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 forward, individual-based simulations to examine the evolution of small-RNA-mediated TE regulation, a conserved mechanism for TE repression that is employed by both prokaryotes and eukaryotes. To design and parameterize a biologically realistic model, we drew on an extensive survey of empirical studies of the transposition and regulation of P -element DNA transposons in Drosophila melanogaster . 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 in simulated populations. We further show that the spread of repressor alleles through simulated populations is greatly enhanced by two additional TE-imposed fitness costs: dysgenic sterility and ectopic recombination. Finally, we demonstrate that the adaptive mutation rate to repression is a critical parameter that influences both the evolutionary trajectory of host repression and the associated proliferation of TEs after invasion in simulated populations. Our findings suggest that adaptive evolution of TE regulation may be stronger and more prevalent than previously appreciated, and provide a framework for interpreting empirical data.

The evolutionary arms race between transposable elements and piRNAs in Drosophila melanogaster

“…Our results suggest that piR-NAs can significantly reduce the fitness cost of TEs, and that TE insertions that generate piRNAs are favored by natural selection [99]. Similar conclusions were drawn by other studies as well [102,103]. Since piRNAs suppress activities of the target TEs, one might intuitively expect to observe a negative correlation between the copy numbers/activities of TEs and piRNAs at the population level.…”

Rapid evolution of piRNA-mediated silencing of an invading transposable element was driven by abundant de novo mutations

“…S3; Supplemental Table S7). P-element insertions into ancestral piRNA clusters are proposed to benefit the host by preventing the accumulation of additional deleterious insertions, suppressing dysgenic sterility, and potentially establishing heterochromatin formation at P-element loci that suppresses their participation in ectopic recombination (Charlesworth and Langley 1986;Lee and Langley 2012;Kelleher et al 2018). To detect a signature of positive selection on P-element insertion alleles in ancestral piRNA clusters, we compared the frequencies of these putatively beneficial alleles to those of neutral or deleterious P-element insertions that do not establish repression.…”

“…After invasion, repressor alleles are proposed to arise through de novo mutation, when an invading TE copy randomly inserts into a piRNA-producing locus referred to as a piRNA cluster (Girard and Hannon 2008;Khurana et al 2011). The existence of numerous alternative piRNA clusters-for example, 142 loci or ∼3.5% of assembled Drosophila melanogaster genome based on Brennecke et al 2007-may facilitate the evolution of repression by increasing the probability that a random insertion occurs in a piRNA-producing site (Kelleher 2016;Kelleher et al 2018;Kofler 2019). However, the technical challenge of annotating polymorphic TE insertions in repeat-rich piRNA clusters has limited the identification and study of these repressor alleles.…”

“…Additionally, although selection for repression may be strong when the genome is invaded by a new TE family, it is unclear whether it is sustained for a sufficient number of generations to enact meaningful changes in repressor allele frequency (Lee and Langley 2012). On the other hand, forward simulation models suggest that piRNA-mediated repressor alleles are targets of positive selection, especially when transposition rates are high and TEs are highly deleterious (Lu and Clark 2010;Kelleher et al 2018;Kofler 2019). Moreover, an early population genomic analysis of D. melanogaster suggests that TE insertions in piRNA clusters may segregate at higher frequency than noncluster insertions, although this is based on modest sample size and read depth (Lu and Clark 2010).…”

Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways

“…Both recent and early studies demonstrated a positive correlation between hybrid dysgenesis severity and P-element copy number [ 2 , 3 , 225 , 232 ], however, others report a weak [ 233 ] or lack of correlation [ 234 , 235 , 236 ]. The discrepancy may be due to species-specific differences, intraspecies genetic differences, P-element structural variation, or piRNA cluster size [ 234 , 237 , 238 , 239 ].…”