The evolution of RNAi as a defence against viruses and transposable elements.
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ABSTRACT:
SUBMITTER: Obbard DJ
PROVIDER: S-EPMC2592633 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Virus-derived sequences and transposable elements constitute a substantial portion of many cellular genomes. Recent insights reveal the intimate evolutionary relationship between these sequences and various cellular immune pathways. At the most basic level, superinfection exclusion may be considered a prototypical virus-mediated immune system that has been described in both prokaryotes and eukaryotes. More complex immune mechanisms fully or partially derived from mobile genetic elements include CRISPR-Cas of prokaryotes and the RAG1/2 system of vertebrates, which provide immunological memory of foreign genetic elements and generate antibody and T cell receptor diversity, respectively. In this review, we summarize the current knowledge on the contribution of mobile genetic elements to the evolution of cellular immune pathways. A picture is emerging in which the various cellular immune systems originate from and are spread by viruses and transposable elements. Immune systems likely evolved from simple superinfection exclusion to highly complex defense strategies.
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Project description:In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were probably present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and messenger RNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders and scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.
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Project description:Transposable elements (TEs) are a major source of genome variation across the branches of life. Although TEs may play an adaptive role in their host's genome, they are more often deleterious, and purifying selection is an important factor controlling their genomic loads. In contrast, life history, mating system, GC content, and RNAi pathways have been suggested to account for the disparity of TE loads in different species. Previous studies of fungal, plant, and animal genomes have reported conflicting results regarding the direction in which these genomic features drive TE evolution. Many of these studies have had limited power, however, because they studied taxonomically narrow systems, comparing only a limited number of phylogenetically independent contrasts, and did not address long-term effects on TE evolution. Here, we test the long-term determinants of TE evolution by comparing 42 nematode genomes spanning over 500 million years of diversification. This analysis includes numerous transitions between life history states, and RNAi pathways, and evaluates if these forces are sufficiently persistent to affect the long-term evolution of TE loads in eukaryotic genomes. Although we demonstrate statistical power to detect selection, we find no evidence that variation in these factors influence genomic TE loads across extended periods of time. In contrast, the effects of genetic drift appear to persist and control TE variation among species. We suggest that variation in the tested factors are largely inconsequential to the large differences in TE content observed between genomes, and only by these large-scale comparisons can we distinguish long-term and persistent effects from transient or random changes.
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Project description:Transposable elements are often considered parasitic DNA sequences, able to invade the genome of their host thanks to their self-replicating ability. This colonization process has been extensively studied, both theoretically and experimentally, but their long-term coevolution with the genomes is still poorly understood. In this work, we aim to challenge previous population genetics models by considering features of transposable elements as quantitative, rather than discrete, variables. We also describe more realistic transposable element dynamics by accounting for the variability of the insertion effect, from deleterious to adaptive, as well as mutations leading to a loss of transposition activity and to nonautonomous copies. Individual-based simulations of the behavior of a transposable-element family over several thousand generations show different ways in which active or inactive copies can be maintained for a very long time. Results reveal an unexpected impact of genetic drift on the "junk DNA" content of the genome and strongly question the likelihood of the sustainable long-term stable transposition-selection equilibrium on which numerous previous works were based.
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Project description:BackgroundTransposable elements are increasingly recognized as a source of cis-regulatory variation. Previous studies have revealed that transposons are often bound by transcription factors and some have been co-opted into functional enhancers regulating host gene expression. However, the process by which transposons mature into complex regulatory elements, like enhancers, remains poorly understood. To investigate this process, we examined the contribution of transposons to the cis-regulatory network controlling circadian gene expression in the mouse liver, a well-characterized network serving an important physiological function.ResultsChIP-seq analyses reveal that transposons and other repeats contribute ~ 14% of the binding sites for core circadian regulators (CRs) including BMAL1, CLOCK, PER1/2, and CRY1/2, in the mouse liver. RSINE1, an abundant murine-specific SINE, is the only transposon family enriched for CR binding sites across all datasets. Sequence analyses and reporter assays reveal that the circadian regulatory activity of RSINE1 stems from the presence of imperfect CR binding motifs in the ancestral RSINE1 sequence. These motifs matured into canonical motifs through point mutations after transposition. Furthermore, maturation occurred preferentially within elements inserted in the proximity of ancestral CR binding sites. RSINE1 also acquired motifs that recruit nuclear receptors known to cooperate with CRs to regulate circadian gene expression specifically in the liver.ConclusionsOur results suggest that the birth of enhancers from transposons is predicated both by the sequence of the transposon and by the cis-regulatory landscape surrounding their genomic integration site.
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Project description:Transposable elements (TEs) are repeated DNA sequences that can constitute a substantial part of genomes. Studying TEs' activity, interactions, and accumulation dynamics is thus of major interest to understand genome evolution. Here, we describe the transposition dynamics of cut-and-paste mariner elements during experimental (short- and longer-term) evolution in Drosophila melanogaster Flies with autonomous and nonautonomous mariner copies were introduced in populations containing no active mariner, and TE accumulation was tracked by quantitative PCR for up to 100 generations. Our results demonstrate that (i) active mariner elements are highly invasive and characterized by an elevated transposition rate, confirming their capacity to spread in populations, as predicted by the "selfish-DNA" mechanism; (ii) nonautonomous copies act as parasites of autonomous mariner elements by hijacking the transposition machinery produced by active mariner, which can be considered as a case of hyperparasitism; (iii) this behavior resulted in a failure of active copies to amplify which systematically drove the whole family to extinction in less than 100 generations. This study nicely illustrates how the presence of transposition-competitive variants can deeply impair TE dynamics and gives clues to the extraordinary diversity of TE evolutionary histories observed in genomes.
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Project description:RNA interference (RNAi) is a natural endogenous process by which double-stranded RNA molecules trigger potent and specific gene silencing in eukaryotic cells and is characterized by target RNA cleavage. In mammals, small interfering RNAs (siRNAs) are the trigger molecules of choice and constitute a new class of RNA-based antiviral agents. In an efficient RNAi response, the antisense strand of siRNAs must enter the RNA-induced silencing complex (RISC) in a process mediated by thermodynamic features. In this report, we hypothesize that silent mutations capable of inverting thermodynamic properties can promote resistance to siRNAs. Extensive computational analyses were used to assess whether continuous selective pressure that promotes such mutations could lead to the emergence of viral strains completely resistant to RNAi (i.e., prone to transfer only the sense strands to RISC). Based on our findings, we propose that, although synonymous mutations may produce functional resistance, this strategy cannot be systematically adopted by viruses since the longest RNAi-refractory sequence is only 10 nt long. This finding also suggests that all mRNAs display fluctuating thermodynamic landscapes and that, in terms of thermodynamic features, RNAi is a very efficient antiviral system since there will always be sites susceptible to siRNAs.
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Project description:In Drosophila melanogaster, small RNAs homologous to transposable elements (TEs) are of two types: piRNA (piwi-interacting RNA) with size 23-29nt and siRNA (small interfering RNA) with size 19-22nt. The siRNA pathway is suggested to silence TE activities in somatic tissues based on TE expression profiles, but direct evidence of transposition is lacking. Here we developed an efficient FISH (fluorescence in Situ hybridization) based method for polytene chromosomes from larval salivary glands to reveal new TE insertions. Analysis of the LTR-retrotransposon 297 and the non-LTR retroposon DOC shows that in the argonaut 2 (Ago2) and Dicer 2 (Dcr2) mutant strains, new transposition events are much more frequent than in heterozygous strains or wild type strains. The data demonstrate that the siRNA pathway represses TE transposition in somatic cells. Nevertheless, we found that loss of one functional copy of Ago2 or Dcr2 increases somatic transpositions of the elements at a lower level depending on the genetic background, suggesting a quantitative role for RNAi core components on mutation frequency.
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Project description:RNAi and Polycomb repression play evolutionarily conserved and often coordinated roles in transcriptional silencing. Here, we show that, in the protozoan Tetrahymena thermophila, germline-specific internally eliminated sequences (IESs)-many related to transposable elements (TEs)-become transcriptionally activated in mutants deficient in the RNAi-dependent Polycomb repression pathway. Germline TE mobilization also dramatically increases in these mutants. The transition from noncoding RNA (ncRNA) to mRNA production accompanies transcriptional activation of TE-related sequences and vice versa for transcriptional silencing. The balance between ncRNA and mRNA production is potentially affected by cotranscriptional processing as well as RNAi and Polycomb repression. We posit that interplay between RNAi and Polycomb repression is a widely conserved phenomenon, whose ancestral role is epigenetic silencing of TEs.
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Project description:Horizontal transfer of transposable elements (HTT) is an important process shaping eukaryote genomes, yet very few studies have quantified this phenomenon on a large scale or have evaluated the selective constraints acting on transposable elements (TEs) during vertical and horizontal transmission. Here we screen 307 vertebrate genomes and infer a minimum of 975 independent HTT events between lineages that diverged more than 120 million years ago. HTT distribution greatly differs from null expectations, with 93.7% of these transfers involving ray-finned fishes and less than 3% involving mammals and birds. HTT incurs purifying selection (conserved protein evolution) on all TEs, confirming that producing functional transposition proteins is required for a TE to invade new genomes. In the absence of HTT, DNA transposons appear to evolve neutrally within genomes, unlike most retrotransposons, which evolve under purifying selection. This selection regime indicates that proteins of most retrotransposon families tend to process their own encoding RNA (cis-preference), which helps retrotransposons to persist within host lineages over long time periods.
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