SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission
- Nicolae Sapoval1,
- Medhat Mahmoud2,
- Michael D. Jochum3,
- Yunxi Liu1,
- R.A. Leo Elworth1,
- Qi Wang4,
- Dreycey Albin4,
- Huw A. Ogilvie1,
- Michael D. Lee5,6,
- Sonia Villapol7,
- Kyle M. Hernandez8,9,
- Irina Maljkovic Berry10,
- Jonathan Foox11,
- Afshin Beheshti12,
- Krista Ternus13,
- Kjersti M. Aagaard3,
- David Posada14,15,16,
- Christopher E. Mason11,
- Fritz J. Sedlazeck2,17 and
- Todd J. Treangen1,17
- 1Department of Computer Science, Rice University, Houston, Texas 77005, USA;
- 2Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
- 3Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA;
- 4Systems, Synthetic, and Physical Biology (SSPB) Graduate Program, Rice University, Houston, Texas 77005, USA;
- 5Exobiology Branch, NASA Ames Research Center, Mountain View, California 94043, USA;
- 6Blue Marble Space Institute of Science, Seattle, Washington 98104, USA;
- 7Department of Neurosurgery, Houston Methodist Research Institute, Houston, Texas 77030, USA;
- 8Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;
- 9Center for Translational Data Science, University of Chicago, Chicago, Illinois 60637, USA;
- 10Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA;
- 11Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York 10021, USA;
- 12KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, California 94035, USA;
- 13Signature Science, LLC, Austin, Texas 78759, USA;
- 14CINBIO, Universidade de Vigo, 36310 Vigo, Spain;
- 15Department of Biochemistry, Genetics, and Immunology, Universidade de Vigo, 36310 Vigo, Spain;
- 16Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36213 Vigo, Spain
Abstract
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 SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.
Footnotes
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↵17 These authors share senior authorship.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.268961.120.
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Freely available online through the Genome Research Open Access option.
- Received July 16, 2020.
- Accepted February 12, 2021.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
