The dynamics of LINE-1 retrotransposition in cellular populations

Retrotransposons are genetic elements that have the ability to copy and paste themselves in the genome via the proteins they encode. Since the rapid growth of a retrotransposon can be highly deleterious at the organismal level, many of these genetic parasites are suppressed or have been inactivated over evolutionary time. However, the human genome still hosts the active retrotransposon LINE-1, whose aberrant expression is associated with disease, ranging from neurological disorders to cancer. Despite these associations, a quantitative understanding of the dynamics and diversity of LINE-1 insertions in somatic tissue is lacking. In order to address this gap, we present a population dynamic model of LINE-1 retrotransposition in individual cells. Using the model, we show that at demographic equilibrium, the LINE-1 copy number distribution is broader than would be expected from classical population genetic models. We demonstrate how this broadening distorts the frequency spectrum of insertions. We compare the model's predictions to data from whole genome sequencing of individual tumor cells.