TAD conservation in vertebrate genomes is driven by stabilising selection.

Background Topologically Associating Domains (TADs) are fundamental structural and gene regulatory components of chromatin defined by regions of high intra-domain contact frequency. Though TADs are found across diverse metazoans, the extent of their evolutionary conservation is still debated. Some studies indicate significant conservation among closely related species, while others suggest considerable variability, raising questions about the evolutionary forces that preserve TAD organization. Results Here, we investigated the evolutionary conservation of TADs by analysing Hi-C data from 12 vertebrate species. We examined TAD numbers, borders, and gene positioning within TADs. We found that TAD’s features are all highly conserved across species, but this conservation tends to decrease with evolutionary distance. Closely related species show greater TAD conservation compared to more distantly related species. Yet, modelling the divergence in TAD conservation using Ornstein-Uhlenbeck (OU) process revealed considerable selective pressures on TAD number within syntenic blocks, suggesting that TAD features in these genomic regions are under stabilising selection. However, we also identified a small subset of blocks where TAD numbers evolve under genetic drift, highlighting the existence of distinct groups of blocks subject to different evolutionary dynamics. Conclusions These findings improve our understanding of TAD conservation and evolution, revealing significant conservation of TAD features, especially among closely related species. We discovered that TADs evolve both under stabilizing selection and genetic drift, highlighting the complex evolutionary dynamics of TAD evolution.