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Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of previously unreported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: (i) the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution, and (ii) a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains.<\/jats:p>","DOI":"10.1371\/journal.pone.0268389","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T13:31:26Z","timestamp":1653399086000},"page":"e0268389","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution"],"prefix":"10.1371","volume":"17","author":[{"given":"Danilo Rosa","family":"Nunes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Torres","family":"Braconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa F.","family":"Ludwig-Begall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarice Weis","family":"Arns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-7601","authenticated-orcid":true,"given":"Ricardo","family":"Dur\u00e3es-Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"pone.0268389.ref001","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1126\/science.1087139","article-title":"Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China","volume":"302","author":"Y Guan","year":"2003","journal-title":"Science"},{"key":"pone.0268389.ref002","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1056\/NEJMoa1211721","article-title":"Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia","volume":"367","author":"AM Zaki","year":"2012","journal-title":"N Engl J Med"},{"key":"pone.0268389.ref003","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00705-020-04628-0","article-title":"The emergence of SARS, MERS and novel SARS-2 coronaviruses in the 21st century","volume":"165","author":"Moreli ML Costa VG da","year":"2020","journal-title":"Arch Virol"},{"key":"pone.0268389.ref004","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/bs.aivir.2018.01.001","article-title":"Hosts and Sources of Endemic Human Coronaviruses","volume":"100","author":"VM Corman","year":"2018","journal-title":"Adv Virus Res"},{"key":"pone.0268389.ref005","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/s41564-020-0771-4","article-title":"Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic","volume":"5","author":"MF Boni","year":"2020","journal-title":"Nat Microbiol"},{"key":"pone.0268389.ref006","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: implications for SARS-CoV-2","volume":"19","author":"P V\u2019kovski","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"pone.0268389.ref007","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/s41591-021-01472-w","article-title":"The next phase of SARS-CoV-2 surveillance: real-time molecular epidemiology","volume":"27","author":"BBO Munnink","year":"2021","journal-title":"Nat Med"},{"key":"pone.0268389.ref008","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1093\/molbev\/msn123","article-title":"A maximum likelihood method for detecting directional evolution in protein sequences and its application to influenza A virus","volume":"25","author":"SLK Pond","year":"2008","journal-title":"Mol Biol Evol"},{"key":"pone.0268389.ref009","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41467-020-20688-x","article-title":"Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy","volume":"12","author":"C Alteri","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0268389.ref010","unstructured":"Centers for Disease Control and Prevention (CDC). SARS-CoV-2 Variant Classifications and Definitions. 01 December 2021. 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Spread of SARS-CoV-2 at One of the Largest Metropolitan Areas of Northeast Brazil","volume":"12","author":"MHS Paiva","year":"2020","journal-title":"Viruses"},{"key":"pone.0268389.ref038","doi-asserted-by":"crossref","first-page":"2000305","DOI":"10.2807\/1560-7917.ES.2020.25.13.2000305","article-title":"Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe","volume":"25","author":"P Stefanelli","year":"2020","journal-title":"Eurosurveill"},{"key":"pone.0268389.ref039","doi-asserted-by":"crossref","first-page":"e00119","DOI":"10.1128\/JVI.00119-21","article-title":"Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil","volume":"95","author":"CM Voloch","year":"2021","journal-title":"J Virol"},{"key":"pone.0268389.ref040","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1126\/science.abh2644","article-title":"Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil","volume":"372","author":"NR Faria","year":"2021","journal-title":"Science"},{"key":"pone.0268389.ref041","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3390\/v13050724","article-title":"A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil","volume":"13","author":"PC Resende","year":"2021","journal-title":"Viruses"},{"key":"pone.0268389.ref042","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/S0140-6736(21)00183-5","article-title":"Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence","volume":"397","author":"EC Sabino","year":"2021","journal-title":"Lancet"},{"key":"pone.0268389.ref043","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1126\/science.abi7994","article-title":"SARS-CoV-2 immune evasion by the B.1.427\/B.1.429 variant of concern","volume":"373","author":"M McCallum","year":"2021","journal-title":"Science"},{"key":"pone.0268389.ref044","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.chom.2021.02.003","article-title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","volume":"29","author":"AJ Greaney","year":"2021","journal-title":"Cell Host Microbe"},{"key":"pone.0268389.ref045","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","article-title":"SARS-CoV-2 variants, spike mutations and immune escape","volume":"19","author":"WT Harvey","year":"2021","journal-title":"Nat Rev 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