Shen, Y. et al. Genome Res. doi:10.1101/gr.193433.115 (13 November 2015).

The Synthetic Yeast Genome Project (Sc2.0), an ongoing effort to synthesize the genome of Saccharomyces cerevisiae, addresses fundamental questions about genome function. To generate phenotypic diversity, Jeff Boeke and his collaborators at Sc2.0 developed SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution) by systematically introducing loxP sites—which undergo recombination in the presence of Cre—in certain chromosomal regions. Although the method was promising, concerns about specificity and decreased diversity remained. Recently Shen et al. tested 64 strains with loxP sites in one arm of chromosome IX. Recombination produced complex structural variants that covered the entire arm. Each strain was unique, and there was no evidence of rearrangement with other nuclear or mitochondrial sites, indicating that SCRaMbLE can be used to target multiple synthetic chromosomes simultaneously.