Hi-C guided assemblies reveal conserved regulatory topologies on X and autosomes despite extensive genome shuffling

Abstract

Genome rearrangements that occur during evolution impose major challenges on regulatory mechanisms that rely on three-dimensional genome architecture. Here, we developed a scaffolding algorithm and generated chromosome-length assemblies from Hi-C data for studying genome topology in three distantly related Drosophila species. We observe extensive genome shuffling between these species with one synteny breakpoint after approximately every six genes. A/B compartments, a set of large gene-dense topologically associating domains (TADs), and spatial contacts between high-affinity sites (HAS) located on the X chromosome are maintained over 40 million years, indicating architectural conservation at various hierarchies. Evolutionary conserved genes cluster in the vicinity of HAS, while HAS locations appear evolutionarily flexible, thus uncoupling functional requirement of dosage compensation from individual positions on the linear X chromosome. Therefore, 3D architecture is preserved even in scenarios of thousands of rearrangements highlighting its relevance for essential processes such as dosage compensation of the X chromosome.

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

“…We found that most orthologous blocks are placed in the same Muller elements, suggesting that even on a small scale, translocations rarely occur between chromosomes during Drosophila evolution ( Fig. 2A), consistent with a recent study (Renschler et al 2019) .…”

“…About 33% (280/859) the synteny breaks are found to be overlapped with TAD boundaries corresponding to 2.5 fold enrichment relative to random expectation ( Fisher exact test, P-value < 0.001) , suggesting chromosomal arrangement breakpoints are not randomly distributed across the genome and might be influenced by genome spatial organization. This pattern was also observed in a recent work (Renschler et al 2019) in which the authors compared D. melanogaster to two distantly related species.…”

“…About ~43% of the TADs were found to be shared between humans and chimpanzees(Eres et al 2019) . About 10% of the TADs are shared among all three distantly related Drosophila species-D. melanogaster , D. busckii and D. virilis -even though with the low degree synteny of their genomes(Renschler et al 2019) . Our comparative Hi-C analysis of D. melanogaster and D. pseudoobscura revealed that at least 40% of the TADs, spanning nearly half of syntenic genomic regions, are still shared.…”

3D genome evolution and reorganization in the Drosophila melanogaster species group

“…Consistent with this prediction, a variety of studies in vertebrates have reported strong conservation of 3D genome organization using comparative Hi-C approaches [8,50,26,28] . A recent study in Drosophila reported that 3D genome architecture is conserved over 40 million years of evolution in spite of extensive chromosomal rearrangements [41]. These studies support a model where chromosomal rearrangements that preserve TADs (i.e.…”

“…Previous studies have identified inconsistencies in TAD-calling software packages [53] and have raised the possibility that TAD conservation results may depend on the direction of the liftover comparison [13]. For example, studies report conservation estimates by first calling TADs in the species for which they have less data and then identifying the orthologous domains in 6 the species for which they have more data [40,8,41]. When reversing the analysis the conservation rate can be reduced by up to 25%.…”