Mobile DNA最新文献

From April 20 to 23, 2024, three hundred ten researchers from around the world gathered in Saint-Malo, France, at the fourth International Congress on Transposable Elements (ICTE 2024), to present their most recent discoveries on transposable elements (TEs) and exchange ideas and methodologies. ICTE has been held every four years since 2008 (except in 2020, when it was exceptionally transformed into a seminar series due to the Covid-19 pandemic) and is organized by the French network on Mobile Genetic Elements (CNRS GDR 3546). This fourth edition offered two keynote presentations and four sessions presenting the latest findings and encouraging discussions on the following topics: (1) TEs, genome evolution and adaptation; (2) TEs in health and diseases; (3) TE control and epigenetics; (4) Transposition mechanisms and applications. The 2024 edition also included a half-day satellite workshop on new challenges in TE annotation, organized in collaboration with the TE Hub. The meeting gathered long-term TE enthusiasts, as well as newcomers to the field, with 77% of the participants attending ICTE for the first time.

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder, and transposable elements (TEs) have been hypothesized to play a significant role in its development. However, limited research has explored this connection. Our study aimed to examine the relationship between TE expression and SLE pathogenesis.

Methods: We analyzed whole blood RNA-seq datasets from 198 SLE patients and 84 healthy controls. The REdiscoverTE pipeline was employed to quantify TE and other gene expressions, identifying differentially expressed TEs. A TE score was calculated to measure overall TE expression for each sample. Gene ontology and gene set enrichment analyses were conducted to explore the functional implications of TE upregulation. Independent datasets were utilized to replicate the results and investigate cell type-specific TE expression.

Results: Our analysis identified two distinct patient groups: one with high TE expression and another with TE expression comparable to controls. Patients with high TE expression exhibited upregulation of pathways involving nucleic acid sensors, and TE expression was strongly correlated with interferon (IFN) signatures. Furthermore, these patients displayed deregulated cell composition, including increased neutrophils and decreased regulatory T cells. Neutrophils were suggested as the primary source of TE expression, contributing to IFN production.

Conclusions: Our findings suggest that TE expression may serve as a crucial mediator in maintaining the activation of interferon pathways, acting as an endogenous source of nucleic acid stimulators in SLE patients.

Genome annotation is an important but challenging task. Accurate identification of short interspersed nuclear elements (SINEs) is particularly difficult due to their lack of highly conserved sequences. AnnoSINE is state-of-the-art software for annotating SINEs in plant genomes, but it is computationally inefficient for large genomes. Moreover, its applicability to animals is limited due to the absence of animal pHMMs in its HMM library. Therefore, we propose AnnoSINE_v2, which extends accurate SINE annotation for animal genomes with greatly optimized computational efficiency. Our results show that AnnoSINE_v2's annotation of SINEs has over 20% higher F1-score compared to the existing tools on animal genomes and enables the processing of complicated genomes, like human and zebrafish, which were beyond the capabilities of AnnoSINE_v1. AnnoSINE_v2 is freely available on Conda and GitHub: https://github.com/liaoherui/AnnoSINE_v2 .

Background: Short interspersed nuclear elements (SINEs) are non-autonomous non-LTR retrotransposons widespread across eukaryotes. They exist both as lineage-specific, fast-evolving elements and as ubiquitous superfamilies characterized by highly conserved domains (HCD). Several of these superfamilies have been described in bivalves, however their overall distribution and impact on host genome evolution are still unknown due to the extreme scarcity of transposon libraries for the clade. In this study, we examined more than 40 bivalve genomes to uncover the distribution of HCD-tRNA-related SINEs, discover novel SINE-LINE partnerships, and understand their possible role in shaping bivalve genome evolution.

Results: We found that bivalve HCD SINEs have an ancient origin, and they can rely on at least four different LINE clades. According to a "mosaic" evolutionary scenario, multiple LINE partner can promote the amplification of the same HCD SINE superfamilies while homologues LINE-derived tails are present between different superfamilies. Multiple SINEs were found to be highly similar between phylogenetically related species but separated by extremely long evolutionary timescales, up to ~ 400 million years. Studying their genomic distribution in a subset of five species, we observed different patterns of SINE enrichment in various genomic compartments as well as differences in the tendency of SINEs to form tandem-like and palindromic structures also within intronic sequences. Despite these differences, we observed that SINEs, especially older ones, tend to accumulate preferentially within genes, or in their close proximity, consistently with a model of survival bias for less harmful, short non-coding transposons in euchromatic genomic regions.

Conclusion: Here we conducted a wide characterization of tRNA-related SINEs in bivalves revealing their taxonomic distribution and LINE partnerships across the clade. Moreover, through the study of their genomic distribution in five species, we highlighted commonalities and differences with other previously studied eukaryotes, thus extending our understanding of SINE evolution across the tree of life.

Recent studies have suggested that Transposable Elements (TEs) residing in introns frequently splice into and alter primary gene-coding transcripts. To re-examine the exonization frequency of TEs into protein-coding gene transcripts, we re-analyzed a Drosophila neuron circadian rhythm RNAseq dataset and a deep long RNA fly midbrain RNAseq dataset using our Transposon Insertion and Depletion Analyzer (TIDAL) program. Our TIDAL results were able to predict several TE insertions from RNAseq data that were consistent with previous published studies. However, we also uncovered many discrepancies in TE-exonization calls, such as reads that mainly support intron retention of the TE and little support for chimeric mRNA spliced to the TE. We then deployed rigorous genomic DNA-PCR (gDNA-PCR) and RT-PCR procedures on TE-mRNA fusion candidates to see how many of bioinformatics predictions could be validated. By testing a w1118 strain from which the deeper long RNAseq data was derived and comparing to an OreR strain, only 9 of 23 TIDAL candidates (< 40%) could be validated as a novel TE insertion by gDNA-PCR, indicating that deeper study is needed when using RNAseq data as inputs into current TE-insertion prediction programs. Of these validated calls, our RT-PCR results only supported TE-intron retention. Lastly, in the Dscam2 and Bx genes of the w1118 strain that contained intronic TEs, gene expression was 23 times higher than the OreR genes lacking the TEs. This study's validation approach indicates that chimeric TE-mRNAs are infrequent and cautions that more optimization is required in bioinformatics programs to call TE insertions using RNAseq datasets.

Transposable elements (TEs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, in vitro priming of several healthy donors with this epitope of ERV-K-Env did not result in target antigen specificity. These data suggest that the T cell receptor is a poor candidate for targeting this specific ERV-K-Env epitope and has limited potential as a T cell therapy for OC.

Background: Substantial discoveries during the past century have revealed that transposable elements (TEs) can play a crucial role in genome evolution by affecting gene expression and inducing genetic rearrangements, among other molecular and structural effects. Yet, our knowledge on the role of TEs in adaptation to extreme climates is still at its infancy. The availability of long-read sequencing has opened up the possibility to identify and study potential functional effects of TEs with higher precision. In this work, we used Drosophila montana as a model for cold-adapted organisms to study the association between TEs and adaptation to harsh climates.

Results: Using the PacBio long-read sequencing technique, we de novo identified and manually curated TE sequences in five Drosophila montana genomes from eco-geographically distinct populations. We identified 489 new TE consensus sequences which represented 92% of the total TE consensus in D. montana. Overall, 11-13% of the D. montana genome is occupied by TEs, which as expected are non-randomly distributed across the genome. We identified five potentially active TE families, most of them from the retrotransposon class of TEs. Additionally, we found TEs present in the five analyzed genomes that were located nearby previously identified cold tolerant genes. Some of these TEs contain promoter elements and transcription binding sites. Finally, we detected TEs nearby fixed and polymorphic inversion breakpoints.

Conclusions: Our research revealed a significant number of newly identified TE consensus sequences in the genome of D. montana, suggesting that non-model species should be studied to get a comprehensive view of the TE repertoire in Drosophila species and beyond. Genome annotations with the new D. montana library allowed us to identify TEs located nearby cold tolerant genes, and present at high population frequencies, that contain regulatory regions and are thus good candidates to play a role in D. montana cold stress response. Finally, our annotations also allow us to identify for the first time TEs present in the breakpoints of three D. montana inversions.

Rhizobia are alpha- and beta- Proteobacteria that, through the establishment of symbiotic interactions with leguminous plants, are able to fix atmospheric nitrogen as ammonium. The successful establishment of a symbiotic interaction is highly dependent on the availability of nitrogen sources in the soil, and on the specific rhizobia strain. Insertion sequences (ISs) are simple transposable genetic elements that can move to different locations within the host genome and are known to play an important evolutionary role, contributing to genome plasticity by acting as recombination hot-spots, and disrupting coding and regulatory sequences. Disruption of coding sequences may have occurred either in a common ancestor of the species or more recently. By means of ISComapare, we identified Differentially Located ISs (DLISs) in nearly related rhizobial strains of the genera Bradyrhizobium, Mesorhizobium, Rhizobium and Sinorhizobium. Our results revealed that recent IS transposition could have a role in adaptation by enabling the activation and inactivation of genes that could dynamically affect the competition and survival of rhizobia in the rhizosphere.

Background: Centromere function is highly conserved across eukaryotes, but the underlying centromeric DNA sequences vary dramatically between species. Centromeres often contain a high proportion of repetitive DNA, such as tandem repeats and/or transposable elements (TEs). Einkorn wheat centromeres lack tandem repeat arrays and are instead composed mostly of the two long terminal repeat (LTR) retrotransposon families RLG_Cereba and RLG_Quinta which specifically insert in centromeres. However, it is poorly understood how these two TE families relate to each other and if and how they contribute to centromere function and evolution.

Results: Based on conservation of diagnostic motifs (LTRs, integrase and primer binding site and polypurine-tract), we propose that RLG_Cereba and RLG_Quinta are a pair of autonomous and non-autonomous partners, in which the autonomous RLG_Cereba contributes all the proteins required for transposition, while the non-autonomous RLG_Quinta contributes GAG protein. Phylogenetic analysis of predicted GAG proteins showed that the RLG_Cereba lineage was present for at least 100 million years in monocotyledon plants. In contrast, RLG_Quinta evolved from RLG_Cereba between 28 and 35 million years ago in the common ancestor of oat and wheat. Interestingly, the integrase of RLG_Cereba is fused to a so-called CR-domain, which is hypothesized to guide the integrase to the functional centromere. Indeed, ChIP-seq data and TE population analysis show only the youngest subfamilies of RLG_Cereba and RLG_Quinta are found in the active centromeres. Importantly, the LTRs of RLG_Quinta and RLG_Cereba are strongly associated with the presence of the centromere-specific CENH3 histone variant. We hypothesize that the LTRs of RLG_Cereba and RLG_Quinta contribute to wheat centromere integrity by phasing and/or placing CENH3 nucleosomes, thus favoring their persistence in the competitive centromere-niche.

Conclusion: Our data show that RLG_Cereba cross-mobilizes the non-autonomous RLG_Quinta retrotransposons. New copies of both families are specifically integrated into functional centromeres presumably through direct binding of the integrase CR domain to CENH3 histone variants. The LTRs of newly inserted RLG_Cereba and RLG_Quinta elements, in turn, recruit and/or phase new CENH3 deposition. This mutualistic interplay between the two TE families and the plant host dynamically maintains wheat centromeres.