The Thanatotranscriptome – Life after death?

Matt Ambrose

Is death as final as we have always assumed? Or do our cells take up another task once we, the drivers of the machines we call our bodies, are gone? A team led by Peter A. Noble of the University of Washington pre-published a paper in June of last year (now published in the peer-reviewed open-access journal Royal Society Open Biology) which shed some light on the final gasp of life in our cells.

When we refer to death in everyday terms, what we are describing is what is known in cell biology as ‘organismal death’ – overall death of the body i.e. when the final sparks of activity in our incredible brains fade away, and the heart stops pumping. But what happens to individual cells in the body when this happens?

Despite the cut-off of oxygen and energy to our cells, it is now understood that some cells can function, to a degree, up to 96 hours after organismal death, still decoding genes and transcribing them into RNA, as they are doing right now everywhere in your body for a myriad of reasons. This discovery is at the heart of the paper published by Noble and his colleagues.

So what is the Thanatotranscriptome? Deriving from the words Thanatos, the Ancient Greek personification of death, and transcriptome, the general term in biology for the genes in an organism’s DNA that are decoded and transcribed to make proteins, the Thanatotranscriptome is an umbrella term covering all the genes that are transcribed after organismal death.

Let’s quickly recap how genes work. A gene is simply a section of an organism’s DNA that, in its unique sequence of the four nucleotide bases, codes for a section of protein. This protein will then go on to either wholly or partially (along with other proteins from other genes) determine a certain characteristic such as eye colour, how fast your hair grows, or how susceptible you are to some diseases; practically any characteristic you can think of.

So what did the study find? The main thing the researchers were looking for was what is called ‘upregulation’; when activity (specifically transcription, the decoding of genes in order to allow the production of proteins) associated with a particular gene increases. They examined transcription levels in the whole bodies of zebrafish, Danio rerio, and in the brains and livers of house mice, Mus musculus, at a number of different times after sudden death of the organism.

Their results were expected in some areas and surprising in others. The researchers found that there were increases in transcription of genes associated with a number of factors, including stress, immunity, inflammation, and apoptosis (genetically programmed individual cell death; if a cell becomes cancerous, for example, it should initiate this process and essentially self-destruct); all of these are related to injury and high stress, and are ‘designed’ (I can almost hear Darwin saying: “Careful now!” over my shoulder) to increase when the body undergoes trauma, so this genetic response to overall body death was predicted, to a degree, by the authors.

What they did not expect to find was an increase in the activity of several genes associated with foetal development, genes which had been silent and inactive since the initial development of the embryo but were now once more active for a final time; a kind of genetic second childhood. However, while at first glance you could imagine this activity to be some kind of desperate plan encoded in the genome as a last resort, there was sadly no regeneration or reversion of the cells to a state of youthful health. Instead, the authors proposed that the reason behind this out-of-time transcription of developmental genes could be the activation of other genes in the thanatotranscriptome which were responsible for the ‘unpacking’ of DNA, allowing the cell machinery to get at genes that had previously been locked up, perhaps for years.

All this genetic activity is significant because it indicates that there were somewhat surprising levels of energy and resources available to the cells of both species long after death had supposedly occurred; genes were still being transcribed on a detectable scale up to 96 hours after death in the zebrafish, and up to 48 hours in the mouse. In addition, the pattern of transcriptional activity over time seen in both species is unique to each. With much further study, it is possible that the post-mortem transcription landscape could be determined in humans as well, with potential uses in forensics and for organ transplants.

Ultimately, the authors concluded that, as this gene transcription could have no evolutionary purpose, the patterns seen, though non-random, are simply a result of natural energetic and chemical processes in an organism that is winding down; thermodynamics more than any underlying strategy is at work here. However, they did speculate on an intriguing question, asking: “what would happen if we arrested the process of dying by providing nutrients and oxygen to tissues?” Perhaps, for some cells, a kind of resurrection might be possible; they would be in a unique limbo-state, not having passed on, yet not quite living in the same way they had before.

However, whatever the future applications of and discoveries regarding this fascinating new field of biology, we can perhaps take a little comfort in the fact that there is a kind of life after death after all.

Further reading:

“Tracing the dynamics of gene transcripts after organismal death” – Noble et al. (2017) –http://rsob.royalsocietypublishing.org/content/7/1/160267

New Scientist article on the above paper – https://www.newscientist.com/article/2094644-hundreds-of-genes-seen-sparking-to-life-two-days-after-death/

How Stuff Works podcast covering the paper – http://www.stufftoblowyourmind.com/podcasts/undead-genes.htm

Wikipedia page on the Thanatotranscriptome – https://en.wikipedia.org/wiki/Thanatotranscriptome

#Biology #Genetics #MattAmbrose