The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape. Martin, D. P, Weaver, S., Tegally, H., San, E. J., Shank, S. D, Wilkinson, E., Giandhari, J., Naidoo, S., Pillay, Y., Singh, L., Lessells, R. J, Gupta, R. K, Wertheim, J. O, Nekturenko, A., Murrell, B., Harkins, G. W, Lemey, P., MacLean, O., Robertson, D. L, de Oliveira, T., & Pond, S. L K. medRxiv, Cold Spring Harbor Laboratory Press, jul, 2021. Paper doi abstract bibtex The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition. ### Competing Interest Statement JOW has received funding from Gilead Sciences, LLC (completed) and the CDC (ongoing) via grants and contracts to his institution unrelated to this research. ### Funding Statement DPM is funded by the Wellcome Trust (222574/Z/21/Z) SLKP was supported by the following grants from the U.S. National Institutes of Health R01 AI134384 (NIH/NIAID), R01 AI140970 (NIH/NIAID), and a RAPID award from the US National Science Foundation 2027196 (NSF/DBI,BIO). DLR is funded by the Medical Research Council (MC$\$_UU$\$_1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. PL acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the EU grant 874850 MOOD and the Wellcome Trust through project 206298/Z/17/Z. JOW was supported by an NIH-NIAID R01 AI135992. SEJ and HT are supported by H3ABioNet, an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) funded by the National Human Genome Research Institute of the National Institutes of Health under Award Number U24HG006941. The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. GWH is supported by a grant from the US National Institutes of Health (1U01Al152151-01) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No human or animal specimens were used and no ethical clearance was required by the University of Cape Town where the PI of this study was based. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All Data used was obtained from GISAID (which is credited in the manuscript)
@article{Martin2021,
abstract = {The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition. {\#}{\#}{\#} Competing Interest Statement JOW has received funding from Gilead Sciences, LLC (completed) and the CDC (ongoing) via grants and contracts to his institution unrelated to this research. {\#}{\#}{\#} Funding Statement DPM is funded by the Wellcome Trust (222574/Z/21/Z) SLKP was supported by the following grants from the U.S. National Institutes of Health R01 AI134384 (NIH/NIAID), R01 AI140970 (NIH/NIAID), and a RAPID award from the US National Science Foundation 2027196 (NSF/DBI,BIO). DLR is funded by the Medical Research Council (MC$\backslash${\_}UU$\backslash${\_}1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research {\&} Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. PL acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the EU grant 874850 MOOD and the Wellcome Trust through project 206298/Z/17/Z. JOW was supported by an NIH-NIAID R01 AI135992. SEJ and HT are supported by H3ABioNet, an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) funded by the National Human Genome Research Institute of the National Institutes of Health under Award Number U24HG006941. The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. GWH is supported by a grant from the US National Institutes of Health (1U01Al152151-01) {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No human or animal specimens were used and no ethical clearance was required by the University of Cape Town where the PI of this study was based. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All Data used was obtained from GISAID (which is credited in the manuscript)},
author = {Martin, Darren P and Weaver, Steven and Tegally, Houryiah and San, Emmanuel James and Shank, Stephen D and Wilkinson, Eduan and Giandhari, Jennifer and Naidoo, Sureshnee and Pillay, Yeshnee and Singh, Lavanya and Lessells, Richard J and Gupta, Ravindra K and Wertheim, Joel O and Nekturenko, Anton and Murrell, Ben and Harkins, Gordon W and Lemey, Philippe and MacLean, Oscar and Robertson, David L and de Oliveira, Tulio and Pond, Sergei L Kosakovsky},
doi = {10.1101/2021.02.23.21252268},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Martin et al. - 2021 - The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the S.pdf:pdf},
journal = {medRxiv},
keywords = {OA,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,genomics{\_}fund{\_}ack,original},
month = {jul},
pages = {2021.02.23.21252268},
pmid = {33688681},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape}},
url = {https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3 https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3.abstract},
year = {2021}
}
Downloads: 0
{"_id":"tw8icpKHPBdZRwazs","bibbaseid":"martin-weaver-tegally-san-shank-wilkinson-giandhari-naidoo-etal-theemergenceandongoingconvergentevolutionofthen501ylineagescoincideswithamajorglobalshiftinthesarscov2selectivelandscape-2021","author_short":["Martin, D. P","Weaver, S.","Tegally, H.","San, E. J.","Shank, S. D","Wilkinson, E.","Giandhari, J.","Naidoo, S.","Pillay, Y.","Singh, L.","Lessells, R. J","Gupta, R. K","Wertheim, J. O","Nekturenko, A.","Murrell, B.","Harkins, G. W","Lemey, P.","MacLean, O.","Robertson, D. L","de Oliveira, T.","Pond, S. L K."],"bibdata":{"bibtype":"article","type":"article","abstract":"The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition. ### Competing Interest Statement JOW has received funding from Gilead Sciences, LLC (completed) and the CDC (ongoing) via grants and contracts to his institution unrelated to this research. ### Funding Statement DPM is funded by the Wellcome Trust (222574/Z/21/Z) SLKP was supported by the following grants from the U.S. National Institutes of Health R01 AI134384 (NIH/NIAID), R01 AI140970 (NIH/NIAID), and a RAPID award from the US National Science Foundation 2027196 (NSF/DBI,BIO). DLR is funded by the Medical Research Council (MC$\\$_UU$\\$_1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. PL acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the EU grant 874850 MOOD and the Wellcome Trust through project 206298/Z/17/Z. JOW was supported by an NIH-NIAID R01 AI135992. SEJ and HT are supported by H3ABioNet, an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) funded by the National Human Genome Research Institute of the National Institutes of Health under Award Number U24HG006941. The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. GWH is supported by a grant from the US National Institutes of Health (1U01Al152151-01) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No human or animal specimens were used and no ethical clearance was required by the University of Cape Town where the PI of this study was based. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All Data used was obtained from GISAID (which is credited in the manuscript)","author":[{"propositions":[],"lastnames":["Martin"],"firstnames":["Darren","P"],"suffixes":[]},{"propositions":[],"lastnames":["Weaver"],"firstnames":["Steven"],"suffixes":[]},{"propositions":[],"lastnames":["Tegally"],"firstnames":["Houryiah"],"suffixes":[]},{"propositions":[],"lastnames":["San"],"firstnames":["Emmanuel","James"],"suffixes":[]},{"propositions":[],"lastnames":["Shank"],"firstnames":["Stephen","D"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Eduan"],"suffixes":[]},{"propositions":[],"lastnames":["Giandhari"],"firstnames":["Jennifer"],"suffixes":[]},{"propositions":[],"lastnames":["Naidoo"],"firstnames":["Sureshnee"],"suffixes":[]},{"propositions":[],"lastnames":["Pillay"],"firstnames":["Yeshnee"],"suffixes":[]},{"propositions":[],"lastnames":["Singh"],"firstnames":["Lavanya"],"suffixes":[]},{"propositions":[],"lastnames":["Lessells"],"firstnames":["Richard","J"],"suffixes":[]},{"propositions":[],"lastnames":["Gupta"],"firstnames":["Ravindra","K"],"suffixes":[]},{"propositions":[],"lastnames":["Wertheim"],"firstnames":["Joel","O"],"suffixes":[]},{"propositions":[],"lastnames":["Nekturenko"],"firstnames":["Anton"],"suffixes":[]},{"propositions":[],"lastnames":["Murrell"],"firstnames":["Ben"],"suffixes":[]},{"propositions":[],"lastnames":["Harkins"],"firstnames":["Gordon","W"],"suffixes":[]},{"propositions":[],"lastnames":["Lemey"],"firstnames":["Philippe"],"suffixes":[]},{"propositions":[],"lastnames":["MacLean"],"firstnames":["Oscar"],"suffixes":[]},{"propositions":[],"lastnames":["Robertson"],"firstnames":["David","L"],"suffixes":[]},{"propositions":["de"],"lastnames":["Oliveira"],"firstnames":["Tulio"],"suffixes":[]},{"propositions":[],"lastnames":["Pond"],"firstnames":["Sergei","L","Kosakovsky"],"suffixes":[]}],"doi":"10.1101/2021.02.23.21252268","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Martin et al. - 2021 - The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the S.pdf:pdf","journal":"medRxiv","keywords":"OA,genomics_fund_ack,original","mendeley-tags":"OA,genomics_fund_ack,original","month":"jul","pages":"2021.02.23.21252268","pmid":"33688681","publisher":"Cold Spring Harbor Laboratory Press","title":"The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape","url":"https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3 https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3.abstract","year":"2021","bibtex":"@article{Martin2021,\r\nabstract = {The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition. {\\#}{\\#}{\\#} Competing Interest Statement JOW has received funding from Gilead Sciences, LLC (completed) and the CDC (ongoing) via grants and contracts to his institution unrelated to this research. {\\#}{\\#}{\\#} Funding Statement DPM is funded by the Wellcome Trust (222574/Z/21/Z) SLKP was supported by the following grants from the U.S. National Institutes of Health R01 AI134384 (NIH/NIAID), R01 AI140970 (NIH/NIAID), and a RAPID award from the US National Science Foundation 2027196 (NSF/DBI,BIO). DLR is funded by the Medical Research Council (MC$\\backslash${\\_}UU$\\backslash${\\_}1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research {\\&} Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. PL acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the EU grant 874850 MOOD and the Wellcome Trust through project 206298/Z/17/Z. JOW was supported by an NIH-NIAID R01 AI135992. SEJ and HT are supported by H3ABioNet, an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) funded by the National Human Genome Research Institute of the National Institutes of Health under Award Number U24HG006941. The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. GWH is supported by a grant from the US National Institutes of Health (1U01Al152151-01) {\\#}{\\#}{\\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No human or animal specimens were used and no ethical clearance was required by the University of Cape Town where the PI of this study was based. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All Data used was obtained from GISAID (which is credited in the manuscript)},\r\nauthor = {Martin, Darren P and Weaver, Steven and Tegally, Houryiah and San, Emmanuel James and Shank, Stephen D and Wilkinson, Eduan and Giandhari, Jennifer and Naidoo, Sureshnee and Pillay, Yeshnee and Singh, Lavanya and Lessells, Richard J and Gupta, Ravindra K and Wertheim, Joel O and Nekturenko, Anton and Murrell, Ben and Harkins, Gordon W and Lemey, Philippe and MacLean, Oscar and Robertson, David L and de Oliveira, Tulio and Pond, Sergei L Kosakovsky},\r\ndoi = {10.1101/2021.02.23.21252268},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Martin et al. - 2021 - The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the S.pdf:pdf},\r\njournal = {medRxiv},\r\nkeywords = {OA,genomics{\\_}fund{\\_}ack,original},\r\nmendeley-tags = {OA,genomics{\\_}fund{\\_}ack,original},\r\nmonth = {jul},\r\npages = {2021.02.23.21252268},\r\npmid = {33688681},\r\npublisher = {Cold Spring Harbor Laboratory Press},\r\ntitle = {{The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape}},\r\nurl = {https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3 https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3.abstract},\r\nyear = {2021}\r\n}\r\n","author_short":["Martin, D. P","Weaver, S.","Tegally, H.","San, E. J.","Shank, S. D","Wilkinson, E.","Giandhari, J.","Naidoo, S.","Pillay, Y.","Singh, L.","Lessells, R. J","Gupta, R. K","Wertheim, J. O","Nekturenko, A.","Murrell, B.","Harkins, G. W","Lemey, P.","MacLean, O.","Robertson, D. L","de Oliveira, T.","Pond, S. L K."],"key":"Martin2021","id":"Martin2021","bibbaseid":"martin-weaver-tegally-san-shank-wilkinson-giandhari-naidoo-etal-theemergenceandongoingconvergentevolutionofthen501ylineagescoincideswithamajorglobalshiftinthesarscov2selectivelandscape-2021","role":"author","urls":{"Paper":"https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3 https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v3.abstract"},"keyword":["OA","genomics_fund_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-YbiDDZeTcX0VKKZlqqSKulhgmeoOpLm","dataSources":["y6ojaHcuarkmc4yRQ"],"keywords":["oa","genomics_fund_ack","original"],"search_terms":["emergence","ongoing","convergent","evolution","n501y","lineages","coincides","major","global","shift","sars","cov","selective","landscape","martin","weaver","tegally","san","shank","wilkinson","giandhari","naidoo","pillay","singh","lessells","gupta","wertheim","nekturenko","murrell","harkins","lemey","maclean","robertson","de oliveira","pond"],"title":"The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape","year":2021}