Multiscale evolution of the 3D genome

The spatial organization of the genome underpins how and when its encoded information is utilized. Nevertheless, a unified understanding of how genome architecture evolves across different life scales is still emerging. This review synthesizes current research on 3D genome evolution from both micro- and macro-perspectives. At cellular-level timescales exemplified by cancer, architectures can evolve rapidly due to frequent genomic mutations and plastic epigenetic marks. Between closely related species, architectural divergence is driven primarily by local genomic alterations, mainly cis-regulatory elements. Across larger phylogenetic distances, genome architectures display striking diversity, yet recurrent higher-order features have nevertheless emerged through convergent evolution, reflecting common functional requirements. The micro-to-macro comparative framework proposed here delineates how the diversity of genome architectures relates to the evolution of form and function.