Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil

BackgroundP.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfe...

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Main Authors: Ricardo Ariel Zimerman, Patrícia Aline Gröhs Ferrareze, Flavio Adsuara Cadegiani, Carlos Gustavo Wambier, Daniel do Nascimento Fonseca, Andrea Roberto de Souza, Andy Goren, Liane Nanci Rotta, Zhihua Ren, Claudia Elizabeth Thompson
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2022.806611/full
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author Ricardo Ariel Zimerman
Patrícia Aline Gröhs Ferrareze
Flavio Adsuara Cadegiani
Carlos Gustavo Wambier
Daniel do Nascimento Fonseca
Andrea Roberto de Souza
Andy Goren
Liane Nanci Rotta
Zhihua Ren
Claudia Elizabeth Thompson
Claudia Elizabeth Thompson
author_facet Ricardo Ariel Zimerman
Patrícia Aline Gröhs Ferrareze
Flavio Adsuara Cadegiani
Carlos Gustavo Wambier
Daniel do Nascimento Fonseca
Andrea Roberto de Souza
Andy Goren
Liane Nanci Rotta
Zhihua Ren
Claudia Elizabeth Thompson
Claudia Elizabeth Thompson
author_sort Ricardo Ariel Zimerman
collection DOAJ
description BackgroundP.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies.MethodsThe samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples.ResultsForty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage.ConclusionP.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.
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spelling doaj.art-917a647aa2484b0fa3672c0198a9d54b2022-12-21T17:24:38ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-02-01910.3389/fmed.2022.806611806611Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, BrazilRicardo Ariel Zimerman0Patrícia Aline Gröhs Ferrareze1Flavio Adsuara Cadegiani2Carlos Gustavo Wambier3Daniel do Nascimento Fonseca4Andrea Roberto de Souza5Andy Goren6Liane Nanci Rotta7Zhihua Ren8Claudia Elizabeth Thompson9Claudia Elizabeth Thompson10Hospital da Brigada Militar, Porto Alegre, BrazilGraduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, BrazilCorpometria Institute, Brasília, BrazilDepartment of Dermatology, Warren Alpert Medical School of Brown University, Providence, RI, United StatesSamel and Oscar Nicolau Hospitals, Manaus, BrazilSamel and Oscar Nicolau Hospitals, Manaus, BrazilApplied Biology, Inc., Irvine, CA, United StatesGraduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, BrazilSuzhou Kintor Pharmaceutical, Inc., Suzhou, ChinaGraduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, BrazilDepartment of Pharmacosciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, BrazilBackgroundP.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies.MethodsThe samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples.ResultsForty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage.ConclusionP.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.https://www.frontiersin.org/articles/10.3389/fmed.2022.806611/fullCOVID-19SARS-CoV-2P.1VOCgenomic epidemiologyphylogenomics
spellingShingle Ricardo Ariel Zimerman
Patrícia Aline Gröhs Ferrareze
Flavio Adsuara Cadegiani
Carlos Gustavo Wambier
Daniel do Nascimento Fonseca
Andrea Roberto de Souza
Andy Goren
Liane Nanci Rotta
Zhihua Ren
Claudia Elizabeth Thompson
Claudia Elizabeth Thompson
Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil
Frontiers in Medicine
COVID-19
SARS-CoV-2
P.1
VOC
genomic epidemiology
phylogenomics
title Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil
title_full Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil
title_fullStr Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil
title_full_unstemmed Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil
title_short Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil
title_sort comparative genomics and characterization of sars cov 2 p 1 gamma variant of concern from amazonas brazil
topic COVID-19
SARS-CoV-2
P.1
VOC
genomic epidemiology
phylogenomics
url https://www.frontiersin.org/articles/10.3389/fmed.2022.806611/full
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