Evolutionary arms race between transposable elements and human genes: telomere-to-telomere genome comprehensive analysis identifies young L1 clusters in the interferon-alpha domain

This is a Preprint and has not been peer reviewed. This is version 2 of this Preprint. You must log in to post a comment. There are no comments or no comments have been made public for this article. This is a Preprint and has not been peer reviewed. This is version 2 of this Preprint. Add a Comment You must log in to post a comment. Comments There are no comments or no comments have been made public for this article. - Supplementary Figure 1 - Supplementary Figure 2 - Supplementary Figure 3 - Supplementary Figure 4 - Supplementary Figure 5 - Supplementary Figure 6 - Supplementary Figure 7 - Supplementary Figure 8 - Supplementary File 1 - Supplementary File 2 - Supplementary File 3 - Supplementary File 4 - Supplementary File 5 - Supplementary File6 - Supplementary File 7 - Supplementary File 8 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 availability of the complete telomere-to-telomere (T2T) human genome assembly enables comprehensive investigation of TE contributions to gene regulation. Using a 10 kb window in the T2T genome, we performed comprehensive mapping of 3,709,429 human TEs to 28,738 genes with random background correction and assessed the enrichment and functional associations of six TE classes and 44 families. We identified a 220 kb interferon-alpha genomic domain enriched with evolutionarily young L1 elements, suggesting a recent evolutionary arms race influencing innate immune responses. 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 genes involved in zinc, copper, and cadmium detoxification; LINE elements were enriched near genes related to lipid metabolism and olfactory perception; and LTR elements were potentially associated with potassium ion channel function. This proximity-based analysis provides a foundational framework for evaluating the functional impact of transposable elements on human gene regulation and their role in driving regulatory innovation. https://doi.org/10.32942/X2FM2M Life Sciences transposable elements, evolutionary arms-race, T2T genome, interferon alpha, functional enrichment Published: 2026-04-18 01:13 Last Updated: 2026-05-03 04:59 CC BY Attribution 4.0 International Data and Code Availability Statement: All code used for the comprehensive proximity mapping, statistical analysis, and GO functional networking is available in the GitHub repository: https://github.com/Nikit357/T2T_genes_evolution. Tables of TE-gene intersections, including divergence and family-level enrichment statistics, have been deposited in the same GitHub repository. Language: English