Tighten Up or the Zombie Genes Will Get You
by Guest Blogger,
Tyler Kokjohn, Ph.D.
What happens when we die? This immensely interesting question has been answered in several different ways. The scientific study of death is challenging and results acquired from near death experience (NDE) subjects have produced controversy, not consensus. However, scientists have managed to figure out quite a few things about how our cells die and sometimes, refuse to die (1).
Our understanding of the death process is rudimentary and a recent study of dead animals yielded some unexpected results (2, 3). These scientists were working under a general assumption that the transcription of genes into RNA (gene expression) would cease quickly after death as physiologic failures mounted. Examining animals that were indisputably and irreversibly dead, their experiments revealed a wide range of brain and liver genes actually became more active during the post mortem period. Some genes just kept chugging along after death.
Absolutely fascinating, but what good is this knowledge? The investigators offered some speculations (3). If an afterlife for certain genes is found to be a general and reproducible phenomenon it might provide another means for forensic investigators to determine times of death. Death is a complex process in which organs and body parts perish at markedly different rates. This situation makes it possible to remove still-viable body parts from the dead and transplant them into others where they may continue to function for years. More work may reveal that gene expression profiles provide a better means to assess the state of preservation and health of donated organs before they are transplanted. Cadaveric transplants clearly provide tremendous benefits, but defining procedures for how and when potential donors may be declared dead poses significant medical and ethical challenges (4). The criteria employed influence what materials will be possible to transplant and the outcomes can sometimes be confusing; hearts harvested from donors declared deceased using cardiac death criteria have been transplanted successfully (4).
The mechanism causing some genes to become activated after death must still be determined, but the investigators have suggested a plausible model to investigate. They hypothesize that DNA chromosomes unwind in dead cells, allowing genes to become more accessible to the enzymes that transcribe them into RNA. At this stage it is unclear if and when the post mortem chromosome unraveling process begins or how genes activated after death might influence cell preservation. Perhaps donor organ preparation processes in the future will include measures to prevent activation of certain genes or inhibit their effects. However, this area is so new that transplant scientists could easily discover allowing some genes to be activated after death is beneficial.
Researchers investigating brain cancer made sense of some puzzling observations when they realized disruptions in chromosome structure ultimately activated genes promoting malignancy (5). Additional experiments using CRISPR gene editing methods support their idea specific changes in DNA folding patterns trigger cancer-promoting gene activity and suggest how to mitigate these pathologic alterations (6). Whether the same mechanisms underlie other cancers is under active investigation. It will be fascinating to see if death-induced genes are related to any diseases or the ageing process and how closely their activities correlate with DNA unwinding in living cells.
Perhaps it will become as routine for physicians of the future to assess the physical condition of your chromosomes as it is to take a peek at your tonsils today.
“That last gene expression profile suggests your chromosomes are starting to unwind. I am going to prescribe a topoisomerase activator to tighten them up. Otherwise a zombie gene might wake up and give you cancer.”
(1) L. Hayflick. 1994. How and Why We Age. Ballantine Books, New York.
(2) M. Leslie. 2016. ‘Undead’ Genes Come Alive Days after Life Ends. Science, 22 June 2016. http://www.sciencemag.org/news/2016/06/undead-genes-come-alive-days-after-life-ends
(3) A. E. Pozhitkov et al. 2016. Thanatotranscriptome: Genes Actively Expressed After Organismal Death. bioRχ, 11 June 2016. http://www.biorxiv.org/content/early/2016/06/11/058305
(4) R. D. Truog and F. G. Miller. 2008. The Dead Donor Rule and Organ Transplantation. The New England Journal of Medicine, 14 August 2008 (359:674-675). http://www.nejm.org/doi/full/10.1056/NEJMp0804474
(5) G. Kolata. 2015. Brain Cancers Reveal Novel Genetic Disruption in DNA. The New York Times, 23 December 2015. http://www.nytimes.com/2015/12/24/health/brain-cancers-reveal-novel-genetic-disruption-in-dna.html
(6) W. A. Flavahan et al. 2016. Insulator Dysfunction and Oncogene Activation in IDH Mutant Gliomas. Nature 529(7584):110-114. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831574/