Evolutionary insights from profiling LINE-1 activity at allelic resolution in a single human genome

Abstract

(Figure presented.) LINE-1 retrotransposons have dramatically shaped the human genome, however the count of active LINE-1s in each genome has remained unclear. This study functionally characterizes all the active LINE-1s from a single haplotype and reveals which LINE-1s have been recently active in humans. More highly active LINE-1s were identified than previously appreciated from analyses of reference genomes. Each individual carries a unique set of active LINE-1s due to polymorphic insertions and because of sequence variation in the allelic forms of highly prevalent LINE-1s in the population. Measurements of in vitro activity and inferences of in vivo fitness suggest specific amino acid changes that could represent adaptive changes essential for the persistence of LINE-1s in human genomes. In addition to the intensively studied presence/absence of LINE-1 insertions, mutations in LINE-1s that modulate their ability to replicate in vivo could contribute to the disease risk associated with the LINE-1s found in a person’s genome.