Reorganization of 3D genome structure in the Drosophila melanogaster species group

Topologically associating domains, or TADs, are functional units that organize chromosomes into 3D structures of interacting chromatin. TADs play an important role in regulating gene expression by constraining enhancer-promoter contacts; there is evidence that deletion of TAD boundaries leads to aberrant expression of neighboring genes. While the mechanisms of TAD formation have been well-studied, current knowledge on the extent of TAD conservation across species is inconclusive. Due to the integral role TADs play in gene regulation, their structure and organization is expected to be conserved during evolution. However, more recent research suggests that TAD structures diverge relatively rapidly.

We use Hi-C chromosome conformation capture to measure evolutionary conservation of whole TADs and TAD boundary elements between D. melanogaster and D. triauraria, two early-branching species from the melanogaster species group which diverged ∼28 million years ago.

We found that 75% of TAD boundaries are orthologous while only 25% of TAD domains are conserved and these are enriched for Polycomb-repressed chromatin. Our results show that TADs have been reorganized since the common ancestor of D. melanogaster and D. triauraria, yet the sequence elements that specify TAD boundaries remain highly conserved. We propose that evolutionary divergence in 3D genome organization results from shuffling of conserved boundary elements across chromosomes, breaking old TADs and creating new TAD architectures. This result supports the existence of distinct TAD subtypes: some may be evolutionarily flexible while others remain highly conserved due to their importance in restricting gene-regulatory element interactions.