Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have infected human and animals world wide . Since the first SARS-CoV-2 sequences identified from samples collected in December 2019, the virus has been evolving . Now, in the GISAID database of SARS-CoV-2 genomes as of March 17 , 2021 , 95.7% (758,684 of 792,388) of the SARS-CoV-2 genome has the D614G mutation in the spike protein gene; and 22% (178,186 of 792.388) had N501Y mutation which occurred in the more virulent UK variants, South Africa variant and Brazil variant . Large number of minks were infected with the virus which containing the Y453F mutation in Europe, causing zoonosis concerns . To evaluate the genetic characteristics of the US mink-derived SARS-CoV-2 sequences, we analyzed all animal-derived (977), all Canadian (19,529) and US (173,277) SARS-CoV-2 sequences deposited in GISAID from December 2019 to March 12, 2021, and identified 2 dominant novel variants, the N501T-G142D variant and N501T-G142D-F486L variant, in the US mink-derived SARS-CoV-2 sequences . These variants were not found in minks from Canada or other countries . The Y453F mutation was not identified in the mink-derive sequences in the US and Canada . The N501T mutation occurred two months earlier in the human than in the minks in the US . The results of our study highlighted the importance of on going monitoring the mutations of the SARS-CoV-2 virus in animals.