Expression spectrum of TE-derived transcripts in human adult tissues

Miao, B.; Zhang, B.; WU, T. P.; Luo, X.; Ademovic, A.; Yang, Y.

doi:10.1101/2025.03.29.646092

Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.03.29.646092

Expression spectrum of TE-derived transcripts in human adult tissues

Miao, B.·Zhang, B.·WU, T. P.·Luo, X.·Ademovic, A.·Yang, Y.

View original source ↗Export metadata ↓

Abstract

Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored. In this study, we systematically analyzed 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-derived transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific gene regulation. We identified sex-specific expression of TE-derived transcripts regulated by sex hormones in breast tissue between females and males. Our results demonstrated that TE-derived alternative transcription initiation significantly enhances the variety of translated protein products, e.g., changes in the N-terminal peptide length of WNT2B caused by TE-derived transcription result in isoform-specific subcellular localization. Additionally, we identified 68 human-specific TE-derived transcripts associated with metabolic processes and environmental adaptation. Together, these findings highlight the pivotal evolutionary role of TEs in shaping the human transcriptome, demonstrating how conserved and human-specific TEs contribute to transcriptional and translational innovation in human genome evolution.

Explore related subjects

genomics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Miao, B., Zhang, B., WU, T. P., Luo, X., Ademovic, A., Yang, Y.. 2025-04-03. Expression spectrum of TE-derived transcripts in human adult tissues. https://doi.org/10.1101/2025.03.29.646092

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Time-resolved single-cell screening reveals the dynamic regulatory architecture of human cardiogenesis

Congenital heart disease (CHD) originates during early embryogenesis, yet when disease genes act cannot be determined from existing data. Human fetal heart atlases lack critical time points, and perturbation screens that systematically assess gene function currently profile at most a few time points. Here we combined single-cell CRISPR screening of 400 disease-relevant genes in cardioids, sampled daily over seven developmental days (~975,000 cells), with a matched multiome atlas. Perturbation phenotypes were strongly dependent on developmental stage. Perturbations that reshaped cell-fate allocation or gene expression were enriched for CHD-linked genes, and most acted already during progenitor stages. Timing was largely independent of the target gene's own expression, marking instead when a cell state became functionally dependent on it, and some effects persisted after expression declined. Consensus gene regulatory networks integrating perturbation and multiome data recovered stage-specific regulators and nominated HOXB2 and HOXB3 as candidate cardiac regulators. Many perturbations converged on shared downstream programmes, which were reorganised through differentiation. Effects correlated in progenitors were maintained in differentiated cells, split into distinct programmes, converged with other perturbations or disappeared entirely, indicating that gene function is highly context dependent. Beyond advancing our understanding of the developmental regulatory logic underlying CHD, our work provides a resource for developing context-dependent models for in silico prediction of perturbation effects.

genomics↗

bioRxiv2026

A Y-specific translocated gsdf copy is a candidate master sex-determining gene in common dab (Limanda limanda)

Sex-determining systems in flatfishes are highly diverse, and even closely related species can differ in both sex-determining loci and heterogametic systems. In common dab (Limanda limanda), the genetic basis of sex determination has not yet been established. Here, we investigated sex determination using pooled whole-genome sequencing combined with long-read genome sequencing of females and males from Iceland and Norway. Genome-wide allele-frequency analyses identified sex-associated regions consistent with male heterogamety (XX/XY), with the strongest signal on chromosome 16. Comparison of the existing reference assembly, which represents an X haplotype at this locus, with a haplotype-resolved male PacBio HiFi assembly revealed a [~]21.5 kb Y-specific insertion on chromosome 16. The insertion showed complete coverage in male pools but little or no coverage in female pools from either population. It contained a translocated genomic segment including a copy of gonadal soma-derived factor (gsdf) and a predicted gene of unknown function. Comparative genomic analyses were consistent with this segment originating from an autosomal gsdf-containing region on chromosome 1. Given the recurrent recruitment of gsdf as a sex-determining factor in teleosts, we designate the Y-linked copy gsdfY and identify it as the strongest candidate for the master sex-determining gene in common dab. Additional broad sex-associated differentiation on chromosome 19 was restricted to the Icelandic samples and may reflect population-specific expansion of the sex-linked region, although its structural basis remains unresolved. Together, these findings provide the first genomic characterization of sex determination in common dab and demonstrate how gene duplication and translocation can contribute to the evolution of novel sex-determining systems in flatfishes.

genomics↗

bioRxiv2026

A population-scale isoform atlas enables isoform-based trait association and regulatory analysis in lettuce

Genomic variation shapes phenotypic diversity, yet how genetic variation contributes to transcript isoform diversity remains poorly understood at the population scale. Here, we integrated transcriptomic data from 240 lettuce accessions with a lettuce pangenome to construct a comprehensive pan isoform atlas comprising 531,657 isoforms from 49,729 transcribed loci. Isoform presence absence variation (iPAV) captured extensive transcript diversification during domestication and horticultural differentiation, providing additional resolution beyond locus-level analyses, particularly within loci shared across the population. To facilitate the systematic analysis of isoform trait associations, we developed ISONET-GWAS, a computational framework that integrates isoform-based association mapping, functional annotation, and network-based candidate prioritization. ISONET-GWAS recovered the known chlorophyll regulator LsGLK, identified 455 metabolite isoform associations across 77 metabolites, and prioritized candidate regulators of chlorophyll metabolism supported by functional validation. Genome-wide splicing quantitative trait locus (sQTL) mapping identified 10,498 sQTL associations, revealing widespread distal genetic associations with alternative splicing and candidate trans-sQTL hotspots. Notably, we identified a trans-sQTL hotspot overlapping LsPPR, which encodes a pentatricopeptide repeat RNA-binding protein. Perturbation of LsPPR resulted in widespread changes in alternative splicing of floweing-related genes, accompanied by delayed bolting and flowering and altered splicing of flowering-related genes. Together, our study establishes a population-scale pan-isoform resource and a broadly applicable analytical strategy for isoform-level trait association, candidate prioritization, and complementary analysis of the genetic regulation of alternative splicing in crops.

genomics↗