دورية أكاديمية
Patterns of within-host genetic diversity in SARS-CoV-2
العنوان: | Patterns of within-host genetic diversity in SARS-CoV-2 |
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المؤلفون: | Tonkin-Hill, Gerry, Martincorena, Inigo, Amato, Roberto, Lawson, Andrew, Gerstung, Moritz, Johnston, Ian, Jackson, David, Park, Naomi, Lensing, Stefanie, Quail, Michael, Gonçalves, Sónia, Ariani, Cristina, Chapman, Michael Spencer, Hamilton, William, Meredith, Luke, Hall, Grant, Jahun, Aminu, Chaudhry, Yasmin, Hosmillo, Myra, Pinckert, Malte, Georgana, Iliana, Yakovleva, Anna, Caller, Laura, Caddy, Sarah, Feltwell, Theresa, Khokhar, Fahad, Houldcroft, Charlotte, Curran, Martin, Parmar, Surendra, Alderton, Alex, Nelson, Rachel, Harrison, Ewan, Sillitoe, John, Bentley, Stephen, Barrett, Jeffrey, Torok, Estee, Goodfellow, Ian, Langford, Cordelia, Kwiatkowski, Dominic, The COVID-19 Genomics UK (COG-UK) Consortium, Wellcome Sanger Institute COVID-19 Surveillance Team |
بيانات النشر: | Cold Spring Harbor Laboratory Wellcome Trust Sanger Institute Department of Pathology Department of Medicine Department of Genetics //dx.doi.org/10.1101/2020.12.23.424229 |
سنة النشر: | 2022 |
المجموعة: | Apollo - University of Cambridge Repository |
مصطلحات موضوعية: | The COVID-19 Genomics UK (COG-UK) Consortium, Wellcome Sanger Institute COVID-19 Surveillance Team |
الوصف: | Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1,181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within and between host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
العلاقة: | https://www.repository.cam.ac.uk/handle/1810/343655Test |
DOI: | 10.17863/CAM.91081 |
الإتاحة: | https://doi.org/10.17863/CAM.91081Test https://www.repository.cam.ac.uk/handle/1810/343655Test |
حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
رقم الانضمام: | edsbas.359CCC3F |
قاعدة البيانات: | BASE |
DOI: | 10.17863/CAM.91081 |
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