Abstract
Mobile genetic elements play a major role in shaping biotic genomes and bringing about evolutionary transformations. Herein, a new class of mobile genetic elements is proposed in the form of circulating nucleic acids (CNAs) derived from the billions of cells that die in the body every day due to normal physiology and that act intra-corporeally. A recent study shows that CNAs can freely enter into healthy cells, integrate into their genomes by a unique mechanism and cause damage to their DNA. Being ubiquitous and continuously arising, CNA-induced DNA damage may be the underlying cause of ageing, ageing-related disabilities and the ultimate demise of the organism. Thus, DNA seems to act in the paradoxical roles of both preserver and destroyer of life. This new class of mobile genetic element may be relevant not only to multi-cellular organisms with established circulatory systems, but also to other multi-cellular organisms in which intra-corporeal mobility of nucleic acids may be mediated via the medium of extra-cellular fluid.
Highlights
Barbara McClintock published her classic paper on mobile genetic elements (MGEs) in 19501, but it took the scientific community several decades to appreciate the enormity of her discovery
Inter-genomic transposable elements, on the other hand, underlie horizontal or lateral gene transfer (HGT) whereby segments of DNA are transferred from one organism to another[7,8,9]
Circulating nucleic acids (CNAs) in the form of fragmented DNA and chromatin (DNAfs and Cfs) are known to circulate in blood and are derived from the hundreds of billions of cells that die through apoptosis in the adult human body on a daily basis[16,17]
Summary
Barbara McClintock published her classic paper on mobile genetic elements (MGEs) in 19501, but it took the scientific community several decades to appreciate the enormity of her discovery. Circulating nucleic acids (CNAs) in the form of fragmented DNA and chromatin (DNAfs and Cfs) are known to circulate in blood and are derived from the hundreds of billions of cells that die through apoptosis in the adult human body on a daily basis[16,17]. The intracellular DNAfs and Cfs trigger a DNA-damage-repair-response (DDR) with up-regulation of multiple pathways of DNA damage and repair that facilitate their integration into host cell genome. The activated DDR joins up multiple disparate DNAfs and Cfs into long concatemers by non-homologous-end-joining as a part of the repair process It is the integration into the host cell genomes of the concatemers by homologous or non-homologous recombination that brings about damage to DNA. These include auto-immune disorders[27], and a host of acute and chronic human pathologies, namely, sepsis[28], trauma[29], burns[30], organ transplantation[31], diabetes[32], myocardial infarction[33], stroke[34] and renal failure[35]
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