The authors have constructed a synthetic chromosome arm of the yeast Saccharomyces cerevisiae, laying the groundwork for creating a synthetic eukaryotic genome. A ∼90 kb stretch of the right arm of chromosome IX was designed in silico to remove unstable elements such as transposons and to facilitate genome manipulations. The synthetic sequence, which was swapped into the endogenous genomic region, also contains an inducible evolution system, SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution), which triggers combinatorial rearrangements to allow the study of complex phenotypes.