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A mutation analysis of SARS-CoV-2 genomes collected around the world sorted by sequence, date, geographic location, and species has revealed a large number of variants from the initial reference sequence in Wuhan. This analysis also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations in the spike protein receptor binding domain (RBD), often occurring in specific combinations, has transferred back into humans. The viral genomic mutations in minks observed in the Netherlands and Denmark show the potential for new mutations on the SARS-CoV-2 spike protein RBD to be introduced into humans by zoonotic transfer. Our data suggests that close attention to viral transfer from humans to farm animals and pets will be required to prevent build-up of a viral reservoir for potential future zoonotic transfer. • SARS-CoV-2 spike protein mutations have shown a pattern of zoonotic transfer. • Pairing of certain spike mutations allows for viral infectivity between species. • Mutations via zoonosis in Europe have also appeared independently in the US. • Mutations assisted through zoonotic transfer could affect pharmaceutical intervention. • Sequencing efforts for a pandemic-causing virus should include a wide range of host species. [ABSTRACT FROM AUTHOR]