The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Moderate mutation rate in the SARS coronavirus genome and its implications
Open accessAbstract
BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 - 2.38 x 10-3 nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 - 3.30 x 10-3 and 1.67 - 4.67 x 10-3 per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.
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“For the SARS-CoV-2 genome, the nonsynonymous to synonymous substitutions ratio is 0.028, indicating strong purifying selection [32].”
From Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe (2022) · cites this paper as [32]
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Metadata
- Authors
- Zhao, Z., Li, H., Wu, X., Zhong, Y., Zhang, K., Zhang, Y.-P., Boerwinkle, E., & Fu, Y.-X.
- Affiliations
- Virginia Commonwealth University (US)
- The University of Texas Health Science Center at Houston (US)
- Kunming Institute of Zoology (CN)
- Yunnan University (CN)
- Corresponding author
- Fu, Yun-Xin
- Venue
- BMC Evolutionary Biology
- Published
- 2004-06-28
- Volume
- 4
- Issue
- 1
- Pages
- 21-21
- ISSN
- 1471-2148 (ISSN-L)
- PMC
- PMC446188
- OpenAlex
- W2134250657
- Cited by
- 286
- References
- 38
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 30 · 2021: 93 · 2020: 112 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Evolutionary Biology (publishedVersion)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Virginia Commonwealth University
- Yunnan University
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV, mutation rate, viral evolution, single nucleotide polymorphisms, divergence time estimation, most recent common ancestor, emergence timing, RNA viruses, SARS epidemic
- MeSH terms
- Genes, Viral, Phylogeny, Viral Structural Proteins, Mutagenesis, Genome, Viral, Coronavirus, Evolution, Molecular, Severe acute respiratory syndrome-related coronavirus
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