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1. Off-target piRNA gene silencing in Drosophila melanogaster rescued by a transposable element insertion

   https://doi.org/10.1371/journal.pgen.1010598  

   Miller, Danny E.; Dorador, Ana P.; Van Vaerenberghe, Kelley; Li, Angela; Grantham, Emily K.; Cerbin, Stefan; Cummings, Celeste; Barragan, Marilyn; Egidy, Rhonda R.; Scott, Allison R.; et al (February 2023, PLOS Genetics)

   Bosco, Giovanni (Ed.)

   Transposable elements (TE) are selfish genetic elements that can cause harmful mutations. In Drosophila , it has been estimated that half of all spontaneous visible marker phenotypes are mutations caused by TE insertions. Several factors likely limit the accumulation of exponentially amplifying TEs within genomes. First, synergistic interactions between TEs that amplify their harm with increasing copy number are proposed to limit TE copy number. However, the nature of this synergy is poorly understood. Second, because of the harm posed by TEs, eukaryotes have evolved systems of small RNA-based genome defense to limit transposition. However, as in all immune systems, there is a cost of autoimmunity and small RNA-based systems that silence TEs can inadvertently silence genes flanking TE insertions. In a screen for essential meiotic genes in Drosophila melanogaster , a truncated Doc retrotransposon within a neighboring gene was found to trigger the germline silencing of ald , the Drosophila Mps1 homolog, a gene essential for proper chromosome segregation in meiosis. A subsequent screen for suppressors of this silencing identified a new insertion of a Hobo DNA transposon in the same neighboring gene. Here we describe how the original Doc insertion triggers flanking piRNA biogenesis and local gene silencing. We show that this local gene silencing occurs in cis and is dependent on deadlock , a component of the Rhino-Deadlock-Cutoff (RDC) complex, to trigger dual-strand piRNA biogenesis at TE insertions. We further show how the additional Hobo insertion leads to de-silencing by reducing flanking piRNA biogenesis triggered by the original Doc insertion. These results support a model of TE-mediated gene silencing by piRNA biogenesis in cis that depends on local determinants of transcription. This may explain complex patterns of off-target gene silencing triggered by TEs within populations and in the laboratory. It also provides a mechanism of sign epistasis among TE insertions, illuminates the complex nature of their interactions and supports a model in which off-target gene silencing shapes the evolution of the RDC complex. 

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2. Nested likelihood-ratio testing of the nonsynonymous:synonymous ratio suggests greater adaptation in the piRNA machinery of Drosophila melanogaster compared with Drosophila ananassae and Drosophila willistoni , two species with higher repeat content

   https://doi.org/10.1093/g3journal/jkaf017  

   Blumenstiel, Justin P; Kingan, Sarah B; Garrigan, Daniel; Hill, Tom; Vedanayagam, Jeffrey (February 2025, G3: Genes, Genomes, Genetics)

   Kern, A (Ed.)

   Abstract Numerous studies have revealed a signature of strong adaptive evolution in the piwi-interacting RNA (piRNA) machinery of Drosophila melanogaster, but the cause of this pattern is not understood. Several hypotheses have been proposed. One hypothesis is that transposable element (TE) families and the piRNA machinery are co-evolving under an evolutionary arms race, perhaps due to antagonism by TEs against the piRNA machinery. A related, though not co-evolutionary, hypothesis is that recurrent TE invasion drives the piRNA machinery to adapt to novel TE strategies. A third hypothesis is that ongoing fluctuation in TE abundance leads to adaptation in the piRNA machinery that must constantly adjust between sensitivity for detecting new elements and specificity to avoid the cost of off-target gene silencing. Rapid evolution of the piRNA machinery may also be driven independently of TEs, and instead from other functions such as the role of piRNAs in suppressing sex-chromosome meiotic drive. We sought to evaluate the impact of TE abundance on adaptive evolution of the piRNA machinery in D. melanogaster and 2 species with higher repeat content—Drosophila ananassae and Drosophila willistoni. This comparison was achieved by employing a likelihood-based hypothesis testing framework based on the McDonald–Kreitman test. We show that we can reject a faster rate of adaptive evolution in the piRNA machinery of these 2 species. We propose that the high rate of adaptation in D. melanogaster is either driven by a recent influx of TEs that have occurred during range expansion or selection on other functions of the piRNA machinery. 

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3. The PIWI/piRNA response is relaxed in a rodent that lacks mobilizing transposable elements

   https://doi.org/10.1261/rna.078862.121  

   Vandewege, Michael W.; Patt, Roy N.; Merriman, Dana K.; Ray, David A.; Hoffmann, Federico G. (March 2022, RNA)

   Transposable elements (TEs) are genomic parasites that can propagate throughout host genomes. Mammalian genomes are typically dominated by LINE retrotransposons and their associated SINEs, and germline mobilization is a challenge to genome integrity. There are defenses against TE proliferation and the PIWI/piRNA defense is among the most well understood. However, the PIWI/piRNA system has been investigated largely in animals with actively mobilizing TEs and it is unclear how the PIWI/piRNA system functions in the absence of mobilizing TEs. The 13-lined ground squirrel provides the opportunity to examine PIWI/piRNA and TE dynamics within the context of minimal, and possibly nonexistent, TE accumulation. To do so, we compared the PIWI/piRNA dynamics in squirrels to observations from the rabbit and mouse. Despite a lack of young insertions in squirrels, TEs were still actively transcribed at higher levels compared to mouse and rabbit. All three Piwi genes were not expressed, prior to P8 in squirrel testis, and there was little TE expression change with the onset of Piwi expression. We also demonstrated there was not a major expression change in the young squirrel LINE families in the transition from juvenile to adult testis in contrast to young mouse and rabbit LINE families. These observations lead us to conclude that PIWI suppression, was weaker for squirrel LINEs and SINEs and did not strongly reduce their transcription. We speculate that, although the PIWI/piRNA system is adaptable to novel TE threats, transcripts from TEs that are no longer threatening receive less attention from PIWI proteins. 

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4. Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity

   https://doi.org/10.1038/s41467-023-36354-x  

   Sun, Yu H.; Cui, Hongxiao; Song, Chi; Shen, Jiafei Teng; Zhuo, Xiaoyu; Wang, Ruoqiao Huiyi; Yu, Xiaohui; Ndamba, Rudo; Mu, Qian; Gu, Hanwen; et al (December 2023, Nature Communications)

   Abstract Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences. 

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5. Evolutionary Dynamics of the Pericentromeric Heterochromatin in Drosophila virilis and Related Species

   https://doi.org/10.3390/genes12020175  

   Rezvykh, Alexander P.; Funikov, Sergei Yu.; Protsenko, Lyudmila A.; Kulikova, Dina A.; Zelentsova, Elena S.; Chuvakova, Lyubov N.; Blumenstiel, Justin P.; Evgen’ev, Michael B. (February 2021, Genes)

   null (Ed.)

   Pericentromeric heterochromatin in Drosophila generally consists of repetitive DNA, forming the environment associated with gene silencing. Despite the expanding knowledge of the impact of transposable elements (TEs) on the host genome, little is known about the evolution of pericentromeric heterochromatin, its structural composition, and age. During the evolution of the Drosophilidae, hundreds of genes have become embedded within pericentromeric regions yet retained activity. We investigated a pericentromeric heterochromatin fragment found in D. virilis and related species, describing the evolution of genes in this region and the age of TE invasion. Regardless of the heterochromatic environment, the amino acid composition of the genes is under purifying selection. However, the selective pressure affects parts of genes in varying degrees, resulting in expansion of gene introns due to TEs invasion. According to the divergence of TEs, the pericentromeric heterochromatin of the species of virilis group began to form more than 20 million years ago by invasions of retroelements, miniature inverted repeat transposable elements (MITEs), and Helitrons. Importantly, invasions into the heterochromatin continue to occur by TEs that fall under the scope of piRNA silencing. Thus, the pericentromeric heterochromatin, in spite of its ability to induce silencing, has the means for being dynamic, incorporating the regions of active transcription. 

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