Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission
- Nicolae Sapoval1,
- Medhat Mahmoud2,
- Michael Jochum3,
- Yunxi Liu1,
- R.A. Leo Elworth1,
- Qi Wang4,
- Dreycey Albin4,
- Huw Ogilvie1,
- Michael D. Lee5,
- Sonia Villapol6,
- Kyle Hernandez7,
- Irina Maljkovic Berry8,
- Jonathan Foox9,
- Afshin Beheshti10,
- Krista Ternus11,
- Kjersti Aagaard2,
- David Posada12,
- Christopher Mason13,
- Fritz J Sedlazeck2 and
- Todd J Treangen1,14
- 1 Rice University;
- 2 Baylor College of Medicine;
- 3 Baylor College of Medicine and Texas Children's Hospital;
- 4 Systems, Synthetic, and Physical Biology (SSPB) Graduate Program;
- 5 NASA Ames Research Center, Blue Marble Space Institute of Science;
- 6 Houston Methodist Research Institute;
- 7 University of Chicago;
- 8 Walter Reed Army Institute of Research;
- 9 Weill Cornell Medicine;
- 10 NASA Ames Research Center;
- 11 Signature Science, LLC;
- 12 CINBIO, Universidade de Vigo, Galicia Sur Health Research Institute;
- 13 Weill Cornell Medical College
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 datasets and 6,928 consensus genomes to contrast the intrahost and interhost diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights 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.
- Received July 16, 2020.
- Accepted February 12, 2021.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International license), as described at http://creativecommons.org/licenses/by-nc/4.0/.
