The Evolution of Small-RNA-Mediated Silencing of an Invading Transposable Element

Abstract

Transposable elements (TEs) are genomic parasites that impose fitness costs on their hosts by producing deleterious mutations and disrupting gametogenesis. Host genomes avoid these costs by regulating TE activity, particularly in germline cells where new insertions are heritable and TEs are exceptionally active. However, the capacity of different TE-associated fitness costs to select for repression in the host, and the role of selection in the evolution of TE regulation more generally, remain controversial. In this study, we use individual-based simulations to examine the evolution of TE regulation through small RNA-mediated silencing. Small RNA silencing is a common mechanism for TE regulation employed by both prokaryotes and eukaryotes. We observed that even under conservative assumptions, where small RNA-mediated regulation reduces transposition only, repression evolves rapidly and adaptively after the genome is invaded by a new TE. We further show that the spread of repressor alleles is greatly enhanced by two additional TE-imposed fitness costs: dysgenic sterility and ectopic recombination. Finally, we demonstrate that the mutation rate to repression (i.e., the size of the mutational target) is a critical parameter that influences both the evolutionary trajectory of host repression and the associated proliferation of TEs. Our findings suggest that adaptive evolution of TE regulation may be stronger and more prevalent than previously suggested, and complement recent empirical observations of positive selection on small RNA-mediated repressor alleles. Both prokaryotic and eukaryotic genomes minimize the fitness costs of TEs by controlling their activity through small RNA mediated silencing (reviewed in Blumenstiel 2011). In eukaryotic germlines, small RNA mediated silencing of TEs is enacted by Argonaute proteins that are found in complex with small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). Regulatory siRNAs and piRNAs are produced from anti-sense TE transcripts, and identify TE-derived mRNAs by base complementarity. Complexed Argonaute proteins then silence the targeted TE transcriptionally by inducing heterochromatin formation, or post-transcriptionally by degrading the transcript. Consistent with prevention of germline DNA damage, small RNA-mediated silencing suppresses TE-associated dysgenic sterility in Drosophila (Blumenstiel and Hartl 2005;Brennecke et al. 2008;Chambeyron et al. 2008;Rozhkov et al.

piRNA clusters need a minimum size to control transposable element invasions

“…If individuals with large clusters end up with fewer deleterious TE insertions than individuals with small clusters, large clusters may be positively selected. This hypothesis is supported by recent simulation studies which found that TE insertions within piRNA clusters may be positively selected (Lu and Clark, 2009;Kofler, 2019;Kelleher et al, 2018). Large clusters will on the average end up with more TE insertions than small cluster.…”

“…Fifth, piRNA cluster are mostly composed of TE sequences (Brennecke et al, 2007), supporting the view that clusters carry the trapped remnants of past TE invasions. Sixth, computer simulations confirm that genomic traps, such as piRNA clusters, may stop TE invasions (Kofler, 2019;Kelleher et al, 2018;Lu and Clark, 2009).…”

“…Furthermore a study directly observing TE invasions noted a rapid emergence of piRNA cluster insertions and piRNAs complimentary to the invading TE (Kofler et al, 2018). Finally computer simulations confirmed that piRNA clusters may stop TE invasions (Kelleher et al, 2018;Kofler, 2019;Lu and Clark, 2009). Especially large clusters were able to control TE invasions under a wide range of different conditions (Kofler, 2019).…”

“…There is little doubt about our assumption that TEs multiply within host genomes (Burt and Trivers, 2008;Wicker et al, 2007). However, we also relied on the widely used assumption that the transposition rate is constant during an invasion (in the absence of piRNAs) (Charlesworth and Charlesworth, 1983;Charlesworth, 1991;Kelleher et al, 2018;Lu and Clark, 2009;Kofler, 2019). It is not entirely clear if this assumption holds since very few studies estimated transposition rates during TE invasions.…”

Generating high quality assemblies for genomic analysis of transposable elements

“…Most importantly, however, high-quality assemblies will allow us to study the evolution of piRNA clusters. We could, for example, test the hypothesis that the composition of piRNA clusters evolves rapidly, as expected under the widely held trap model (Kelleher et al, 2018;Kofler, 2019). Long-read based assemblies may thus revolutionize TE research.…”