The Molecular Mechanisms Underlying Hidden Phenotypic Variation among Metallo-B-Lactamases

摘要

Genetic variation among orthologous genes has been largely formed through neutral genetic drift while maintaining the functional role of these genes. However, because the evolution of gene occurs in the context of each host organism, their sequence changes are also associated with adaptation to a specific environment. Thus, genetic variation can create critical phenotypic variation, particularly when genes are transferred to a new host by horizontal gene transfer. Unveiling "hidden phenotypic variation" is particularly important for genes that confer resistance to antibiotics. However, our understanding of the molecular mechanisms that underlie phenotypic variation remains limited. Here we sought to determine the extent of phenotypic variation in the B1 metallo-p-lactamase (MBL) family and its molecular basis by systematically characterizing eight MBL orthologs, including NDM-1 and VIM-2 and IMP-1.