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. 2008 Feb;82(4):1819-26.
doi: 10.1128/JVI.01926-07. Epub 2007 Dec 5.

Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus

Chung-Chau Hon  1 , Tsan-Yuk Lam, Zheng-Li Shi, Alexei J Drummond, Chi-Wai Yip, Fanya Zeng, Pui-Yi Lam, Frederick Chi-Ching Leung
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Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus

Chung-Chau Hon et al. J Virol. .
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Abstract

Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant 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 open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for 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, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV.

Figures

FIG. 1.
Detection of recombination and estimation of a breakpoint within the genome of Rp3. A similarity plot (A) and a bootscan analysis (B) detected a single recombination breakpoint at around the ORF1b/S junction. Both analyses were performed with an F84 distance model, a window size of 1,500 bp, and a step size of 300 bp. The Hu-SCoV group includes strains Tor2 (AY274119), GD01 (AY278489), ZJ01 (AY297028), SZ3 (AY304486), GZ0402 (AY613947), and PC4 (AY613950). (C) Organization of essential ORFs of the SCoV genome and location of the estimated breakpoint. The blue and red horizontal arrows represent the essential ORFs from the major and minor parents, respectively. A sequence alignment of the ORF1b/S junction regions of Rp3, Tor2, and Rm1 is shown below. A consensus IGS and the coding regions of ORF1b and S are annotated above the alignment. The black vertical arrow below the alignment indicates the estimated breakpoint located immediately after the start codon of the S coding region.
FIG. 2.
Phylogenetic origins of the major and minor parental regions of Rp3. ML phylogenies were constructed from the concatenated sequences of the essential ORFs of the major (A) and minor (B) parental regions of selected CoVs. For the purposes of display, the phylogenies were midpoint rooted. The taxa were annotated according to their accession numbers and host species—civets (C), humans (H), or bats (B)—and strain names. The numbers on the left of the nodes refer to the BMCMC posterior probabilities. The percentages of support for all other internal nodes within the two lineages were omitted for simplicity. The recombinant strain Rp3, the most recent common ancestor of Hu-SCoVs (MRCA-Hu), and the divergence event between Hu-SCoVs and HB-SLCoVs (DIV-Hu/HB) are indicated. The scale bars are in units of nucleotide substitutions per site.
FIG. 3.
tMRCA-Hu estimated from the S1 data set. (A) tMRCA-Hu estimated from the S1 data set under various Bayesian clock models and the ML SRDT model. (B) Posterior MCMC samples (left y axis) of tMRCA-Hu estimated from the S1 data set under the UCED model and the lognormal distribution (right y axis) fitted using Easyfit. The values of the parameters for the lognormal distribution are as follows: σ = 0.56, μ = −1.00, and γ = 2.04.
FIG. 4.
Specification of an S1-derived lognormal tMRCA-Hu prior in the analysis of the ORF1 data set under the UCED model. (A) Prior and posterior distributions of tMRCA-Hu. (B) Effects of the tMRCA-Hu prior on the posterior distribution of tDIV-Hu/HB.
FIG. 5.
Estimation of the window period between the cross-species event and the onset of the 2003 SARS epidemic. This time-scaled phylogeny was summarized from all MCMC phylogenies of the ORF1 data set analyzed under the UCED model with the S1-derived tMRCA-Hu prior. The heights of the nodes are represented by the median of their estimates. The HPD of tMRCA-Hu and tDIV-Hu/HB are indicated by gray boxes at these nodes. The taxa were labeled in the same style as in Fig. 2, except their sampling dates were annotated.
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