Retrotransposons in human evolution and brain diseases: investigating modern and ancient variability through the lens of mobile elements

Transposable Elements (TEs) are mobile genetic elements with the ability to replicate themselves and insert their copies in a new genomic location; notably, sequences derived from TEs make up to 53-60% of the human genome. While the vast majority of TEs are not transpositionally active, they can still play functional roles such as modulating the expression or alternative splicing of nearby genes. Moreover, they can generate potentially inheritable insertions, thereby creating human-specific polymorphisms, that in the last years have been used to study human evolution, variability and susceptibility to medical disorders. Here we present a large-scale in silico study on polymorphic TEs, used as genetic variability markers in modern human populations and ancient genomes. Furthermore, we investigated the possible role of TEs in conferring a risk of developing brain disorders, such as addiction, schizophrenia and Alzheimer’s disease. Our results point toward an important role of polymorphic TEs in: 1) shaping human genome evolution, especially the neural genome and human-specific cognitive abilities; 2) influencing phenotypic variability and adaptation; 3) being the target of recent instances of positive selection or more ancient event of adaptive introgression; 4) conferring risk of developing neuro-psychiatric disorders.