Spatial genome organization in nematodes with programmed DNA elimination.

Abstract

Programmed DNA elimination (PDE) is a notable exception to genome integrity. In many nematodes, PDE is initiated by DNA double-strand breaks (DSBs), leading to chromosome fragmentation and subsequent DNA loss. However, the mechanism of nematode programmed DNA breakage remains largely unclear. In the human and pig parasitic nematode Ascaris (Ascaris lumbricoides and Ascaris suum), no conserved motif or sequence structures are present at chromosomal breakage regions (CBRs), suggesting the recognition of CBRs may be sequence independent. Using Hi-C, we reveal that Ascaris CBRs engage in three-dimensional (3D) interactions before and during PDE, indicating that physical contacts between break regions may contribute to PDE. The 3D interactions are established in both Ascaris male and female germlines, demonstrating inherent genome organization associated with the CBRs and to-be-eliminated sequences. In contrast, in the unichromosomal horse parasite Parascaris univalens, transient pairwise interactions between neighboring CBRs that will form the ends of future somatic chromosomes are observed only during PDE. We find that Ascaris PDE, which converts 24 germline chromosomes into 36 somatic ones, induces specific compartmentalization changes. Parascaris PDE generates the same set of 36 somatic chromosomes, and the 3D compartment changes following PDE are consistent between the two species. Overall, we suggest that CBRs are associated with the boundaries of distinct 3D genome domains. These domains partition the retained and eliminated DNA into separate spatial compartments. We also demonstrate that following PDE, the 3D genome reorganization of the somatic chromosomes in these nematodes is evolutionarily and developmentally conserved.