Dynamics of synthetic yeast chromosome evolution shaped by hierarchical chromatin organization

Abstract Synthetic genome evolution provides a dynamic approach to systematically and straightforwardly explore the evolutionary processes. SCRaMbLE is an evolutionary system intrinsic to the synthetic yeast genome that can rapidly drive structural variations. Here, we detected over 260,000 rearrangement events after SCRaMbLEing of a synthetic strain harboring 6 synthetic yeast chromosomes. Remarkably, we found that the rearrangement events exhibited a specific landscape of rearrangement frequency. We further revealed that the landscape was 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 population genomic resource offers mechanistic insights into the dynamic genome evolution.