Synthetic genome rearrangement reveals dynamics of chromosome evolution shaped by hierarchical chromatin organization

Synthetic genome evolution provides a dynamic approach to systematically and straightforwardly explore evolutionary processes. SCRaMbLE is an evolutionary system intrinsic to the synthetic yeast genome that can rapidly drive structural variations. Here, we detect over 260,000 rearrangement events after SCRaMbLEing of a novel yeast strain harboring 6 synthetic yeast chromosomes. Remarkably, we find that the rearrangement events exhibit a specific landscape of rearrangement frequency. We further reveal that the landscape is shaped by combinatorial effects of chromatin accessibility and spatial contact probability. The rearrangements tend to occur in 3D spatially proximal and chromatin-accessible regions. Enormous numbers of rearrangements by SCRaMbLE provide a driving force to potentiate directed genome evolution, and investigation of the rearrangement landscape offers mechanistic insights into the dynamics of genome evolution.