Biology subjects

Goubert, C.

Publications and source records attributed to Goubert, C..

14 recordsLinked to original sources

bioRxiv2026

Updated Transposable Element Libraries for Drosophila melanogaster in Dfam 4.0

Drosophila melanogaster repeatome, comprising roughly 20% of the genome, is characterized by a large fraction of active TE families counterbalanced by efficient purifying selection. Consequently, many TE families persist at low copy numbers and are frequently population specific. Hybridization and horizontal transfer provide new families, which can spread through natural populations within decades. These dynamics, together with years of independent curation efforts, left the D. melanogaster mobilome distributed across several, partly redundant, libraries. Prompted by submissions of population-specific data, we undertook a complete overhaul of the D. melanogaster TE libraries, begun in Dfam 3.9 and finalized in Dfam 4.0. We cross-referenced the new submissions against Repbase, FlyBase, the Berkeley Drosophila Genome Project, and our own Dfam 3.8 to resolve redundancy and reconcile names, then rebuilt or newly constructed the seed alignment for most families. Seeds came from four sources: the dm6 reference itself, which supported the majority of models; insertions >100 bp from 13 samples of a recently published D. melanogaster pangenome; the genomes of other members of the D. melanogaster subgroup, which supplied copies for older families too degraded in dm6 alone; and diverged matches recovered during iterative curation, which resolved into subfamilies and previously undescribed relatives. Rebuilding the seeds corrected consensus sequences that were truncated, chimeric, or skewed by co-duplicated fragments, and lowered the mean Kimura divergence of annotated copies from their consensus. The revision also added families with no prior Dfam representation, including the DNA P-element (absent from dm6) and a collection of novel families that have recently invaded natural populations. Following manual curation, the new library contains 398 models, up from 226 in Dfam 3.8, and annotates an additional 1.5% of the dm6 reference.

genomics↗

bioRxiv2026

Long-read sequencing maps transposable element variation and its regulatory and epigenetic effects in the human brain

Transposable elements (TEs) are mobile DNA sequences that shape genome architecture and gene regulation, yet their roles in the human brain remain largely unresolved. Short-read sequencing lacks the resolution to accurately map TE insertions, detect associated structural variants, and resolve highly repetitive regions. Here, we leverage long-read whole-genome sequencing to profile germline TE insertions in postmortem brain tissue from two ancestrally diverse cohorts: the North American Brain Expression Consortium (NABEC; European ancestry, n = 205) and the Human Brain Collection Core (HBCC; African and African-admixed ancestry, n = 146). We identified 2,842 and 1,660 high-confidence non-reference insertions in HBCC and NABEC, respectively, spanning Alu, LINE-1, and SVA elements. We then also further characterized complex short tandem repeat and variable number tandem repeat variation within reference SVA and Alu loci. Reference TEs were also found to mediate complex structural variants at loci implicated in brain development and neurodegenerative disease, with several showing ancestry-specific patterns. Integration of bulk RNA-sequencing data identified TE expression quantitative trait loci, including insertions that modulate neuronal gene expression. Single-nucleus RNA sequencing revealed cell-type-specific effects of TE regulation across cortical populations. Long-read methylation profiling further demonstrated age-associated epigenetic regulation of both reference and non-reference Alu elements. As a community resource, we release a catalog of TE insertions, allele frequencies, and ancestry-specific distributions to enable future functional and disease-focused investigations. Together, these findings highlight the widespread regulatory and epigenetic influence of TEs in the human brain and establish long-read sequencing as a powerful approach for uncovering cell-type- and population-specific TE dynamics.

genomics↗

bioRxiv2025

Chromosomal inversions mediated by tandem insertions of transposable elements

Chromosomal inversions play a crucial role in evolution by influencing phenotypes through the linkage of co-adapted alleles. While inversions have been found across a large number of taxa, mapping and characterizing inversion breakpoint regions remains challenging, often due to the presence of complex tandem repeats and transposable elements (TEs). Here, we identify and quantify TEs in the breakpoints of the four large-scale inversions previously reported in Atlantic cod, leveraging on three high-quality long-read-based reference genome assemblies for the Norwegian Coastal cod, the Northeast Arctic cod and Celtic cod ecotypes. We detected a significant enrichment of TE orders and superfamilies with terminal inverted repeats (TIRs) within the inversion breakpoints of chromosomes 1, 7 and 12. Notably, we discovered a tandem accumulation of miniature inverted-repeat transposable elements (MITEs) belonging to a family of hAT transposons, exclusively residing in the breakpoints of the inverted haplotype on chromosomes 1 and 7 found in the Northeast Arctic cod. The accumulation of tandemly arranged TEs in breakpoint regions suggests that they have driven the appearance of inversions through ectopic recombination, further supporting the potential of TEs in facilitating chromosomal reorganizations with large evolutionary implications.

evolutionary biology↗

bioRxiv2024

Genomic stability in the Galapagos Scalesia adaptive radiation: Consistent transposable element accumulation despite hybridization and ecological niche shifts

Transposable elements (TEs) have been hypothesized to play a pivotal role in driving diversification by facilitating the emergence of novel phenotypes and the accumulation of divergence between species. Hybridization and adaptation to novel niches are hypothesized to influence TE accumulation in genomes by disrupting genomic regulation, including the suppression of TE replication. The rapid speciation and ecological diversification characteristic of adaptive radiations offer a unique opportunity to examine the link between TE accumulation and speciation, diversification, hybridization and adaptation. Here, focusing on all 15 species of the genus Scalesia (Asteraceae), a radiation endemic to the Galapagos Islands, we test whether hybridization or shifts in ecological niche are associated with changes in TE accumulation in genomes. Our analyses reveal little to no variation in TE accumulation among Scalesia species nor its hybrid populations. Shifts in ecological niches, linked to climatic variation, did not result in discernible changes in TE accumulation, a surprising finding given the anticipated selective pressure imposed by aridity, a factor often linked to genome size reduction. We found no distinct patterns in the temporal accumulation of TEs, and no effects at the class or superfamily level. Our findings challenge the assertion that TEs have directly driven diversification, speciation and local adaptation. Instead, we suggest that TEs may simply be along for the ride, rather than actively contributing to plant diversification.

evolutionary biology↗

bioRxiv2024

Consistent accumulation of transposable elements in species of the Hawaiian Tetragnatha spiny-leg adaptive radiation across the archipelago chronosequence

The ecological and phenotypic diversity observed in oceanic island radiations presents an evolutionary paradox: a high level of genetic variation is typically required for diversification, but species colonizing a new island typically suffer from founder effects. This reduction in population size leads to a reduction in genetic diversity, which ultimately results in a reduction in the efficiency of natural selection. Then, what is the source of genetic variation which acts as the raw material for ecological and phenotypic diversification in oceanic archipelagos? Transposable elements (TEs) are mobile genetic elements that have been linked to the generation of genetic diversity, and evidence suggests that TE activity and accumulation along the genome can result from reductions in population size. Here, we use the Hawaiian spiny-leg spider radiation (Tetragnatha) to test whether TE accumulation increases due to demographic processes associated with island colonization. We sequenced and quantified TEs in 23 individuals from the spiny-leg radiation and 4 individuals from its sister radiation, the Hawaiian web-building Tetragnatha. Our results show that founder effects resulting from colonization of new islands have not resulted in TE accumulation over evolutionary time. Specifically, we found no evidence for increase in abundance of specific TE superfamilies, nor an accumulation of young TEs in lineages which have recently colonized a new island or are present in islands with active volcanoes. We also found that the DNA/hAT transposon superfamily is by far the most abundant TE superfamily in the Tetragnatha radiation. This work shows that TE abundance has remained constant for the spiny-leg radiation across the archipelago chronosequence, and TE accumulation is not affected by population oscillations associated with island colonization events. Therefore, despite their known role in the generation of genetic diversity, TE activity does not appear to be the mechanism to explain the evolutionary paradox of the insular Tetragnatha spiny-leg radiation.

evolutionary biology↗

bioRxiv2023

Cryptic endogenous retrovirus subfamilies in the primate lineage

Many endogenous retroviruses (ERVs) in the human genome are primate-specific and have contributed novel cis-regulatory elements and transcripts. However, current approaches for classifying and annotating ERVs and their long terminal repeats (LTRs) have limited resolution and are inaccurate. Here, we developed a new annotation based on phylogenetic analysis and cross-species conservation. Focusing on the evolutionary young MER11A/B/C subfamilies, we revealed the presence of 4 new subfamilies, that better explained the epigenetic heterogeneity observed within the MER11 instances, suggesting a new annotation for 412 (19.8%) of these repeat elements. Furthermore, we functionally validated the regulatory potential of these four new subfamilies using a massively parallel reporter assay (MPRA), which also identified motifs associated with their differential activities. Combining MPRA with new annotations across primates revealed an apes-specific gain of SOX related motifs through a single-nucleotide deletion. Lastly, by applying our approach across 53 simian-enriched LTR subfamilies, we defined a total of 75 new subfamilies and found that 3,807 (30.0%) instances from 26 LTR subfamilies could be categorized into a novel annotation, many of which with a distinct epigenetic profile. Thus, with our refined annotation of simian-enriched LTRs, it will be possible to better understand the evolution in primate genomes and potentially identify new roles for ERVs and their LTRs in the hosts.

genomics↗

bioRxiv2023

GraffiTE: a Unified Framework to Analyze Transposable Element Insertion Polymorphisms using Genome-graphs

Transposable Elements are ubiquitous mobile DNA sequences evolving among their hosts genomes, generating insertion polymorphisms that contribute to genomic diversity. We present GraffiTE, a flexible pipeline to analyze polymorphic mobile elements. By integrating state-of-the-art structural variant detection algorithms and graph genomes, GraffiTE identifies polymorphic mobile elements from genomic assemblies and/or long-read sequencing data, and genotypes these variants using short or long read sets. Benchmarking on simulated and real datasets reports high precision and recall rates. GraffiTE is designed to allow non-expert users to perform comprehensive analyses, including in models with limited transposable element knowledge and is compatible with various sequencing technologies. GraffiTE is freely available at https://github.com/cgroza/GraffiTE. Here, we demonstrate the versatility of GraffiTE by analyzing human, Drosophila melanogaster, maize, and Cannabis sativa pangenome data. These analyses reveal the landscapes of polymorphic mobile elements and their frequency variations across individuals, strains, and cultivars.

bioinformatics↗

bioRxiv2023

Detection and identification of transposable element transcripts using Long Read RNA-seq in Drosophila germline tissues

Transposable elements (TEs) are repeated DNA sequences potentially able to move throughout the genome. In addition to their inherent mutagenic effects, TEs can disrupt nearby genes by donating their intrinsic regulatory sequences, for instance, promoting the ectopic expression of a cellular gene. TE transcription is therefore not only necessary for TE transposition per se but can also be associated with TE-gene fusion transcripts, and in some cases, be the product of pervasive transcription. Hence, correctly determining the transcription state of a TE copy is essential to apprehend the impact of the TE in the host genome. Methods to identify and quantify TE transcription have mostly relied on short RNA-seq reads to estimate TE expression at the family level while using specific algorithms to discriminate copy-specific transcription. However, assigning short reads to their correct genomic location, and genomic feature is not trivial. Here we retrieved full-length cDNA (TeloPrime, Lexogen) of Drosophila melanogaster gonads and sequenced them using Oxford Nanopore Technologies. We show that long-read RNA-seq can be used to identify and quantify transcribed TEs at the copy level. In particular, TE insertions overlapping annotated genes are better estimated using long reads than short reads. Nevertheless, long TE transcripts (> 4.5 kb) are not well captured. Most expressed TE insertions correspond to copies that have lost their ability to transpose, and within a family, only a few copies are indeed expressed. Long-read sequencing also allowed the identification of spliced transcripts for around 107 TE copies. Overall, this first comparison of TEs between testes and ovaries uncovers differences in their transcriptional landscape, at the subclass and insertion level.

bioinformatics↗

bioRxiv2022

Genomic features underlie the co-option of SVA transposons as cis-regulatory elements in human pluripotent stem cells

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where [~]3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication into human stem-cell gene regulation. We found that [~]750 SVAs are co-opted as functional cis-regulatory elements in human induced pluripotent stem cells. These SVAs are significantly closer to genes and harbor more transcription factor binding sites than non-co-opted SVAs. We show that a long DNA motif composed of flanking YY1/2 and OCT4 binding sites is enriched in the co-opted SVAs and that these two transcription factors bind consecutively on the TE sequence. We used CRISPRi to epigenetically repress active SVAs in stem cell-like NCCIT cells. Epigenetic perturbation of active SVAs strongly attenuated YY1/OCT4 binding and influenced neighboring gene expression. Ultimately, SVA repression resulted in [~]3,000 differentially expressed genes, 131 of which were the nearest gene to an annotated SVA. In summary, we demonstrated that SVAs modulate human gene expression, and uncovered that location and sequence composition contribute to SVA domestication into gene regulatory networks.

genomics↗

bioRxiv2021

The genome sequence of the cereal pest Sitophilus oryzae: an unprecedented transposable element content

BackgroundThe rice weevil Sitophilus oryzae is one of the most important agricultural pests, causing extensive damage to cereal in fields and to stored grains. S. oryzae has an intracellular symbiotic relationship (endosymbiosis) with the Gram-negative bacterium Sodalis pierantonius and is a valuable model to decipher host-symbiont molecular interactions. ResultsWe sequenced the Sitophilus oryzae genome using a combination of short and long reads to produce the best assembly for a Curculionidae species to date. We show that S. oryzae has undergone successive bursts of transposable element (TE) amplification, representing 72% of the genome. In addition, we show that many TE families are transcriptionally active, and changes in their expression are associated with insect endosymbiotic state. S. oryzae has undergone a high gene expansion rate, when compared to other beetles. Reconstruction of host-symbiont metabolic networks revealed that, despite its recent association with cereal weevils (30 Kyear), S. pierantonius relies on the host for several amino acids and nucleotides to survive and to produce vitamins and essential amino-acids required for insect development and cuticle biosynthesis. ConclusionsHere we present the genome of an agricultural pest beetle, which may act as a foundation for pest control. In addition, S. oryzae may be a useful model for endosymbiosis, and studying TE evolution and regulation, along with the impact of TEs on eukaryotic genomes.

genomics↗

bioRxiv2019

RepeatModeler2: automated genomic discovery of transposable element families

The accelerating pace of genome sequencing throughout the tree of life is driving the need for improved unsupervised annotation of genome components such as transposable elements (TEs). Because the types and sequences of TEs are highly variable across species, automated TE discovery and annotation are challenging and time-consuming tasks. A critical first step is the de novo identification and accurate compilation of sequence models representing all the unique TE families dispersed in the genome. Here we introduce RepeatModeler2, a new pipeline that greatly facilitates this process. This new program brings substantial improvements over the original version of RepeatModeler, one of the most widely used tools for TE discovery. In particular, this version incorporates a module for structural discovery of complete LTR retroelements, which are widespread in eukaryotic genomes but recalcitrant to automated identification because of their size and sequence complexity. We benchmarked RepeatModeler2 on three model species with diverse TE landscapes and high-quality, manually curated TE libraries: Drosophila melanogaster (fruit fly), Danio rerio (zebrafish), and Oryza sativa (rice). In these three species, RepeatModeler2 identified approximately three times more consensus sequences matching with >95% sequence identity and sequence coverage to the manually curated sequences than the original RepeatModeler. As expected, the greatest improvement is for LTR retroelements. The program had an extremely low false positive rate when applied to simulated genomes devoid of TEs. Thus, RepeatModeler2 represents a valuable addition to the genome annotation toolkit that will enhance the identification and study of TEs in eukaryotic genome sequences. RepeatModeler2 is available as source code or a containerized package under an open license (https://github.com/Dfam-consortium/RepeatModeler, https://github.com/Dfam-consortium/TETools). SignificanceGenome sequences are being produced for more and more eukaryotic species. The bulk of these genomes is composed of parasitic, self-mobilizing transposable elements (TEs) that play important roles in organismal evolution. Thus there is a pressing need for developing software that can accurately identify the diverse set of TEs dispersed in genome sequences. Here we introduce RepeatModeler2, an easy-to-use package for the curation of reference TE libraries which can be applied to any eukaryotic species. Through several major improvements over the previous version, RepeatModeler2 is able to produce libraries that recapitulate the known composition of three model species with some of the most complex TE landscapes. Thus RepeatModeler2 will greatly enhance the discovery and annotation of TEs in genome sequences.

genomics↗

bioRxiv2019

TypeTE: a tool to genotype mobile element insertions from whole genome resequencing data

Alu retrotransposons account for more than 10% of the human genome, and insertions of these elements create structural variants segregating in human populations. Such polymorphic Alu are powerful markers to understand population structure, and they represent variants that can greatly impact genome function, including gene expression. Accurate genotyping of Alu and other mobile elements has been challenging. Indeed, we found that Alu genotypes previously called for the 1000 Genomes Project are sometimes erroneous, which poses significant problems for phasing these insertions with other variants that comprise the haplotype. To ameliorate this issue, we introduce a new pipeline -- TypeTE -- which genotypes Alu insertions from whole-genome sequencing data. Starting from a list of polymorphic Alus, TypeTE identifies the hallmarks (poly-A tail and target site duplication) and orientation of Alu insertions using local re-assembly to reconstruct presence and absence alleles. Genotype likelihoods are then computed after re-mapping sequencing reads to the reconstructed alleles. Using a gold standard set of PCR-based genotyping of >200 loci, we show that TypeTE improves genotype accuracy from 83% to 92% in the 1000 Genomes dataset. TypeTE can be readily adapted to other retrotransposon families and brings a valuable toolbox addition for population genomics.

bioinformatics↗

bioRxiv2019

Contribution of unfixed transposable element insertions to human regulatory variation

Thousands of unfixed transposable element (TE) insertions segregate in the human population, but little is known about their impact on genome function. Recently, a few studies associated polymorphic TE insertions to mRNA levels of adjacent genes, but the biological significance of these associations, their replicability across cell types, and the mechanisms by which they may regulate genes remain largely unknown. Here we performed a TE-expression QTL analysis of 444 lymphoblastoid cell lines and 294 induced pluripotent stem cells using a newly developed set of genotypes for 2,806 polymorphic TE insertions. We identified 211 and 324 TE-eQTL acting in cis in each respective cell type. Approximately one fourth were shared across cell types with strongly correlated effects. Furthermore, analysis of chromatin accessibility QTL in a subset of the lymphoblastoid cell lines suggests that unfixed TEs often modulate the activity of enhancers and other distal regulatory DNA elements, which tend to lose accessibility when a TE inserts within them. We also document a case of an unfixed TE likely influencing gene expression at the post-transcriptional level. Our study points to broad and diverse cis-regulatory effects of unfixed TEs in the human population and underscores their plausible contribution to phenotypic variation.

genomics↗

bioRxiv2018

Genomic analysis of European Drosophila melanogaster populations on a dense spatial scale reveals longitudinal population structure and continent-wide selection

Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatio-temporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in European Drosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterise variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.

evolutionary biology↗