Topologically associating domains and their role in the evolution of genome structure and function inDrosophila

Abstract

Topologically associating domains (TADs) are regarded as functional and structural units of higher-order spatial genome organization of many eukaryotic genomes. However, our knowledge of how evolution affects TADs remains limited. To decipher the evolutionary significance of TADs, we de novo assembled the genome of D. pseudoobscura and created a high-resolution (~800 bp) Hi-C contact map to annotate TADs. Remarkably, more than 40% of TADs between D. pseudoobscura and D. melanogaster are conserved, despite extensive chromosomal rearrangement in the ~49 million years since they shared a common ancestor. Comparison of 17 diverse Drosophila species genomes revealed enrichment of genome rearrangement breakpoints at the TAD boundaries but depletion of such breaks inside the TADs themselves. We show that conservation of TADs is associated with gene expression stability across tissues. Surprisingly, despite being larger mutational targets, a substantial proportion of long (>50kb) genes in D. melanogaster (42%) and D. pseudoobscura (26%) are individually spanned by complete TADs, implying the formation and maintenance of TADs via 3D cis-regulatory interactions commonly found within long genes. U sing high-confidence genome-wide structural variant datasets from 14 D. melanogaster strains, its 3 closest sibling species from the D. simulans species complex, and two obscura clade species, we show evidence of natural selection operating on structural variants at the TAD boundaries, but with the nature of selection differing between the SV types. Deletions are significantly depleted at TAD boundaries for both divergent and polymorphic SVs, suggesting that deletions at TAD boundaries are under purifying selection, whereas divergent duplications are enriched at the TAD boundaries, pointing to positive selection. Our results offer novel insights into the evolutionary role and maintenance of TADs and their significance in genome structure evolution and gene regulation.

Evolutionary Genomics of Structural Variation in Asian Rice (Oryza sativa) Domestication

“…2018 ) assemblies. Genome assembly-based SV discovery was also performed using the pipeline previously described ( Liao et al. 2020 ).…”

The Easter Egg Weevil (Pachyrhynchus) genome reveals synteny in Coleoptera across 200 million years of evolution

“…Recent studies in Diptera have demonstrated that syntenic breakpoints tend to occur at the boundaries between TADs (Renschler et al 2019, Liao et al 2020, Lukyanchikova et al 2020. Despite having many breakpoints, with relatively few chromosome translocations, the dipteran chromosomes largely remain intact (Bracewell et al 2019).…”

“…These results of gene order conservation are consistent with research of Drosophila topological associated domains (TADs) that showed synteny break points at approximately every 6th gene between D. melanogaster, D. virilis and D. busckii , which have a similar level of divergence as the Drosophila taxa we examined, about 40 Ma of divergence (Renschler et al 2019). In addition, the chromosomal rearrangement across Drosophila tends to occur at TAD boundaries, not inside the loops (Renschler et al 2019, Liao et al 2020). In Anopheles mosquitos, the TAD structures seem to be associated with cytological structures as well (Lukyanchikova et al 2020).…”

Chromatin Structure and Function in Mosquitoes

“…Despite some controversy on whether genome conformation or transcription is more important to gene control ( Ing-Simmons et al, 2020 ), it is well-established that TAD structure plays a role in transcriptional regulation ( Beagan and Phillips-Cremins, 2020 ). Several studies in Drosophila and other eukaryotes have shown that disruption of TAD boundaries and TAD rearrangements alter enhancer-promoter interactions and dysregulate gene expression ( Liao et al, 2020 ). This has led to suggestions that TAD structure should be highly evolutionary constrained between related species, for example, across dipterans.…”

“…This has led to suggestions that TAD structure should be highly evolutionary constrained between related species, for example, across dipterans. Indeed, TADs have been shown to be conserved across Drosophila species ( Renschler et al, 2019 ; Liao et al, 2020 ; Torosin et al, 2020 ). However, the differences in TAD length reported above between Anopheles spp., Ae.…”