evidence: Therefore, the S protein of SARS-CoV-2 continues to diversify due to its propensity for mutation and recombination. In addition, widespread infection among humans is now posing additional threats to other mammals that interact with human populations, as secondary and even tertiary transmissions between humans and other mammals can occur65. Such cross-specific transmission can further enable the emergence of potentially dangerous recombinant SARS-CoV-2 strains. It is imperative that epidemiological, genetic, and functional studies of variants be fully utilized to determine how to slow down and ultimately eradicate within- and between-species transmissions. [...] Fiorentini, S. et al. First detection of SARS-CoV-2 spike protein N501 mutation in Italy in August, 2020. Lancet Infect. Dis.https://doi.org/10.1016/S1473-3099(21)00007-4. [...] A confluence of historic gene swapping and evolutionary optimizations and adaptations helped make the coronavirus causing COVID-19 so infectious to people. Devika Singh and Soojin Yi from the Georgia Institute of Technology in Atlanta, USA, discuss the molecular evidence for ancestral recombination events and natural selection in the genome of SARS-CoV-2, the coronavirus responsible for COVID-19. In particular, the spike protein that enables viral entry into human cells shows ample signs of these evolutionary processes, which probably facilitated the virus’s spillover from other animals into humans. New variants of SARS-CoV-2 that have rapidly spread during the pandemic point to ongoing evolutionary processes, including effects of both potential functional alteration and random genetic drift. A better understanding of the virus’s evolutionary trajectory could help inform efforts to contain SARS-CoV-2 and prevent future pandemics.