Defective satellite DNA clustering into chromocenters underlies hybrid incompatibility in Drosophila

Although rapid evolution of pericentromeric satellite DNA repeats is theorized to promote hybrid incompatibility (HI)(1-4), how divergent repeats affect hybrid cells remains poorly understood. Recently, we demonstrated that sequence-specific DNA-binding proteins cluster satellite DNA from multiple chromosomes into chromocenters, thereby bundling chromosomes to maintain the entire genome in a single nucleus(5, 6). Here we show that ineffective clustering of divergent satellite DNA in the cells of Drosophila hybrids results in chromocenter disruption, associated micronuclei formation and tissue atrophy. We further demonstrate that previously identified HI factors trigger chromocenter disruption and micronuclei in hybrids, linking their function to a conserved cellular process. Together, we propose a unifying framework that explains how the widely observed satellite DNA divergence between closely related species can cause reproductive isolation.