Evolutionary analysis of gene ages across TADs associates chromatin topology with whole genome duplications

Topologically associated domains (TADs) are interaction sub-networks of chromosomal regions in 3D genomes. TAD boundaries frequently coincide with genome breaks while boundary deletion is under negative selection, suggesting that TADs may facilitate genome rearrangements and evolution. We show that genes co-localise by evolutionary age in humans and mice, resulting in TADs having different proportions of younger and older genes. We observe a major transition in the age co-localisation patterns between the genes born during vertebrate whole genome duplications (WGDs) or before, and those born afterwards. We also find that genes recently duplicated in primates and rodents are more frequently essential when they are located in old-enriched TADs and interact with genes that last duplicated during the WGD. Therefore, the evolutionary relevance of recent genes may increase when located in TADs with established regulatory networks. Our data suggests that TADs could play a role in organising ancestral functions and evolutionary novelty. HighlightsO_LITADs coincide with clusters of genes that are close in their evolutionary age. C_LIO_LIWhole genome duplications mark a transition in gene age co-localisation clusters. C_LIO_LIGene age co-localisation patterns are associated with TAD insulation. C_LIO_LIYoung essential genes share TADs and interact with old genes. C_LI