Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution.
[en] Nearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. 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.
Disciplines :
Veterinary medicine & animal health Immunology & infectious disease
Author, co-author :
Nunes, Danilo Rosa; Department of Microbiology, Immunology and Parasitology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
Braconi, Carla Torres; Department of Microbiology, Immunology and Parasitology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
Ludwig-Begall, Louisa ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Arns, Clarice Weis; Laboratory of Virology, University of Campinas, Campinas, SP, Brazil
Durães-Carvalho, Ricardo ; Department of Microbiology, Immunology and Parasitology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
Language :
English
Title :
Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution.
FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico CAPES - Coordenação de Aperfeicoamento de Pessoal de Nível Superior
Funding text :
Funding:Thisworkwassupportedbythe Fundac ¸ãodeAmparoàPesquisadoEstado384de SãoPaulo(FAPESP),Brazil,grants2019/01255-9 and2021/03684-4(Young385Investigator Program)(RD-C),andbytheConselhoNacionalde Desenvolvimento386 Cientı ´ fico e Tecnolo ´ gico (CNPq),Brazil,grant405691/2018-1(C.T.B).DRNis387recipientofaninstitutionalscholarship fromtheCoordenac ¸ãodeAperfeic ¸oamento388de Pessoal de Nı ´vel Superior(CAPES),Brazil,grant 88887.506234/2020-00.This work was supported by the Fundação de Amparo à Pesquisa doEstado384 de São Paulo (FAPESP), Brazil, grants 2019/01255-9 and 2021/03684-4(Young385 Investigator Program) (RD-C), and by the Conselho Nacional de Desenvolvimento386 Científico e Tecnológico (CNPq), Brazil, grant 405691/2018-1 (C.T.B). DRNis387 recipient of an institutional scholarship from the Coordenação de Aperfeiçoamento388 de Pessoal de Nível Superior (CAPES), Brazil, grant 88887.506234/2020-00. We gratefully acknowledge the authors and both the originating and submitting laboratories for the sequence data in GISAID EpiCoV and GenBank on which this work is based. The authors also thank the Rede Corona-Ômica/MCTI/FINEP, the National Laboratory for Scientific Computing (LNCC/MCTI, Brazil) for providing HPC resources of the Santos Dumont supercomputer (ID #45691), and Prof. Luiz Mário Ramos Janini for fruitful discussion.
Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL, et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science. 2003; 302: 276–8. https://doi.org/10.1126/science.1087139 PMID: 12958366
Zaki AM, Boheemen S van, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012; 367: 1814–20. https://doi.org/10.1056/NEJMoa1211721 PMID: 23075143
Costa VG da Moreli ML, Saivish MV. The emergence of SARS, MERS and novel SARS-2 coronaviruses in the 21st century. Arch Virol. 2020; 165: 1517–26. https://doi.org/10.1007/s00705-020-04628-0 PMID: 32322993
Corman VM, Muth D, Niemeyer D, Drosten C. Hosts and Sources of Endemic Human Coronaviruses. Adv Virus Res. 2018; 100: 163–88. https://doi.org/10.1016/bs.aivir.2018.01.001 PMID: 29551135
Boni MF, Lemey P, Jiang X, Lam TT-Y, Perry BW, Castoe TA, et al. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Nat Microbiol. 2020; 5: 1408–17. https://doi.org/10.1038/s41564-020-0771-4 PMID: 32724171
V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021: 19: 155–70. https://doi.org/10.1038/s41579-020-00468-6 PMID: 33116300
Munnink BBO, Worp N, Nieuwenhuijse DF, Sikkema RS, Haagmans B, Fouchier RAM, et al. The next phase of SARS-CoV-2 surveillance: real-time molecular epidemiology. Nat Med. 2021; 27: 1518–24. https://doi.org/10.1038/s41591-021-01472-w PMID: 34504335
Pond SLK, Poon AFY, Brown AJL, Frost SDW. A maximum likelihood method for detecting directional evolution in protein sequences and its application to influenza A virus. Mol Biol Evol. 2008; 25: 1809–24. https://doi.org/10.1093/molbev/msn123 PMID: 18511426
Alteri C, Cento V, Piralla A, Costabile V, Tallarita M, Colagrossi L, et al. Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy. Nat Commun. 2021; 12: 434. https://doi.org/10.1038/s41467-020-20688-x PMID: 33469026
Centers for Disease Control and Prevention (CDC). SARS-CoV-2 Variant Classifications and Definitions. 01 December 2021. Available at: https://www.cdc.gov/coronavirus/2019-ncov/variants/variantinfo.html.
Peacock TP, Penrice-Randal R, Hiscox JA, Barclay WS. SARS-CoV-2 one year on: evidence for ongoing viral adaptation. J Gen Virol. 2021; 102: 001584. https://doi.org/10.1099/jgv.0.001584 PMID: 33855951
Durães-Carvalho R, Ludwig-Begall LF, Salemi M, Lins RD, Marques ETA. Influence of directional positive Darwinian selection-driven evolution on arboviruses Dengue and Zika virulence and pathogenesis. Mol Phylogenet Evol. 2019; 140: 106607. https://doi.org/10.1016/j.ympev.2019.106607 PMID: 31473337
Okonechnikov K, Golosova O, Fursov M. Unipro UGENE: a unified bioinformatics toolkit. Bioinformatics. 2012; 28: 1166–7. https://doi.org/10.1093/bioinformatics/bts091 PMID: 22368248
Prosperi MCF, Ciccozzi M, Fanti I, Saladini F, Pecorari M, Borghi V, et al. A novel methodology for large-scale phylogeny partition. Nature Commun. 2011; 2: 321. https://doi.org/10.1038/ncomms1325 PMID: 21610724
Price MN, Dehal PS, Arkin AP. FastTree 2—approximately maximum-likelihood trees for large alignments. PLoS One. 2010; 5: e9490. https://doi.org/10.1371/journal.pone.0009490 PMID: 20224823
Lai MMC. Genetic Recombination in RNA Viruses. Curr Top Microbiol Immunol. 1992; 176: 21–32. https://doi.org/10.1007/978-3-642-77011-1_2 PMID: 1600753
Lemey P, Salemi M, Vandamme A-M. The Phylogenetic Handbook: A Practical Approach to Phylogenetic Analysis and Hypothesis Testing. 2nd ed. Cambridge University Press; 2009.
Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016; 24: 490–502. https://doi.org/10.1016/j.tim.2016.03. 003 PMID: 27012512
Pollett S, Conte MA, Sanborn M, Jarman RG, Lidl GM, Modjarrad K, et al. A comparative recombination analysis of human coronaviruses and implications for the SARS-CoV-2 pandemic. Sci Rep. 2021; 11: 17365. https://doi.org/10.1038/s41598-021-96626-8 PMID: 34462471
He Y, Ma W, Dang S, Chen L, Zhang R, Mei S, et al. Possible recombination between two variants of concern in a COVID-19 patient. Emerg Microbes Infect. 2022; 11: 552–55. https://doi.org/10.1080/22221751.2022.2032375 PMID: 35081877
Forni D, Cagliani R, Arrigoni F, Benvenuti M, Mozzi A, Pozzoli U, et al. Adaptation of the endemic coronaviruses HCoV-OC43 and HCoV-229E to the human host. Virus Evol. 2021; 7: veab061. https://doi.org/10.1093/ve/veab061 PMID: 34527284
Muth D, Corman VM, Roth H, Binger T, Dijkman R, Gottula LT, et al. Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission. Sci Rep. 2018; 8: 15177. https://doi.org/10.1038/s41598-018-33487-8 PMID: 30310104
Pereira F. Evolutionary dynamics of the SARS-CoV-2 ORF8 accessory gene. Infect Genet Evol. 2020; 85: 104525. https://doi.org/10.1016/j.meegid.2020.104525 PMID: 32890763
Pereira F. SARS-CoV-2 variants lacking a functional ORF8 may reduce accuracy of serological testing. J Immunol Methods. 2021; 488: 112906. https://doi.org/10.1016/j.jim.2020.112906 PMID: 33137303
Dearlove B, Lewitus E, Bai H, Li Y, Reeves DB, Joyce MG, et al. A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants. Proc Natl Acad Sci USA. 2020; 117: 23652–62. https://doi.org/10.1073/pnas.2008281117 PMID: 32868447
MacLean OA, Lytras S, Weaver S, Singer JB, Boni MF, Lemey P, et al. Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen. PLoS Biol. 2021; 19: e3001115. https://doi.org/10.1371/journal.pbio.3001115 PMID: 33711012
Martin DP, Weaver S, Tegally H, San JE, Shank SD, Wilkinson E, et al. The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape. Cell. 2021;5189–5200.e7. https://doi.org/10.1016/j.cell.2021.09.003 PMID: 34537136
Yadav PD, Potdar VA, Choudhary ML, Nyayanit DA, Agrawal M, Jadhav SM, et al. Full-genome sequences of the first two SARS-CoV-2 viruses from India. Indian J Med Res. 2020; 151: 200–09. https://doi.org/10.4103/ijmr.IJMR_663_20 PMID: 32242873
Hodcroft EB, Zuber M, Nadeau S, Vaughan TG, Crawford KHD, Althaus CL, et al. Spread of a SARS-CoV-2 variant through Europe in the summer of 2020. Nature. 2021; 595: 707–12. https://doi.org/10.1038/s41586-021-03677-y PMID: 34098568
Velazquez-Salinas L, Zarate S, Eberl S, Gladue DP, Novella I, Borca MV. Positive Selection of ORF1ab, ORF3a, and ORF8 Genes Drives the Early Evolutionary Trends of SARS-CoV-2 During the 2020 COVID-19 Pandemic. Front Microbiol. 2020; 11: 550674. https://doi.org/10.3389/fmicb.2020. 550674 PMID: 33193132
Zhang L, Jackson CB, Mou H, Ojha A, Peng H, Quinlan BD, et al. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat Commun. 2020; 11: 6013. https://doi.org/10.1038/s41467-020-19808-4 PMID: 33243994
Plante JA, Liu Y, Liu J, Xia H, Johnson BA, Lokugamage KG, et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature. 2021; 592: 116–21. https://doi.org/10.1038/s41586-020-2895-3 PMID: 33106671
Candido DS, Claro IM, de Jesus JG, Souza WM, Moreira FRR, Dellicour S, et al. Evolution and epidemic spread of SARS-CoV-2 in Brazil. Science. 2020; 369: 1255–60. https://doi.org/10.1126/science. abd2161 PMID: 32703910
Paiva MHS, Guedes DRD, Docena C, Bezerra MF, Dezordi FZ, Machado LC, et al. Multiple Introductions Followed by Ongoing Community Spread of SARS-CoV-2 at One of the Largest Metropolitan Areas of Northeast Brazil. Viruses. 2020; 12: 1414. https://doi.org/10.3390/v12121414 PMID: 33316947
Stefanelli P, Faggioni G, Presti AL, Fiore S, Marchi A, Benedetti E, et al. 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. Eurosurveill. 2020; 25: 2000305. https://doi.org/10.2807/1560-7917.ES.2020.25.13.2000305 PMID: 32265007
Voloch CM, da Silva Francisco R Jr, Almeida LGP de, Cardoso CC, Brustolini OJ, Gerber AL, et al. Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil. J Virol. 2021; 95: e00119–21. https://doi.org/10.1128/JVI.00119-21 PMID: 33649194
Faria NR, Mellan TA, Whittaker C, Claro IM, Candido D da S, Mishra S, et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science. 2021; 372: 815–21. https://doi.org/10.1126/science.abh2644 PMID: 33853970
Resende PC, Gräf T, Paixão ACD, Appolinario L, Lopes RS, Mendonça AC da F, et al. 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. Viruses. 2021; 13: 724. https://doi.org/10.3390/v13050724 PMID: 33919314
Sabino EC, Buss LF, Carvalho MPS, Prete CA, Crispim MAE, Fraiji NA, et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet. 2021; 397: 452–5. https://doi.org/10.1016/ S0140-6736(21)00183-5 PMID: 33515491
McCallum M, Bassi J, Marco AD, Chen A, Walls AC, Iulio JD, et al. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science. 2021; 373: 648–54. https://doi.org/10.1126/science. abi7994 PMID: 34210893
Greaney AJ, Loes AN, Crawford KHD, Starr TN, Malone KD, Chu HY, et al. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe. 2021; 29: 463–76. https://doi.org/10.1016/j.chom.2021.02.003 PMID: 33592168
Harvey WT, Carabelli AM, Jackson B, Gupta RK, Thomson EC, Harrison EM, et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol. 2021; 19: 409–24. https://doi.org/10.1038/s41579-021-00573-0 PMID: 34075212
Haddad D, John SE, Mohammad A, Hammad MM, Hebbar P, Channanath A, et al. SARS-CoV-2: Possible recombination and emergence of potentially more virulent strains. PLoS One. 2021; 16: e0251368. https://doi.org/10.1371/journal.pone.0251368 PMID: 34033650
Centers for Disease Control and Prevention (CDC). What You Need to Know About Variants. 02 February 2022. Available at: https://www.cdc.gov/coronavirus/2019-ncov/variants/delta-variant.html.
Kirola L. Genetic emergence of B.1.617.2 in COVID-19. New Microbes New Infect. 2021; 43: 100929. https://doi.org/10.1016/j.nmni.2021.100929 PMID: 34336227
McCallum M, Walls AC, Sprouse KR, Bowen JE, Rosen L, Dang HV, et al. Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants. Science. 2021; 374: 1621–26 https://doi.org/10.1126/science.abl8506 PMID: 34751595
Lamarca AP, Almeida LGP de, da Silva Francisco R Jr, Cavalcante L, Machado DT, Brustolini O, et al. Genomic surveillance tracks the first communitary outbreak of Delta (B.1.617.2) variant in Brazil. J Virol. 2022; 96: e0122821.2021
Pan American Health Organization (PAHO). Epidemiological Update: Increase of the Delta variant and its potential impact in the Region of the Americas. 8 August 2021. Available at: https://www.paho.org/en/documents/epidemiological-update-increase-delta-variant-and-its-potential-impact-regionamericas-8.
Centers for Disease Control and Prevention (CDC). COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence—25 U.S. Jurisdictions, April 4–December 25, 2021. 28 January 2022. Available at: https://www.cdc.gov/mmwr/volumes/71/wr/mm7104e2.htm.
U.S. Food & Drug Administration (FDA). Spikevax and Moderna COVID-19 Vaccine. 31 January 2022. Available at https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019covid-19/moderna-covid-19-vaccine.
Pegu A, O’Connell S, Schmidt SD, O’Dell S, Talana CA, Lai L, et al. Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants. Science. 2021; 373: 1372–77. https://doi.org/10.1126/science.abj4176 PMID: 34385356
Li X-N, Huang Y, Wang W, Jing Q-L, Zhang C-H, Qin P-Z, et al. Effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant infection in Guangzhou: a test-negative case-control real-world study. Emerg Microbes Infect. 2021; 10: 1751–59. https://doi.org/10.1080/22221751.2021. 1969291 PMID: 34396940
Bernal JL, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. New Engl J Med. 2021; 385: 585–94. https://doi.org/10.1056/NEJMoa2108891 PMID: 34289274
Andreata-Santos R, Janini LMR, Durães-Carvalho R. From Alpha to Omicron SARS-CoV-2 variants: What their evolutionary signatures can tell us? J Med Virol. 2022. Online ahead of print. https://doi.org/10.1002/jmv.27555 PMID: 34978091
Humphrey W, Dalke A, Schulten K. VMD—Visual Molecular Dynamics. J Mol Graph. 1996; 14: 33–8. https://doi.org/10.1016/0263-7855(96)00018-5 PMID: 8744570