EVOLUTION OF THE RETROTRANSPOSITION ACTIVITY OF LINE-1 IN THE HUMAN GENOME

Abstract

LINE-1 (Long Interspersed Nuclear Elements, L1) retrotransposons are the only autonomously active transposable elements in the human genome. Elevated retrotransposition activity of L1s are generally thought to be detrimental to the host. This study performed several analyses to investigate the evolution of the retrotransposition capacity among full-length human L1s. The first analysis showed that the rates at which new L1s emerge are positively correlated with retrotransposition activity values reported for cell-culture based assays, indicating that the retrotransposition activity values measured in cell culture can be considered as valid proxies for human germline retrotransposition capacity. An analysis that estimated the evolution of retrotransposition activity along the phylogenetic tree by sampling over various ancestral state configurations, revealed an evolutionary trend towards lower activity states. A penalized regression model was constructed to identify L1 sequence positions that might directly alter retrotransposition activity, yet the identified positions were not associated with any known biological L1 features. Analysis of sequence variation within L1 loci uncovered single nucleotide polymorphism (SNP) depletion within L1 transcription factor binding (TFB) sites, indicating evolutionary conservation of these sites by the host. Previous studies have shown that some of these TFB sites are essential for successful retrotransposition of human L1s. Together, these findings point towards the potentially ambivalent, yet balanced nature of the host-transposon relation.