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

The relatively fast evolutionary rate means that it is most appropriate to estimate shallow nodes in the sarbecovirus evolutionary history including the divergence times of SARS-CoV and SARS-CoV-2 from their most closely related bat viruses. Accurately estimating deeper nodes would require adequately accommodating time-dependent rate variation. While such models have recently been made available, we lack the information to calibrate the rate decline through time (e.g. through internal node calibrations (Membrebe et al., 2019) ). As a proxy, it would be possible to model the long-term purifying selection dynamics as a major source of time-dependent rates rates (Duchene et al., 2014; Aiewsakun and Katzourakis, 2016; Membrebe et al., 2019) , but this is beyond the scope of the current study. The assumption of long-term purifying selection would imply that coronaviruses are at endemic equilibrium with their natural host species, horseshoe bats, to which they are presumably well-adapted. Although there is currently little evidence supporting or contradicting strong positive selection in the sarbecovirus lineage, if multiple host species were to be identified that are able to support endemic viral transmission, then the positive selection that would be associated with new species adaptations would need to be considered when inferring evolutionary rate variation through time.