Preprint: pangenome study resolves polymorphic transposable elements as active drivers of human regulatory evolution

A preprint on bioRxiv describes a systematic analysis of polymorphic transposable elements (TEs) — those still segregating in human populations rather than fixed in the genome — using 231 haplotype-resolved human pangenomes paired with long-read epigenomic and transcriptomic data.

Most existing knowledge of TE contributions to gene regulation derives from ancient insertions already fixed across all humans: elements whose regulatory consequences have been observed and filtered by evolution over millions of years. The polymorphic phase — where a TE insertion is present in some individuals but absent in others — has been difficult to study because short-read sequencing cannot reliably resolve TE alleles as sequences. Long-read pangenomics changes this, enabling the authors to characterise segregating TE alleles not just as presence/absence markers but as full sequences with associated epigenetic states and splicing consequences.

The study finds that polymorphic TEs are active contributors to regulatory variation in living human populations: they influence chromatin accessibility, DNA methylation, and gene expression in ways that overlap with functional GWAS signals. Their origins extend beyond recent transposition events, and their regulatory activity is shaped by the genomic and epigenomic context into which they insert. The preprint has not been peer-reviewed. Population geneticists, functional genomicists, and researchers working on non-coding variation and regulatory evolution will find this a methodologically and conceptually significant contribution.