Moderate mutation rate in the SARS coronavirus genome and its implications

Area of Science:

• Virology
• Molecular Evolution
• Epidemiology

Background:

• The 2003 severe acute respiratory syndrome (SARS) epidemic, caused by SARS-CoV, resulted in significant global mortality and morbidity.
• Genomic sequencing of SARS-CoV has advanced understanding, but its evolutionary rate and emergence time remain poorly defined.
• Anticipation of future SARS-CoV outbreaks necessitates a clear understanding of its evolutionary mechanisms.

Purpose of the Study:

• To estimate the mutation rate of SARS-CoV.
• To determine the emergence time of SARS-CoV in the human population.
• To provide insights into the evolutionary dynamics of SARS-CoV for pandemic preparedness.

Main Methods:

• Analysis of 16 complete SARS-CoV genomic sequences with associated clinical data.
• Identification of single nucleotide variations through multiple-sequence alignment.
• Estimation of mutation rates using three distinct strategies to mitigate sequencing errors and cell culture artifacts.

Main Results:

• An estimated SARS-CoV genome mutation rate of 0.80 - 2.38 x 10^-3 nucleotide substitutions per site per year was determined.
• Non-synonymous and synonymous substitution rates were calculated at 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 for the analyzed sequences was inferred to have emerged in spring 2002.

Conclusions:

• The mutation rates of SARS-CoV are comparable to other coronaviruses and moderate relative to other RNA viruses.
• Inferred mutation rates suggest SARS-CoV may have been present in humans since spring 2002 before causing a major epidemic.
• Understanding SARS-CoV's evolutionary rate is crucial for predicting and managing future epidemics.