简介：AbstractThe recently emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread around the world. Although many consensus mutations of the Omicron variant have been recognized, little is known about its genetic variation during its transmission in the population. Here, we comprehensively analyzed the genetic differentiation and diversity of the Omicron variant during its early outbreak. We found that Omicron achieved more structural variations, especially deletions, on the SARS-CoV-2 genome than the other four variants of concern (Alpha, Beta, Gamma, and Delta) in the same timescale. In addition, the Omicron variant acquired, except for 50 consensus mutations, seven great new non-synonymous nucleotide substitutions during its spread. Three of them are on the S protein, including S_A701V, S_L1081V, and S_R346K, which belong to the receptor-binding domain (RBD). The Omicron BA.1 branch could be divided into five divergent groups spreading across different countries and regions based on these seven novel mutations. Furthermore, we found that the Omicron variant possesses more mutations related to a faster transmission rate than the other SARS-CoV-2 variants by assessing the relationship between the genetic diversity and transmission rate. The findings indicated that more attention should be paid to the significant genetic differentiation and diversity of the Omicron variant for better disease prevention and control.