Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis

Wang, Yanqun; Liu, Di; Shi, Weifeng; Lu, Roujian; Wang, Wenling; Zhao, Yanjie; Deng, Yao; Zhou, Weimin; Ren, Hongguang; Wu, Jun; Wang, Yu; Wu, Guizhen; Gao, George F.; Tan, Wenjie

Our results indicate that at the whole-genome level, ChinaGD01 is Ͼ99% similar to the previously identified MERS-CoV strains. Phylogenetic analysis based on the whole-genome sequence revealed that it belongs to group 3 of clade B MERS-CoV strains and forms a separate small branch with viruses from South Korea and Saudi Arabia from 2015. Different phylogenies were observed in the trees constructed using the full-length genome and the S gene, indicating the possibility of a recombination event. Further evidence of a recombination event was obtained through bootscanning and SNP analyses. BEAST analysis revealed that it might have occurred recently, in the second half of 2014, in the Middle East. Genetic recombination has been well established in severe acute respiratory syndrome coronavirus (SARS-CoV) (17, 18) ; however, there is only one report of genetic recombination in MERS-CoV (19) . Dudas and Rambaut point to frequent recombination in MERS-CoV and partition the genome into two parts in which nucleotides 1 to 23,722 and nucleotides 23,723 to 30,126 have independent molecular clock rates. Based on the latest genome sequences from South Korea and the Kingdom of Saudi Arabia, our research indicated that a novel type of genetic recombination has occurred in the MERS-CoV strains prevalent in South Korea. We note that six MERS-CoV isolates from 2015 (ChinaGD01, the first MERS-CoV strain from South Korea, and the four latest strains from Saudi Arabia) had high levels of nucleotide identity (99.90% to 99.96%) and showed the same recombination signal in our analyses. We speculate that they arose from a common recombination event. However, more studies are needed to understand the relationship between genetic recombination of MERS-CoV, the biological properties it conveys, and its relevance to the recent high rate of transmission.