Vertebrate whole genome duplications shaped the current 3D genome architecture
Topologically associated domains (TADs) are interaction sub-networks of 3D genomes. TAD boundaries frequently coincide with genome breaks while their deletion is under negative selection, suggesting that TADs act as modules facilitating genome rearrangements and metazoan evolution. However, the role of TADs in the evolution of gene regulation and essentiality is not well understood. Here, we show that TADs play a role organising ancestral functions and evolutionary novelty. We discovered that genes co-localise by evolutionary age in the human and mouse genomes, resulting in TADs that have different proportions of younger and older genes. A major transition in the TAD age co-localisation patterns is observed between the genes born as a result of the vertebrate whole genome duplications (WGDs) or before, and those born afterwards. We also found that primate- and rodent-specific genes are more frequently essential when they are located in 'aged' TADs and connected to genes that have not duplicated since the WGD. Our data suggests that evolutionary success of recent genes may increase when located in functionally relevant TADs with established regulatory networks.