast, mutations outside the S protein were mostly fixed at subsequent steps. Our evolutionary analyses estimate that P.1-ancestral strains carrying RBD mutations of concern probably circulated cryptically in the Amazonas for several months before the emergence of the VOC Gamma. Unlike the VOC Gamma, the other P.1 sub-lineages displayed a much more restricted dissemination and accounted for a low fraction (<2 per cent) of SARS-CoV-2 infections in Brazil in 2021. The stepwise diversification of lineage P.1 through multiple inter-host transmissions is consistent with the hypothesis that partial immunity acquired from natural SARS-CoV-2 infections in heavily affected regions might have been a major driving force behind the natural selection of some VOCs. The lag time between the emergence of the P.1 ancestor and the expansion of the VOC Gamma and the divergent epidemic trajectories of P.1 sub-lineages support a complex interplay between the emergence of mutations of concern and viral spread in Brazil.
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1 Plataforma de Vigilância Molecular, Instituto Gonçalo Moniz, Fiocruz , Salvador, Bahia 40296-710, Brazil
2 Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, Fiocruz , Rio de Janeiro 21040-900, Brazil
3 Laboratório de Vírus Respiratórios e do Sarampo (LVRS), Instituto Oswaldo Cruz, Fiocruz , Rio de Janeiro 21040-900, Brazil
4 Laboratório Central de Saúde Pública do Estado do Rio Grande do Sul (LACEN-RS) , Porto Alegre 90610-000, Brazil
5 Laboratório Central de Saúde Pública do Estado de Santa Catarina (LACEN-SC) , Florianópolis 88010-001, Brazil
6 Laboratório Central de Saúde Pública do Estado do Rio de Janeiro (LACEN-RJ) , Rio de Janeiro 20231-000, Brazil
7 Laboratório Central de Saúde Pública do Estado de Alagoas (LACEN-AL) , Maceió 57036-000, Brazil
8 Laboratório Central de Saúde Pública do Estado do Paraná (LACEN-PR) , Curitiba 80045-150, Brazil
9 Laboratório Central de Saúde Pública do Estado de Minas Gerais (LACEN-MG) , Belo Horizonte 30510-010, Brazil
10 Laboratório Central de Saúde Pública do Estado do Espírito Santo (LACEN-ES) , Vitória 29052-121, Brazil
11 Instituto Nacional de Infectologia (INI), Fiocruz , Rio de Janeiro 21040-900, Brazil
12 Laboratório de Ecologia de Doenças Transmissíveis na Amazônia (EDTA), Instituto Leônidas e Maria Deane, FIOCRUZ , Manaus, Amazonas 69027-070, Brazil
13 Fundação de Vigilância em Saúde do Amazonas , Manaus 69093-018, Brazil
14 Laboratório Central de Saúde Pública do Amazonas , Manaus 69020-040, Brazil
15 Departamento de Entomologia, Instituto Aggeu Magalhães, Fiocruz , Recife, Pernambuco 50670-420, Brazil
16 Departamento de Biologia, Centro de Ciências Exatas, Naturais e da Saúde, Universidade Federal do Espírito Santo , Alegre 29500-000, Brazil