Abstract
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 Piwi-interacting RNA (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 historical invasion of the Drosophila melanogaster genome by P-element DNA transposons in order to study tolerance of TE activity. In the absence of piRNA-mediated silencing, the genotoxic stress imposed by P-elements disrupts oogenesis and, in extreme cases, leads to atrophied ovaries that completely lack germline cells. By performing quantitative trait locus (QTL) mapping on a panel of recombinant inbred lines (RILs) that lack piRNA-mediated silencing of P-elements, we uncovered multiple QTL that are associated with differences in tolerance of oogenesis to P-element transposition. We localized the most significant QTL to a small 230-kb euchromatic region, with the logarithm of the odds (LOD) peak occurring in the bruno locus, which codes for a critical and well-studied developmental regulator of oogenesis. Genetic, cytological, and expression analyses suggest that bruno dosage modulates germline stem cell (GSC) loss in the presence of P-element activity. 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.
Highlights
Transposable elements (TEs) are omnipresent and abundant constituents of eukaryotic genomes, comprising up to 80% of genomic DNA in some lineages
Transposable elements (TEs), or “jumping genes,” are mobile fragments of selfish DNA that leave deleterious mutations and DNA damage in their wake as they spread through host genomes
We study for the first time whether host cells might exhibit tolerance to TEs, by reducing their harmful effects without directly controlling their movement
Summary
Transposable elements (TEs) are omnipresent and abundant constituents of eukaryotic genomes, comprising up to 80% of genomic DNA in some lineages (reviewed in [1]). In addition to causing deleterious mutations [13,14], TEs can exert lethal, genotoxic effects on host cells by producing abundant double-stranded breaks (DSBs) during insertion and excision [15,16]. Host developmental and evolutionary responses to parasites, pathogens, and herbivores are broadly delineated into two categories: resistance and tolerance (reviewed in [17,18]). Mechanisms of tolerance do not affect propagation but rather limit the fitness costs to the host. Tolerance represents a wholly unexplored arena of the evolutionary dynamics between TEs and their hosts. Germline tolerance of TEs is predicted to be of particular importance because of the significance of this cell lineage in ensuring the vertical transmission of the parasite and the reproductive fitness of the host
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