Natural variation of piRNA expression affects immunity to transposable elements

Abstract

In the Drosophila germline, transposable elements (TEs) are silenced by PIWI-interacting RNA (piRNA) that originate from distinct genomic regions termed piRNA clusters and are processed by PIWI-subfamily Argonaute proteins. Here, we explore the variation in the ability to restrain an alien TE in different Drosophila strains. The I-element is a retrotransposon involved in the phenomenon of I-R hybrid dysgenesis in Drosophila melanogaster. Genomes of R strains do not contain active I-elements, but harbour remnants of ancestral I-related elements. The permissivity to I-element activity of R females, called reactivity, varies considerably in natural R populations, indicating the existence of a strong natural polymorphism in defense systems targeting transposons. To reveal the nature of such polymorphisms, we compared ovarian small RNAs between R strains with low and high reactivity and show that reactivity negatively correlates with the ancestral I-element-specific piRNA content. Analysis of piRNA clusters containing remnants of I-elements shows increased expression of the piRNA precursors and enrichment by the Heterochromatin Protein 1 homolog, Rhino, in weak R strains, which is in accordance with stronger piRNA expression by these regions. To explore the nature of the differences in piRNA production, we focused on two R strains, weak and strong, and showed that the efficiency of maternal inheritance of piRNAs as well as the I-element copy number are very similar in both strains. At the same time, germline and somatic uni-strand piRNA clusters generate more piRNAs in strains with low reactivity, suggesting the relationship between the efficiency of primary piRNA production and variable response to TE invasions. The strength of adaptive genome defense is likely driven by naturally occurring polymorphisms in the rapidly evolving piRNA pathway proteins. We hypothesize that hyper-efficient piRNA production is contributing to elimination of a telomeric retrotransposon HeT-A, which we have observed in one particular transposon-resistant R strain.

Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus

“…localization and transposition machinery may simplify their regulation by the genome. We observed expansions of all HeT-A subfamilies and TAHRE, but not the TART elements in the longest telomere strain, which is consistent with HeT-A being more sensitive to piRNA repression than TART as suggested by [70]. Similarly, we found that TART elements are segregated from HeT-A family elements and TAHRE in the telomere.…”

Epigenetic Requirements for Triggering Heterochromatinization and Piwi-Interacting RNA Production from Transgenes in the Drosophila Germline

“…The R strain w K , which was used for the I-TG transgenesis, is a strong reactive strain, meaning that a very high level of I-element transposition was observed when introducing functional I-elements by a cross between w K females and inducer males. In w K ovaries, only a minimal amount of ancestral I-derived piRNAs is produced [19,24,40] (Tables S3 and S4). One could argue that initially, the chromatin structure and piRNA production from the I-transgenes in all strains were the same, although later, in the course of the strain-specific history, the transgenes in the 2.1 s and 2.4 s strains became stronger, which resulted in higher Rhi occupancy and more efficient piRNA production.…”

“…We found that the increase in the level of piRNAs targeting I-TG transgenes does not stimulate additional changes of the chromatin state or piRNA production by the transgenes. The study of paternal transgene inheritance by crossing transgenic males with w K females whose oocyte cytoplasm is the poorest in I-specific piRNAs [24] suggests that heterochromatinization and piRNA production at the target locus are activated by a minimum threshold level of complementary piRNAs.…”

Key role of piRNAs in telomeric chromatin maintenance and telomere nuclear positioning inDrosophilagermline

“…Thus, the telomeres need to produce both the intact TE mRNA required for telomere elongation, as well as piRNAs that target these TE mRNA in order to regulate optimal telomere length. Indeed, altering this balance can lead to disruption of telomere length control (3,33).…”