Endless forms – how genome organization underlies evolution and development

Within the nucleus of each human cell, ∼2 m of linear DNA is compacted and organized. The structures and principles of genome organization are developmentally regulated and broadly evolutionarily conserved. However, conclusive links between genome structure and function have been difficult to find. In this Review, we provide an overview of mammalian genome organization, highlight recent studies demonstrating how it interacts with evolutionary diversity, and explore its contributions to development. We propose an innovative perspective – that variability in genome organization supports plastic cell fates in multicellular organisms – and draw analogies to show how evolutionary variation can inform study of the function of genome organization.