113 Oral - Evolution II
Friday April 08, 4:45 PM - 5:00 PM

Authors:
Cara Brand; Mia Levine

Affiliation: University of Pennsylvania

Keywords:
u. other (coevolution); b. oogenesis

Satellite DNA spans megabases of eukaryotic genome sequence. These vast stretches of tandem DNA repeats undergo high rates of sequence turnover, resulting in radically different satellite DNA landscapes between closely related species. Such extreme evolutionary plasticity suggests that satellite DNA accumulates mutations with no functional consequence. Paradoxically, satellite-rich genomic regions support essential, conserved nuclear processes, including chromosome segregation, dosage compensation, and nuclear structure. A leading resolution to this paradox is that deleterious proliferation of satellite DNA variants trigger adaptive evolution of satellite-associated chromosomal proteins to preserve these essential functions. Here we experimentally test this model of intra-genomic coevolution between chromosomal proteins and DNA satellites by conducting an evolution-guided manipulation of both. The 359bp satellite spans an 11Mb array in D. melanogaster that is absent from its sister species, D. simulans. This species-specific satellite array colocalizes with the Drosophila protein, Maternal Haploid (MH), an essential, adaptively evolving member of the Spartan family of proteases that cleave DNA-protein crosslinks. To determine if MH and 359 coevolve, we swapped the D. simulans version of MH (“MH[sim]”) into D. melanogaster. We discovered that MH[sim] triggers elevated ovarian cell death, reduced ovary size, and loss of mature eggs. In contrast, mh null females have no such ovary phenotypes, suggesting that MH[sim] is toxic. Using both cell biological and genetic approaches, we demonstrate that MH[sim] poisons oogenesis through a DNA damage pathway. Remarkably, deleting the D. melanogaster-specific 359 satellite array from mh[sim] females completely restores female germline genome integrity and fertility, consistent with a history of coevolution between these two fast-evolving components of the Drosophila genome. Genome integrity and female fertility are also restored by overexpressing Topoisomerase II (Top2). Top2 resolves DNA entanglements by generating transient double stranded breaks while crosslinked to DNA. Intriguingly, these DNA-Top2 crosslinks are resolved by the MH homolog in worms and humans. We propose that MH[sim] prematurely cleaves DNA-Top2 crosslinks that form during Top2-mediated processing of 359 entanglements. Under this model, MH evolved adaptively along the D. melanogaster lineage to avoid 359 in the ovary, leading to the observed cross-species incompatibility between the 359 satellite and MH. Our study offers rare experimental evidence that intra-genomic coevolution between ostensibly inert repetitive DNA and essential chromatin proteins preserves germline genome integrity.