Horizontally transferred cell-free chromatin particles function as miniature “predatory” genomes and vehicles for transposable elements within host cells

Abstract

AbstractWe previously reported that cell-free chromatin particles (cfChPs) - chromosomal fragments released from the billions of dying cells - that circulate in human blood are horizontally transferred to healthy cells with biological effects. However, the underlying mechanism and function of these effects remained unclear. We treated NIH3T3 mouse fibroblasts cells with cfChPs isolated from human serum and using chromatin fibre fluorography, cytogenetic analysis, immuno-fluorescence and fluorescentin situhybridisation investigated the intracellular activities of cfChPs. We found that the internalised cfChPs containing disparate DNA sequences had randomly combined to form complex concatemers some of which were ostensibly multi-mega base pairs in size. The concatemers performed many functions attributable to the nuclear genome. They could replicate and synthesize numerous proteins which appeared as highly complex fusion proteins. The concatemers harboured human LINE-1 andAluelements and increased their copy number with time in culture. These findings lead us to hypothesise that a cell simultaneously harbours two genome forms that function autonomously: one that is inherited (hereditary genome) and numerous others that are acquired (miniature predatory genomes). The presence of miniature predatory genomes has evolutionary implications given their ability to generate a plethora of novel proteins and to serve as vehicles for transposable elements.