Characterization of SARS Coronavirus Genomes in Taiwan: Molecular Epidemiololgy and Genome Evolution. Shiou-Hwei Yeh1,2, Hurng-Yi Wang3, Ching-Yi Tsai2, Chuan-Liang Kao4, Jyh-Yuan Yang5, Hwan-Wun Liu6, Ih-Jen Su5, Shih-Feng Tsai1, Ding-Shinn Chen2,7,8, Pei-Jer Chen2,7,8 and the National Taiwan University SARS Research Team. 1. 2. 3. 4. 5. 6. 7. 8. Division of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. Institute of Molecular Biology, Academia Sinica, Taiwan. Department of Medical Technology, National Taiwan University, Taipei, Taiwan. Center for Disease Control, Taipei, Taiwan. Institute of Preventive Medicine, National Defense Medical College, Taiwan. Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taiwan. Abstract: Since early March 2003, severe acute respiratory syndrome (SARS) coronavirus infection claimed 346 cases and 37 mortalities in Taiwan. The endemic occurred in two stages. The first stage began in early March to mid-April when all cases had clear contact histories (mostly from Guangdong or Hong Kong) and caused limited familial or hospital infections. The second stage followed, with a large outbreak in a municipal hospital and quickly spread out to northern and southern Taiwan from late April to mid-June. In this stage, there were even some sporadic cases in whom contact could not be traced. Identifying the origin of the SARS virus has become so critical that the infection sources and transmission routes can be traced, leading to subsequent implementation of effective control measures. To address this, we therefore conducted a viral lineage study by sequencing the entire genome of SARS-CoV from ten patients. SARS viruses isolated from Taiwan were found closely related to those from Guangdong and Hong Kong. In addition, all cases from the second stage endemic belonged to the same lineage following the municipal hospital outbreak, including the patients without an apparent contact history. Analyses of these full-length sequences showed a positive selection occurring during SARS-CoV virus evolution. The mismatch distribution indicated that SARS viral genomes did not reach equilibrium and suggested a recent introduction of the viruses into human populations. The estimated genome mutation rate demonstrated SARS-CoV possibly one of the lowest rates among known RNA viruses.