Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic

Maciej F Boni; Philippe Lemey; Xiaowei Jiang; Tommy Tsan-Yuk Lam; Blair Perry; Todd Castoe; Andrew Rambaut; David L Robertson

In the absence of a strong temporal signal, we sought to identify a suitable prior rate distribution to calibrate the time-measured trees by examining several coronaviruses sampled through time, including HCoV-OC43, MERS-CoV, and SARS-CoV virus genomes. These data sets were subjected to the same recombination masking approach as NRA3 and were characterized by a strong temporal signal (Figure 4 ), but also by markedly different evolutionary rates. Specifically, using a formal Bayesian approach (Suchard et al., 2018) (see Methods), we estimate a fast evolutionary rate (0.00169 subst/site/yr, 95% highest posterior density We infer time-measured evolutionary histories using a Bayesian phylogenetic approach while incorporating rate priors based on the mean MERS-CoV and HCoV-OC43 rates and with standard deviations that allow for more uncertainty than the empirical estimates for both viruses (see Methods). Using both prior distributions, this results in six highly similar posterior rate estimates for NRR1, NRR2, and NRA3, centered around 0.00055 subst/site/yr. The fact that these estimates lie in between the MERS-CoV and HCoV-OC43 . CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015008 doi: bioRxiv preprint 14 / 25 rate is consistent with the intermediate sampling time range of about 18 years ( Figure 5 ). The consistency of the posterior rates for the different prior means also implies that the data do contribute to the evolutionary rate estimate despite the fact that a temporal signal was visually not apparent ( Figure S1 ). Below, we report divergence time estimates based on the HCoV-OC43-centred rate priors, but also summarize similar corresponding estimates for the MERS-CoV-centred rate priors in Supplementary Figure S3 . The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015008 doi: bioRxiv preprint 15 / 25 are in general agreement with estimates using NRR2 and NRA3, which result in divergence times of 1982 [1948,2009] and 1948 [1879-1999] , respectively, for SARS-CoV-2, and estimates of 1952 [1906, 1989] and 1970 [1932-1996] , respectively, for the divergence time of SARS-CoV from its closest known bat ancestor.