Transposable Elements Families Research Articles

Transposon dynamics in the emerging oilseed crop Thlaspi arvense.

Genome evolution is partly driven by the mobility of transposable elements (TEs) which often leads to deleterious effects, but their activity can also facilitate genetic novelty and catalyze local adaptation. We explored how the intraspecific diversity of TE polymorphisms might contribute to the broad geographic success and adaptive capacity of the emerging oil crop Thlaspi arvense (field pennycress). We classified the TE inventory based on a high-quality genome assembly, estimated the age of retrotransposon TE families and comprehensively assessed their mobilization potential. A survey of 280 accessions from 12 regions across the Northern hemisphere allowed us to quantify over 90,000 TE insertion polymorphisms (TIPs). Their distribution mirrored the genetic differentiation as measured by single nucleotide polymorphisms (SNPs). The number and types of mobile TE families vary substantially across populations, but there are also shared patterns common to all accessions. Ty3/Athila elements are the main drivers of TE diversity in T. arvense populations, while a single Ty1/Alesia lineage might be particularly important for transcriptome divergence. The number of retrotransposon TIPs is associated with variation at genes related to epigenetic regulation, including an apparent knockout mutation in BROMODOMAIN AND ATPase DOMAIN-CONTAINING PROTEIN 1 (BRAT1), while DNA transposons are associated with variation at the HSP19 heat shock protein gene. We propose that the high rate of mobilization activity can be harnessed for targeted gene expression diversification, which may ultimately present a toolbox for the potential use of transposition in breeding and domestication of T. arvense.

Significant Variations in Double-Stranded RNA Levels in Cultured Skin Cells.

Endogenous double-stranded RNA has emerged as a potent stimulator of innate immunity. Under physiological conditions, endogenous dsRNA is maintained in the cell nucleus or the mitochondria; however, if protective mechanisms are breached, it leaches into the cytoplasm and triggers immune signaling pathways. Ectopic activation of innate immune pathways is associated with various diseases and senescence and can trigger apoptosis. Hereby, the level of cytoplasmic dsRNA is crucial. We have enriched dsRNA from two melanoma cell lines and primary dermal fibroblasts, including a competing probe, and analyzed the dsRNA transcriptome using RNA sequencing. There was a striking difference in read counts between the cell lines and the primary cells, and the effect was confirmed by northern blotting and immunocytochemistry. Both mitochondria (10-20%) and nuclear transcription (80-90%) contributed significantly to the dsRNA transcriptome. The mitochondrial contribution was lower in the cancer cells compared to fibroblasts. The expression of different transposable element families was comparable, suggesting a general up-regulation of transposable element expression rather than stimulation of a specific sub-family. Sequencing of the input control revealed minor differences in dsRNA processing pathways with an upregulation of oligoadenylate synthase and RNP125 that negatively regulates the dsRNA sensors RIG1 and MDA5. Moreover, RT-qPCR, Western blotting, and immunocytochemistry confirmed the relatively minor adaptations to the hugely different dsRNA levels. As a consequence, these transformed cell lines are potentially less tolerant to interventions that increase the formation of endogenous dsRNA.

Transposon Removal Reveals Their Adaptive Fitness Contribution.

Transposable elements are molecular parasites that persist in their host genome by generating new copies to outpace natural selection. Transposable elements exert a large influence on host genome evolution, in some cases providing adaptive changes. Here we measure the fitness effect of the transposable element insertions in the fission yeast Schizosaccharomyces pombe type strain by removing all insertions of its only native transposable element family, the long terminal repeat retrotransposon Tf2. We show that Tf2 elements provide a positive fitness contribution to its host. Tf2 ablation results in changes to the regulation of a mitochondrial gene and, consistently, the fitness effect are sensitive to growth conditions. We propose that Tf2 influences host fitness in a directed manner by dynamically rewiring the transcriptional response to metabolic stress.

Molecular identification of polymorphic transposable elements in populations of the invasive ant Cardiocondyla obscurior.

Transposable elements (TEs) are found in virtually every eukaryotic genome and are important for generating de novo genetic variation. However, outside of costly and time-consuming whole-genome sequencing approaches, the set of available methods to study TE polymorphisms in non-model species is very limited. The Transposon Display (TD) is a simple yet effective technique to characterize polymorphisms across samples by identifying amplified fragment length polymorphisms using primers targeting specific TE families. So far, this technique has almost exclusively been used in plants. Here, we present an optimized TD protocol for insect species with small genomes such as ants (ca. 200-600 Mb). We characterized TE polymorphisms between two distinct genetic lineages of the invasive ant Cardiocondyla obscurior, as well as between neighboring populations of the New World lineage. We found active LTR/Ty3 retrotransposons, that contributed to the genetic diversification of populations in this species.

The Genomic Shock Hypothesis: Genetic and Epigenetic Alterations of Transposable Elements after Interspecific Hybridization in Plants.

Transposable elements (TEs) are major components of plant genomes with the ability to change their position in the genome or to create new copies of themselves in other positions in the genome. These can cause gene disruption and large-scale genomic alterations, including inversions, deletions, and duplications. Host organisms have evolved a set of mechanisms to suppress TE activity and counter the threat that they pose to genome integrity. These includes the epigenetic silencing of TEs mediated by a process of RNA-directed DNA methylation (RdDM). In most cases, the silencing machinery is very efficient for the vast majority of TEs. However, there are specific circumstances in which TEs can evade such silencing mechanisms, for example, a variety of biotic and abiotic stresses or in vitro culture. Hybridization is also proposed as an inductor of TE proliferation. In fact, the discoverer of the transposons, Barbara McClintock, first hypothesized that interspecific hybridization provides a "genomic shock" that inhibits the TE control mechanisms leading to the mobilization of TEs. However, the studies carried out on this topic have yielded diverse results, showing in some cases a total absence of mobilization or being limited to only some TE families. Here, we review the current knowledge about the impact of interspecific hybridization on TEs in plants and the possible implications of changes in the epigenetic mechanisms.

The successive emergence ofERVL-MaLRs inprimates.

Although the ERVL-mammalian-apparent LTR retrotransposons (MaLRs) are the fourth largest family of transposable elements in the human genome, their evolutionary history and relationship have not been thoroughly studied. In this study, through RepeatMasker annotations of some representative species and construction of phylogenetic tree by sequence similarity, all primate-specific MaLR members are found to descend from MLT1A1 retrotransposon. Comparative genomic analysis, transposition-in-transposition inference, and sequence feature comparisons consistently show that each MaLR member evolved from its predecessor successively and had a limited activity period during primate evolution. Accordingly, a novel MaLR member was discovered as successor of MSTB1 in Tarsiiformes. At last, the identification of candidate precursor and intermediate THE1A elements provides further evidence for the previously proposed arms race model between ZNF430/ZNF100 and THE1B/THE1A. Taken together, this study sheds light on the evolutionary history of MaLRs and can serve as a foundation for future research on their interactions with zinc finger genes, gene regulation, and human health implications.

Selective control of transposable element expression during T cell exhaustion and anti-PD-1 treatment.

In chronic infections and cancer, T cells are exposed to prolonged antigen stimulation, resulting in loss of function (or exhaustion) and impairment of effective immunological protection. Exhausted T cells are heterogeneous and include early progenitors (Tpex) and terminally exhausted cells (Tex). Here, we used bulk and single-cell transcriptomics to analyze expression of transposable elements (TEs) in subpopulations of mouse and human CD8+ tumor-infiltrating T lymphocytes (TILs). We show that in mice, members of the virus-like murine VL30 TE family (mostly intact, evolutionary young ERV1s) are strongly repressed in terminally exhausted CD8+ T cells in both tumor and viral models of exhaustion. Tpex expression of these VL30s, which are mainly intergenic and transcribed independently of their closest gene neighbors, was driven by Fli1, a transcription factor involved in progression from Tpex to Tex. Immune checkpoint blockade (ICB) in both mice and patients with cancer increased TE expression (including VL30 in mice), demonstrating that TEs may be applicable as ICB response biomarkers. We conclude that expression of TEs is tightly regulated in TILs during establishment of exhaustion and reprogramming by ICB. Analyses of TE expression on single cells and bulk populations open opportunities for understanding immune cell identity and heterogeneity, as well as for defining cellular gene expression signatures and disease biomarkers.

The composition of piRNA clusters in Drosophila melanogaster deviates from expectations under the trap model

BackgroundIt is widely assumed that the invasion of a transposable element (TE) in mammals and invertebrates is stopped when a copy of the TE jumps into a piRNA cluster (i.e., the trap model). However, recent works, which for example showed that deletion of three major piRNA clusters has no effect on TE activity, cast doubt on the trap model.ResultsHere, we test the trap model from a population genetics perspective. Our simulations show that the composition of regions that act as transposon traps (i.e., potentially piRNA clusters) ought to deviate from regions that have no effect on TE activity. We investigated TEs in five Drosophila melanogaster strains using three complementary approaches to test whether the composition of piRNA clusters matches these expectations. We found that the abundance of TE families inside and outside of piRNA clusters is highly correlated, although this is not expected under the trap model. Furthermore, the distribution of the number of TE insertions in piRNA clusters is also much broader than expected.ConclusionsWe found that the observed composition of piRNA clusters is not in agreement with expectations under the simple trap model. Dispersed piRNA producing TE insertions and temporal as well as spatial heterogeneity of piRNA clusters may account for these deviations.

Impact of heat stress on Transposable Element expression and derived small RNAs in Drosophila subobscura.

Global warming is forcing insect populations to move and adapt, triggering adaptive genetic responses. Thermal stress is known to alter gene expression, repressing the transcription of active genes, and inducing others, such as those encoding heat shock proteins. It has also been related to the activation of some specific Transposable Element (TE) families. However, the actual magnitude of this stress on the whole genome and the factors involved in these genomic changes are still unclear. We studied mRNAs and small RNAs in gonads of two Drosophila subobscura populations, considered a good model to study adaptation to temperature changes. In control conditions, we found that a few genes and TE families were differentially expressed between populations, pointing out their putative involvement in the adaptation of populations to their different environments. Under heat stress, sex specific changes in gene expression together with a trend towards overexpression, mainly of heat shock response-related genes were observed. We did not observe large changes of TE expression nor small RNA production due to stress. Only population and sex-specific expression changes of some TE families (mainly retrotransposons), or the amounts of siRNAs and piRNAs, derived from specific TE families were observed, as well as the piRNA production from some piRNA clusters. Changes in small RNA amounts and TE expression could not be clearly correlated, indicating that other factors as chromatin modulation, could also be involved. This work provides the first whole transcriptomic study including genes, TEs and small RNAs after a heat stress in D. subobscura.

Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation

BackgroundVitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells.ResultsHere we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism.ConclusionVitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function.

The impact of paramutations on the invasion dynamics of transposable elements.

According to the prevailing view, the trap model, the activity of invading transposable elements (TEs) is greatly reduced when a TE copy jumps into a piRNA cluster, which triggers the emergence of piRNAs that silence the TE. One crucial component in the host defence are paramutations. Mediated by maternally deposited piRNAs, paramutations convert TE insertions into piRNA producing loci, thereby transforming selfish TEs into agents of the host defence. Despite this significant effect, the impact of paramutations on the dynamics of TE invasions remains unknown. To address this issue, we performed extensive forward simulations of TE invasions with piRNA clusters and paramutations. We found that paramutations significantly affect TE dynamics, by accelerating the silencing of TE invasions, reducing the number of insertions accumulating during the invasions and mitigating the fitness cost of TEs. We also demonstrate that piRNA production induced by paramutations, an epigenetically inherited trait, may be positively selected. Finally, we show that paramutations may account for three important open problems with the trap model. Firstly, paramutated TE insertions may compensate for the insufficient number of insertions in piRNA clusters observed in previous studies. Secondly, paramutations may explain the discrepancy between the observed and the expected abundance of different TE families in Drosophila melanogaster. Thirdly, piRNA clusters may be crucial to trigger the host defence, but paramutations render the clusters dispensable once the defence has been established. This could account for the lack of TE activation when three major piRNA clusters were deleted in a previous study.

The blackcap (Sylvia atricapilla) genome reveals a recent accumulation of LTR retrotransposons

Transposable elements (TEs) are mobile genetic elements that can move around the genome, and as such are a source of genomic variability. Based on their characteristics we can annotate TEs within the host genome and classify them into specific TE types and families. The increasing number of available high-quality genome references in recent years provides an excellent resource that will enhance the understanding of the role of recently active TEs on genetic variation and phenotypic evolution. Here we showcase the use of a high-quality TE annotation to understand the distinct effect of recent and ancient TE insertions on the evolution of genomic variation, within our study species the Eurasian blackcap (Sylvia atricapilla). We investigate how these distinct TE categories are distributed along the genome and evaluate how their coverage across the genome is correlated with four genomic features: recombination rate, gene coverage, CpG island coverage and GC content. We found within the recent TE insertions an accumulation of LTRs previously not seen in birds. While the coverage of recent TE insertions was negatively correlated with both GC content and recombination rate, the correlation with recombination rate disappeared and turned positive for GC content when considering ancient TE insertions.

Deciphering shared attributes of plant long non-coding RNAs through a comparative computational approach

Over the past decade, long non-coding RNA (lncRNA), which lacks protein-coding potential, has emerged as an essential regulator of the genome. The present study examined 13,599 lncRNAs in Arabidopsis thaliana, 11,565 in Oryza sativa, and 32,397 in Zea mays for their characteristic features and explored the associated genomic and epigenomic features. We found lncRNAs were distributed throughout the chromosomes and the Helitron family of transposable elements (TEs) enriched, while the terminal inverted repeat depleted in lncRNA transcribing regions. Our analyses determined that lncRNA transcribing regions show rare or weak signals for most epigenetic marks except for H3K9me2 and cytosine methylation in all three plant species. LncRNAs showed preferential localization in the nucleus and cytoplasm; however, the distribution ratio in the cytoplasm and nucleus varies among the studied plant species. We identified several conserved endogenous target mimic sites in the lncRNAs among the studied plants. We found 233, 301, and 273 unique miRNAs, potentially targeting the lncRNAs of A. thaliana, O. sativa, and Z. mays, respectively. Our study has revealed that miRNAs, which interact with lncRNAs, target genes that are involved in a diverse array of biological and molecular processes. The miRNA-targeted lncRNAs displayed a strong affinity for several transcription factors, including ERF and BBR-BPC, mutually present in all three plants, advocating their conserved functions. Overall, the present study showed that plant lncRNAs exhibit conserved genomic and epigenomic characteristics and potentially govern the growth and development of plants.

Downregulation of transposable elements extends lifespan in Caenorhabditis elegans

Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.

Impacts of Sex Ratio Meiotic Drive on Genome Structure and Function in a Stalk-Eyed Fly.

Stalk-eyed flies in the genus Teleopsis carry selfish genetic elements that induce sex ratio (SR) meiotic drive and impact the fitness of male and female carriers. Here, we assemble and describe a chromosome-level genome assembly of the stalk-eyed fly, Teleopsis dalmanni, to elucidate patterns of divergence associated with SR. The genome contains tens of thousands of transposable element (TE) insertions and hundreds of transcriptionally and insertionally active TE families. By resequencing pools of SR and ST males using short and long reads, we find widespread differentiation and divergence between XSR and XST associated with multiple nested inversions involving most of the SR haplotype. Examination of genomic coverage and gene expression data revealed seven X-linked genes with elevated expression and coverage in SR males. The most extreme and likely drive candidate involves an XSR-specific expansion of an array of partial copies of JASPer, a gene necessary for maintenance of euchromatin and associated with regulation of TE expression. In addition, we find evidence for rapid protein evolution between XSR and XST for testis expressed and novel genes, that is, either recent duplicates or lacking a Dipteran ortholog, including an X-linked duplicate of maelstrom, which is also involved in TE silencing. Overall, the evidence suggests that this ancient XSR polymorphism has had a variety of impacts on repetitive DNA and its regulation in this species.

Transposons contribute to the acquisition of cell type-specific cis-elements in the brain

Mammalian brains have evolved in stages over a long history to acquire higher functions. Recently, several transposable element (TE) families have been shown to evolve into cis-regulatory elements of brain-specific genes. However, it is not fully understood how TEs are important for gene regulatory networks. Here, we performed a single-cell level analysis using public data of scATAC-seq to discover TE-derived cis-elements that are important for specific cell types. Our results suggest that DNA elements derived from TEs, MER130 and MamRep434, can function as transcription factor-binding sites based on their internal motifs for Neurod2 and Lhx2, respectively, especially in glutamatergic neuronal progenitors. Furthermore, MER130- and MamRep434-derived cis-elements were amplified in the ancestors of Amniota and Eutheria, respectively. These results suggest that the acquisition of cis-elements with TEs occurred in different stages during evolution and may contribute to the acquisition of different functions or morphologies in the brain.

Genomics of cold adaptations in the Antarctic notothenioid fish radiation

Numerous novel adaptations characterise the radiation of notothenioids, the dominant fish group in the freezing seas of the Southern Ocean. To improve understanding of the evolution of this iconic fish group, here we generate and analyse new genome assemblies for 24 species covering all major subgroups of the radiation, including five long-read assemblies. We present a new estimate for the onset of the radiation at 10.7 million years ago, based on a time-calibrated phylogeny derived from genome-wide sequence data. We identify a two-fold variation in genome size, driven by expansion of multiple transposable element families, and use the long-read data to reconstruct two evolutionarily important, highly repetitive gene family loci. First, we present the most complete reconstruction to date of the antifreeze glycoprotein gene family, whose emergence enabled survival in sub-zero temperatures, showing the expansion of the antifreeze gene locus from the ancestral to the derived state. Second, we trace the loss of haemoglobin genes in icefishes, the only vertebrates lacking functional haemoglobins, through complete reconstruction of the two haemoglobin gene clusters across notothenioid families. Both the haemoglobin and antifreeze genomic loci are characterised by multiple transposon expansions that may have driven the evolutionary history of these genes.

All families of transposable elements were active in the recent wheat genome evolution and polyploidy had no impact on their activity.

Bread wheat (Triticum aestivum L.) is a major crop and its genome is one of the largest ever assembled at reference-quality level. It is 15Gb, hexaploid, with 85% of transposable elements (TEs). Wheat genetic diversity was mainly focused on genes and little is known about the extent of genomic variability affecting TEs, transposition rate, and the impact of polyploidy. Multiple chromosome-scale assemblies are now available for bread wheat and for its tetraploid and diploid wild relatives. In this study, we computed base pair-resolved, gene-anchored, whole genome alignments of A, B, and D lineages at different ploidy levels in order to estimate the variability that affects the TE space. We used assembled genomes of 13 T.aestivum cultivars (6x=AABBDD) and a single genome for Triticum durum (4x=AABB), Triticum dicoccoides (4x=AABB), Triticum urartu (2x=AA), and Aegilops tauschii (2x=DD). We show that 5%-34% of the TE fraction is variable, depending on the species divergence. Between 400 and 13,000 novel TE insertions per subgenome were detected. We found lineage-specific insertions for nearly all TE families in di-, tetra-, and hexaploids. No burst of transposition was observed and polyploidization did not trigger any boost of transposition. This study challenges the prevailing idea of wheat TE dynamics and is more in agreement with an equilibrium model of evolution.

Low impact of polyploidization on the transcriptome of synthetic allohexaploid wheat

BackgroundBread wheat is a recent allohexaploid (genomic constitution AABBDD) that emerged through a hybridization between tetraploid Triticum turgidum (AABB) and diploid Aegilops tauschii (DD) less than 10,000 years ago. The hexaploidization can be re-created artificially, producing synthetic wheat that has been used to study immediate genomic responses to polyploidization. The scale of the consequences of polyploidization, and their mechanism of establishment, remain uncertain.ResultsHere we sampled several synthetic wheats from alternative parental genotypes and reciprocal crosses, and examined transcriptomes from two different tissues and successive generations. We did not detect any massive reprogramming in gene expression, with only around 1% of expressed genes showing significant differences compared to their lower-ploidy parents. Most of this differential expression is located on the D subgenome, without consistency in the direction of the expression change. Homoeolog expression bias in synthetic wheat is similar to the pattern observed in the parents. Both differential expression and homoeolog bias are tissue-specific. While up to three families of transposable elements became upregulated in wheat synthetics, their position and distance are not significantly associated with expression changes in proximal genes.DiscussionWhile only a few genes change their expression pattern after polyploidization, they can be involved in agronomically important pathways. Alternative parental combinations can lead to opposite changes on the same subset of D-located genes, which is relevant for harnessing new diversity in wheat breeding. Tissue specificity of the polyploidization-triggered expression changes indicates the remodelling of transcriptomes in synthetic wheat is plastic and likely caused by regulome interactions rather than permanent changes. We discuss the pitfalls of transcriptomic comparisons across ploidy levels that can inflate the de-regulation signal.ConclusionsTranscriptomic response to polyploidization in synthetic AABBDD wheat is modest and much lower than some previous estimates. Homoeolog expression bias in wheat allohexaploids is mostly attributed to parental legacy, with polyploidy having a mild balancing effect.

Transposable elements are associated with the variable response to influenza infection

Influenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Here, we wanted to explore the potential contribution of transposable elements (TEs) to the variable human immune response. Transcriptome profiling in monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation in viral load post-infection. Using transposase-accessible chromatin using sequencing (ATAC-seq), we identified a set of TE families with either enhanced or reduced accessibility upon infection. Of the enhanced families, 15 showed high variability between individuals and had distinct epigenetic profiles. Motif analysis showed an association with known immune regulators (e.g., BATFs, FOSs/JUNs, IRFs, STATs, NFkBs, NFYs, and RELs) in stably enriched families and with other factorsin variable families, including KRAB-ZNFs. We showed that TEs and host factors regulating TEs were predictive of viral load post-infection. Our findings shed light on the role TEs and KRAB-ZNFs may play in inter-individual variation in immunity.