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The genomic features described here may in part explain the infectiousness and transmissibility of SARS-CoV-2 in humans. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observe all notable SARS-CoV-2 features - including the optimized RBD and polybasic cleavage site - in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible. More scientific data could swing the balance of evidence to favor one hypothesis over another. Obtaining related virus sequences from animal sources would be the most definitive way of revealing virus origins. For example, a future observation of an intermediate or fully formed polybasic cleavage site in an SARS-CoV-2-like virus from animals would lend even further support to the natural selection hypotheses. It would also be helpful to obtain more genetic and functional data about SARS-CoV-2, including animal studies. The identification of a potential intermediate host of SARS-CoV-2, as well as the sequencing of very early cases would similarly be highly informative. Irrespective of the exact mechanisms of how SARS-CoV-2 originated via natural selection, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance. Acknowledgements We thank all those who have contributed sequences to the GISAID database (​https://www.gisaid.org/​) and analyses to Virological.org (​http://virological.org/​). We thank M. Farzan for discussions. We thank the Wellcome Trust for support. KGA is a Pew Biomedical Scholar and is supported by NIH grant U19AI135995. AR is supported by the Wellcome Trust (Collaborators Award 206298/Z/17/Z - ARTIC network) and the European Research Council (grant agreement no. 725422 - ReservoirDOCS). ECH is supported by an ARC Australian Laureate Fellowship (FL170100022). RFG is supported by NIH grants U19AI135995, U54 HG007480 and U19AI142790. Competing Interests RFG is co-founder of Zalgen Labs, a biotechnology company developing countermeasures to emerging viruses. None of the other authors declare any conflicts of interest.