Florian Guilllou

PGBD5 is encoded by a gene domesticated at the chordate origin from a DNA transposon of the piggyBac family. During its evolution, PGBD5’s sequence has been under strong purifying selection among vertebrate genomes. This suggests PGBD5 functions in the development and physiology of chordates, as recently demonstrated in mouse and human brain development, where it was implicated in double strand DNA breaks on neurons. However, biochemical PGBD5 activities remain undefined due to lack of appropriate in vitro model systems. Furthermore, coevolution of PGBD5 with hosts has likely reshaped some of its functions, resulting in differences between vertebrate PGBD5 and the insect piggybac transposase (PB). Recent studies have found that PGBD5 can interact with two different “species” of piggyBac -like transposon element ( pble ). Here, we show that human PGBD5 can interact with four “species” human pbles and to promote their chromosomal integration in cells, a property it shares with insect PB. Human PGBD5 can also bind to distinct chromosomal copies of human pble in cell type-specific manner, and to genomic loci containing inverted repeats in human cells akin to those found in subterminal insect pble ends. These findings expand the scope of potential biological activities of PGBD5 and other domesticated DNA transposases.