gms | German Medical Science

Molecular epidemiology is becoming an effective tool to study the evolution of novel infectious agents causing emerging diseases [Ref. 1] as well as to search their natural origins [Ref. 2]. The foresight in saving specimens from the critical early stages of the outbreak of the severe acute respiratory syndrome (SARS) and the analysis of epidemiology at the molecular level enabled us to reveal the strong adaptive selection pressures initially influencing the SARS-coronavirus (SARS-CoV) genome during the 2002/2003 epidemic until a stable genotype that evolved to predominate during the latter part of the episode. Genotypes characteristic of each of the early, middle, and late phases of the epidemic were discovered, and the earliest genotypes were similar to those for the animal SARS-like coronaviruses (SARS-like CoV). Major deletions were observed in the Orf8 region of the genome, both at the start and the end of the epidemic. The neutral mutation rate of the viral genome was constant but the amino acid substitution rate of the coding sequences slowed during the course of the epidemic. The spike protein showed the strongest initial responses to positive selection pressures, followed by subsequent purifying selection and eventual stabilization [Ref. 3]. The genomic sequences of both the human SARS-CoV and the palm civet SARS-like CoV isolated during the winter of 2003/2004 were further analyzed together with their epidemiological information and clinical features, which not only confirmed the animal origin of this disease episode but also provided new insight for the future in-depth study of the viral molecular evolution along the course of its host-switch.