From Fossils to Function: Transposable Elements in Regulatory Evolution

Transposable elements (TEs) have long been viewed as selfish genetic elements whose mobilization threatens genome integrity. However, increasing evidence from development, disease, and comparative genomics has revealed that TE-derived DNA, RNA, and proteins can be retained, repurposed, and repeatedly co-opted by host genomes. A central challenge is that TE function is highly context-dependent, where the same families that are silenced in most somatic cells can become active in early development, cancer, neural differentiation, immune activation, or experimentally sensitized chromatin states. Here, we review recent discoveries showing how TE-derived sequences contribute to gene regulation, three-dimensional genome organization, neurodevelopment, myelination, immunity, and disease-associated transcriptional programs. We emphasize that development and disease can expose shared regulatory capacities of TEs, and we discuss how long-read sequencing, TE-aware transcriptomics, chromatin profiling, and locus-specific perturbation are changing how the field interprets the TE record. In addition to asking whether TEs are selfish or beneficial, we argue that the field must ask when, where, and by what mechanism TE-derived sequences become functional.