Evolutionary conservation and divergence of 3D genome organization in Drosophila
Authors: Nicole Torosin; Weihuan Cao; Christopher Ellison
Affiliation: Rutgers University
Keywords: d. evolution of gene expression; z. other (Topologically Associating Domains)
Topologically associating domains (TADs) are 3D organizational units of chromatin that are believed to regulate gene expression by constraining enhancer/promoter interactions. Several early studies found that TADs are highly conserved in both vertebrates and in Drosophila. However, more recent research suggests that TADs may diverge rapidly and that their reorganization is not associated with widespread divergence in gene expression, in contradiction to their supposed role in constraining enhancer/promoter contacts. In this study, we use a comparative genomics approach to estimate the rate of TAD evolution and determine whether the evolutionary conservation of TAD structures is associated with conservation of gene expression. We generated Hi-C chromosome conformation capture data for eleven Drosophila species from the melanogaster group, diverging between 4-32 million years ago. We used a phylogenetic approach to estimate the rate of TAD evolution and found that TADs evolve roughly 10-20-fold faster than other genomic features in Drosophila, such as gene duplicates and chromosomal rearrangements. Next, we found that highly conserved TADs are enriched for the BLACK and BLUE chromatin states which contain Polycomb-repressed and developmentally-regulated genes. These TADs evolve at a significantly slower rate compared to other TADs and show significantly higher constraint in gene expression levels. On the other hand, TADs that are enriched for the YELLOW chromatin state, which contains broadly-expressed, transcriptionally-active genes, evolve faster compared to all TAD domains and show less gene expression constraint. After controlling for chromatin state, we do not find a significant relationship between TAD conservation and interspecies variation in gene expression levels. These results suggest that, in general, most TADs evolve rapidly and their divergence has little effect on gene expression. However, the higher levels of evolutionary conservation and gene expression constraints in TADs enriched for developmentally-regulated chromatin suggests that these TAD subtypes may be more important for regulating gene expression, likely due to the larger number of long-distance enhancer promoter contacts associated with developmental genes.