was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a novel beta-coronavirus with high pathogenicity, which imposes a serious threat to human health 1 . Substantial evidence has showed that MERS-CoVs have existed in central and east Africa for decades 2,3 , and have many natural hosts including two species of bats (Neoromicia capensis and Vespertilio superans), dromedary camel (Camelus dromedarius), and European hedgehog (Erinaceus europaeus) 4-7 . Yet it seemed that human MERS-CoV first isolated in Saudi Arabian in 2012, and then spread among humans worldwide 8 . Studies of prototype human MERS-CoV also suggested that the tMRCA (the time of most recent common ancestor) of human MERS-CoV can be traced back to about 2011 9 . Because the genome sequence of bat MERS-CoV is highly identical to that of human MERS-CoV, it has been indicated that human MERS-CoV might have a bat origin 10 , while there is also some evidence of camel-to-human MERS-CoV transmission 11,12 . Together, these studies proposed that zoonotic event may play a nontrivial part in MERS-CoV evolution and transmission. Previous studies showed that recombination was common among the members of beta-coronavirus 13,14 . By joining the previously unlinked DNA, recombination event can create new viral strains which may be capable of infecting new hosts and evading host's immuno-responses. The phylogenetic analysis showed that there were two main MERS-CoV clades-clade A and B, and clade B can be further divided into five phylogenetic groups 15 . There is evidence that recombination event had happened between group III and group V 15 . However, whether there was potential recombination event happened between the other groups or among multiple phylogenetic groups remains unclear. The genome of MERS-CoV is over 30,000 nucleotides (nt) in length, which contains seven predicted open reading frames (ORFs) and four structural genes-spike (S), envelope (E), membrane (M), and nucleocapsid (N) 16 (supplementary Fig. 1c ). The surface located spike (S) protein of beta-coronaviruses is one of the major determinants in their cross-species transmission because it mediates the virus-receptor recognition and thereby activates viral infection process 17 . Additionally, the receptor binding domain (RBD) on S protein's N-terminal is the key element for beta-coronavirus entering into host cells and the mutations in coronavirus's RBD affects its infection and cross-species capability 18, 19 . For example, the study of the spike protein from severe acute respiratory syndrome coronavirus (SARS-CoV), another beta-coronavirus with high pathogenicity, revealed four amino
Output: Evolutionary Dynamics of MERS- CoV: Potential Recombination, Positive Selection and Transmission OPEN