QTL mapping of natural variation reveals that the developmental regulatorbrunoreduces tolerance toP-element transposition in theDrosophilafemale germline

Transposable elements (TEs) are obligate genetic parasites that propagate in host genomes by replicating in germline nuclei, thereby ensuring transmission to offspring. This selfish replication not only produces deleterious mutations---in extreme cases, TE mobilization induces genotoxic stress that prohibits the production of viable gametes. Host genomes could reduce these fitness effects in two ways: resistance and tolerance. Resistance to TE propagation is enacted by germline specific small-RNA-mediated silencing pathways, such as the piRNA pathway, and is studied extensively. However, it remains entirely unknown whether host genomes may also evolve tolerance, by desensitizing gametogenesis to the harmful effects of TEs. In part, the absence of research on tolerance reflects a lack of opportunity, as small-RNA-mediated silencing evolves rapidly after a new TE invades, thereby masking existing variation in tolerance.We have exploited the recent the historical invasion of theDrosophila melanogastergenome byP-element DNA transposons in order to study tolerance of TE activity. In the absence of piRNA-mediated silencing, the genotoxic stress imposed byP-elements disrupts oogenesis, and in extreme cases leads to atrophied ovaries that completely lack germline cells. By performing QTL-mapping on a panel of recombinant inbred lines (RILs) that lack piRNA-mediated silencing ofP-elements, we uncovered multiple QTL that are associated with differences in tolerance of oogenesis toP-element transposition. We localized the most significant QTL to a small 230 Kb euchromatic region, with the LOD peak occurring in theBrunolocus, which codes for a critical and well-studied developmental regulator of oogenesis. We further demonstrate that multiplebrunoloss-of-function alleles are strong dominant suppressors of ovarian atrophy, allowing for the development of mature egg-chambers in the face ofP-element activity. Genetic and cytological analyses suggest thatbrunotolerance is explained by enhanced retention of germline stem cells in dysgenic ovaries, which are typically lost due to DNA damage. Our observations reveal segregating variation in TE tolerance for the first time, and implicate gametogenic regulators as a source of tolerant variants in natural populations.