The Coevolution of LINE-1 Retroelements and the Immune Restriction Factor TEX19

Abstract

This thesis explores coevolutionary dynamics between genomes and intragenomic parasites, focusing on LINE-1 retrotransposons in humans. LINE-1s persist and evolve despite robust defense mechanisms, suggesting an ongoing genetic conflict. The study investigates how human genomes combat LINE-1 activity through restriction factor genes. Our research tested 34 diverse human LINE-1s from an individual genome against various restriction factors, finding that while some genes, like APOBEC3B, consistently restrict LINE-1s, TEX19 shows variable restriction, with 11 LINE-1s showing strong evasion. These evasive LINE-1s are also active in vivo, evidenced by their replication and 3’ transductions in the human population. Additionally, variants of TEX19 in humans can lessen LINE-1 restriction, suggesting individual variability in LINE-1 regulation and potential implications for developmental disorders related to LINE-1s. The study further describes the dynamic evolution of TEX19 across mammals, identifying multiple independent duplications, losses, and structural variants, especially in rodents, bats, and carnivores. Ultimately, this work illustrates the intricate coevolution between LINE-1s and TEX19, highlighting the evolutionary arms race that shapes innate immune defenses and providing insights into the mechanisms of genomic stability and the evolutionary pressures shaping LINE-1 and restriction factor interactions in mammals.