4.7 Article

SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission

Journal

GENOME RESEARCH
Volume 31, Issue 4, Pages 635-644

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.268961.120

Keywords

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Funding

  1. Department of Computer Science, Rice University
  2. Rice University
  3. C3.ai Digital Transformation Institute COVID-19 award (C3.ai DTI)
  4. National Institutes of Health (NIH) from the National Institute of Child Health and Human Development [R01HD091731]
  5. Baylor College of Medicine under the Division of Intramural Research, National Institute of Allergy and Infectious Diseases [U19AI144297-01]
  6. Translational Research Institute for Space Health through National Aeronautics and Space Administration [NNX16AO69A (T-0404)]
  7. KBR, Inc.
  8. European Research Council [ERC-617457-PHYLOCANCER]
  9. Spanish Ministry of Economy and Competitiveness [PID2019-106247GB-I00]
  10. Fondo Supera COVID19 (EPICOVIGAL)
  11. Xunta de Galicia [CT850A-2]

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The study found that despite the rapid mutation rate of SARS-CoV-2, there is relatively less single nucleotide polymorphism (SNP) diversity between different lineages. The research also showed that intra-host single nucleotide variant (iSNV) and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Additionally, insertions and deletions contribute significantly to the genetic diversity of SARS-CoV-2.
The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 lineages that have spread throughout the world. In this study, we investigated 129 RNA-seq data sets and 6928 consensus genomes to contrast the intra-host and inter-host diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights intra-host single nucleotide variant (iSNV) and SNP similarity, albeit with differences in C > U changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of insertions and deletions contribute to the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARSCoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.

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