Genomic Mutation Dynamics And Molecular Evolution Of SARS Coronavirus

In March 2003, a novel coronavirus (CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). To investigate the origin, transmission, and other characteristics of SARS-CoV, we have sequenced ten SARS-CoV isolates from patient samples and viral cultures, and have analyzed these sequences in comparison with other 115 SARS-CoV sequences available in public databases. With the genome sequence of GZ02 as the reference, we discovered 266 common base substitutions as well as 18 major deletions and 2 insertions among the 125 complete genomes. The distribution of these polymorphisms appeared biased over the whole genome and two major genotypes were identified associated with different epidemiological phases and fatality rates. The polymorphisms in the spike (S) protein showed a strongest positive selection for an initial infection, subsequent purifying selections, and eventual stabilization. A phylogenetic tree was constructed based on the polymorphisms collected. The comparison between the primary and cultured isolates from the same patient samples revealed that most of the sequences were either identical or with only a few detected variations. The variations are assumed resulted from culture processes where selective advantageous mutants became dominant at a time.