Evidences of the Recombinant Origin of a Bat SARS-like Coronavirus and its Implications on the Direct Ancestor of SARS Coronavirus

School of Biological Sciences, The University of Hong Kong, Hong Kong, China.; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.; Bioinformatics Institute, University of Auckland, Auckland, New Zealand

^* To whom correspondence should be addressed. Email: fcleung{at}hkucc.hku.hk.

	Abstract

Bats have been identified as the natural reservoir of SARS-like and SARS Coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendent of the direct ancestor of SCoV based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between the ORF1 and S coding region, suggesting the replication intermediates may participate in the recombination event as previously speculated in other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular clock models and an informative prior on the theoretical onset of SARS epidemic, interspecies transfer of this SLCoV lineage from bat to the amplifying host (e.g. civets) was estimated to be happened at a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds lights on the possible host bat species of the direct ancestor of SCoV, providing valuable information to the scope and focus of surveillance for origin of SCoV.