A Population Genetics and Comparative Genomics perspective on the regulatory function of transposable elements in the human genome

Transposable elements (TEs) are DNA sequences that can change their location along the genome. Due to this particular feature, and to the fact that mammalian genomes are composed of TEs up to 30-50% of their length, TEs represent a potential powerful driver of genome evolution. Mounting evidence shows that the transposition process could be favorably exploited by the host in cases where it represents a selective advantage, in a phenomenon defined as TE exaptation. One such case is represented by the presence of functional sequences (ie. promoters, enhancers, insulators) embedded within the transposon sequence. The displacement of TEs bearing functional sequences could reshape the regulatory landscape of mammalian genomes, generating new regulatory interactions that might positively impact the host’s fitness. One way to assess the functional role of TEs is to investigate their associated selective regime: TEs with embedded functional sequences are expected to be subject to stronger selective pressure compared to TEs not overlapping functional sequences. In this work, we resort to population genetics and comparative genomics approaches that allow us to quantify the functional constraint acting on TEs across multiple evolutionary scales. Such an approach allows us to demonstrate that, despite a large number of TE classes behaving neutrally, many TE families manifest strong evidence of selection and, in some cases, conservation, permitting us to identify a set of TE classes putatively involved in host-beneficial biological processes.