The recent ancestry of Middle East respiratory syndrome coronavirus in Korea has been shaped by recombination

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. Since 2012, the victims have mainly come from the Middle East countries or sporadically from some other geographical regions seeded by the travelers who visited the Middle East. Such an introduction through travelling led to the emergence of a MERS-CoV outbreak in Korea in May 2015, which caused more than 140 confirmed human cases in less than a month. Using 70 complete genome sequences of MERS-CoV isolates, including the most recent sequences for the Korean and Chinese isolates, we reconstructed the phylogenetic relationships of the complete genome and the individual protein coding regions. The Korean MERS-CoV strain clustered in the previously established Hafr-Al-Batin-1_2013 clade together with two Saudi Arabian and one Chinese strain sampled in 2015. Although these four strains remained monophyletic in the entire protein-coding region, this clade showed different phylogenetic relationships across the genome, indicating a shared unique recombination pattern that is different from previously reported putative recombination strains. Our findings suggest that the recent ancestor of the Korean and its related MERS-CoV strains is characterized by unique mosaic genome pattern that is different from other putative recombinants.

Figure 1. Phylogenetic relationships of MERS-CoV complete genome and ORF1ab sequences.

The complete genome (a) and ORF1ab (b) sequences of 70 MERS-CoV strains were investigated for their phylogenetic relationships. In the complete genome tree, six different evolutionary clades were indicated with different colors (clade A, orange; Riyadh-3, lime green; Jeddah-Riyadh, mint; Hafr-Al-Batin-1, peach; Buraidah-1, lavender; and Al-Hasa, magenta). As the color of circles in the tree nodes, the size of circles in the node represents the posterior probability of their clustering (the bigger size, the higher probability). The tip of the Korean strain (KOR002) was denoted with the red color and asterisk.

Figure 2. Phylogenetic relationships of MERS-CoV S and N sequences.

The S (a) and N (b) sequences of 70 MERS-CoV strains were investigated for their phylogenetic relationships. See the detailed legend in the Fig. 1.

Figure 3. Schematic representation of MERS-CoV coding regions and putative recombinant regions detected in the KOR002 strain.

The protein coding regions of MERS-CoV genome (a) were represented together with the putative recombinant regions of KOR002 strain (b) detected by the RDP method using the complete genome sequences of 70 MERS-CoV strains. Phylogenetic relationships of MERS-CoV complete genomes were reconstructed according to each recombinant region. The trees of recombinant regions I (c), II (d), and III (e) were represented with the same color annotations in the Fig. 1. The tip of the Korean strain (KOR002) was denoted with the red color and asterisk. The tip of a parental strain of KOR002 identified (Table 1) was indicated with an arrow.