Abstract: Antimicrobial resistance in Gram-negative organisms is an emerging threat to public health. Since the identification of the first mobile colistin resistance (mcr) gene, mcr-1, in 2015 has attracted worldwide attention. Presently, a total of 10 different mcr-family genes (i.e. mcr-1 to mcr-10) have been described. Here, based on the National Database of Antibiotic-Resistant Organisms and NCBI, we have developed a motif-based mechanism for detecting and differentiating mcr genes. Clustering was done considering the percent identity of 88 such that mcr-1 to mcr-10 are present in 10 clusters. There are additional 39 clusters so we developed motifs for these additional novel mcr classes. This work also showed that mcr genes may circulate silently in the environment a while before being discovered/reported. Further, we investigated the occurrence and global dissemination of known mcr gene variants in publicly available KAUST Metagenomic Analysis Platform (KMAP). In metagenomic data wastewater and humans are significant factors leading to the spread of mcr Antibiotic-Resistant Genes (ARGs) across natural environments. We also applied our motifs on recently available data in a metagenomic study (preprint) to test motif power in distinguishing known classes and possibly new ones.