SCRaMbLE: a versatile tool for genome manipulation

Genomic rearrangements play an important role in shaping genetic diversity, as they enable the generation of novel structural variations through specific genome manipulation tools. These variations contribute to phenotypic differences among individuals within a population, thereby serving as the foundation for natural selection and driving evolutionary processes. In recent years, Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) has emerged as a promising tool for studying genomic rearrangements. SCRaMbLE utilizes site-specific recombination mediated by loxPsym sites to induce targeted chromosomal rearrangements in yeast cells. In this review, we provide a comprehensive overview of recent advancements in optimization strategies of the SCRaMbLE system and discuss influential factors that affect its performance based on recent research findings. We demonstrate how the SCRaMbLE system can be employed for pathway engineering, phenotype improvement, genome minimization, and dissection of genotype-to-phenotype relationships. We highlight both the advantages and challenges associated with SCRaMbLE and envision its potential applications beyond yeast genetics.