Apoptosis uncovers human evolutionary heritage sequestered in non-coding DNA

Abstract

Cell-free chromatin particles (cfChPs), primarily derived from non-coding DNA (ncDNA) and released from apoptotic cells into the bloodstream, can be horizontally transferred into living cells. However, their potential role in generating ncDNA within recipient cells remains unknown. We previously reported that cfChP- sized fragments generated upon sonicating high-molecular-weight DNA can indiscriminately transmit themselves into foreign cells across species and kingdom boundaries. We hypothesized that cfChP-like DNA-protein complexes generated following organismal death have been exchanged among species and have progressively accumulated to form a dense patchwork that now constitutes the ncDNA, and that apoptosis may dissociate these complexes, rendering them amenable to detection. To test this hypothesis, we used species-specific DNA fluorescent in situ hybridisation probes and antibodies against archaea, eubacteria, plants, algae, fungi, protozoa, Drosophila, fish, chicken, mouse, rat, pig, dog, and monkey on intact and apoptotic human cells. We detected no reactivity with intact cells but strong reactivity with the ncDNA component of apoptotic cells. These findings indicate that ncDNA represents a dense conglomeration of DNA-protein complexes derived from different species that become detectable following apoptosis. This suggests that human evolutionary heritage is conserved within ncDNA formed through progressive accumulation of genetic fragments transferred horizontally following organismal death.