Recombination and convergent evolution led to the emergence of 2019 Wuhan coronavirus

The recent outbreak of a new coronavirus (2019-nCoV) in Wuhan, China, underscores the need for understanding the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. Here, we show that recombination in betacoronaviruses, including human-infecting viruses like SARS and MERS, frequently encompasses the Receptor Binding Domain (RBD) in the Spike gene. We find that this common process likely led to a recombination event at least 11 years ago in an ancestor of the 2019-nCoV involving the RBD. Compared with bat isolates, the recent ancestors of 2019-nCoV accumulated a high number of amino acid substitutions in the RBD and likewise in a region of polyprotein Orf1a that is critical for viral replication and transcription. Among these recent mutations, we identify amino acid substitutions common to the SARS 2003 outbreak isolates in positions 427N and 436Y, indicating potential adaptive convergent evolution. Both 427N and 436Y belong to a helix that appears to interact with the human ACE2 receptor. In sum, we propose a two-hit scenario in the emergence of the 2019-nCoV virus whereby the 2019-nCoV ancestors in bats first acquired genetic characteristics of SARS by incorporation of a SARS-like RBD through recombination before 2009, and subsequently, those recombinants underwent convergent evolution.