Beyond nature's clock: Accelerating genomic diversity through hypermutation

Gene mutation is the primary source of genetic variation, yet natural mutation rates are insufficient to meet the demands of biotechnological applications. This review systematically examines advancements in hypermutation technologies designed to overcome this limitation, focusing on targeted, multi-target, and genome-wide approaches, and their transformative applications across diverse fields. By comparing these tools across multiple dimensions, including mutation scope, rate, and type, we provide insights to guide the selection of optimal mutagenesis tools for accessing distinct genetic landscapes and addressing practical challenges. Furthermore, we summarize the challenges that persist in this active area and highlight future directions such as developing high-throughput screening methods and AI-driven predictive models for mutational outcomes. By bridging the gap between natural mutation constraints and biotechnological needs, hypermutation technologies promise to unlock unprecedented innovations in synthetic biology, evolutionary research, and industrial applications and pave the way for exploring previously inaccessible genetic landscapes.