Telomere-to-telomere co-mapping of transposable elements and human genes identifies a cluster of young L1 elements in...

Transposable elements (TEs) have played a central role in major evolutionary transitions across the human lineage, from eukaryogenesis to the emergence of the eutherian placenta, and are currently reactivated in cancer and autoimmune diseases. The complete telomere-to-telomere (T2T) assembly enables comprehensive investigation of TE contributions to gene regulation. Using a 10 kb window around transcription start sites, we mapped 3,709,429 human TEs to 28,738 genes against a 500-permutation background and assessed the enrichment and functional associations of 6 TE classes and 44 families. We identified a 220 kb interferon-alpha domain enriched with young L1 elements: 77 of its 175 TEs are evolutionary young L1 copies from 36 subfamilies, at mean divergence 135.7 against 188.2 genome-wide. This is consistent with recent L1 activity and could indicate a recent evolutionary arms-race affecting innate immune gene regulation. Distinct TE classes exhibited specific functional associations: SVA elements were enriched near genes involved in transcription termination; Alu elements were linked to RNA processing and splicing; MIR elements were associated with zinc homeostasis and voltage-gated potassium channel genes; LINE elements were enriched near genes related to lipid metabolism and olfactory perception; and LTR elements were associated with ion transport. This correlative map provides a positional baseline against which epigenomic and functional TE studies can be normalized, and a set of candidate loci for further investigation of evolutionary arms race.