Cross-species incompatibility between a DNA satellite and the Drosophila Spartan homolog poisons germline genome integrity

Abstract

Satellite DNA spans megabases of eukaryotic sequence and evolves rapidly.1-6 Paradoxically, satellite-rich genomic regions mediate strictly conserved, essential processes such as chromosome segregation and nuclear structure.7-10 A leading resolution to this paradox posits that satellite DNA and satellite-associated chromosomal proteins coevolve to preserve these essential functions.11 We experimentally test this model of intragenomic coevolution by conducting the first evolution-guided manipulation of both chromosomal protein and DNA satellite. The 359bp satellite spans an 11 Mb array in Drosophila melanogaster that is absent from its sister species, Drosophila simulans.12-14 This species-specific DNA satellite colocalizes with the adaptively evolving, ovary-enriched protein, maternal haploid (MH), the Drosophila homolog of Spartan.15 To determine if MH and 359bp coevolve, we swapped the D.simulans version of MH ("MH[sim]") into D.melanogaster. MH[sim] triggers ovarian cell death, reduced ovary size, and loss of mature eggs. Surprisingly, the D.melanogaster mh-null mutant has no such ovary phenotypes,15 suggesting that MH[sim] is toxic in a D.melanogaster background. Using both cell biology and genetics, we discovered that MH[sim] poisons oogenesis through a DNA-damage pathway. Remarkably, deleting the D.melanogaster-specific 359bp satellite array completely restores mh[sim] germline genome integrity and fertility, consistent with a history of coevolution between these two fast-evolving loci. Germline genome integrity and fertility are also restored by overexpressing topoisomerase II (Top2), suggesting that MH[sim] interferes with Top2-mediated processing of 359bp. The observed 359bp-MH[sim] cross-species incompatibility supports a model under which seemingly inert repetitive DNA and essential chromosomal proteins must coevolve to preserve germline genome integrity.