It’s (not) alive! Zombie genes wake up after death

Brittney G. Borowiec
9 December 2016

Above: Image © antonbrand, iStockphoto

It’s a dreary autumn night. A scientist works on his experiment. The air crackles with electricity. He just knows he’s about to make a breakthrough! His surgical instruments flash in the eerie glow of his candle. He cuts the body. A dull yellow eye opens. The creature gasps and convulses. Frankenstein rises!

Scientists can’t bring people back from the dead just yet. However, they understand a lot more about death and dying than they did when Mary Shelley wrote her novel Frankenstein.

In fact, a 2016 study showed that some genes continue to be expressed after an organism dies. Researchers call these genes the thanatotranscriptome. Understanding the thanatotranscriptome has big implications for forensics (the scientific study of crime) and medical science.

Did you know? The term thanatotranscriptome comes from Thanatos, the ancient Greek version of the Grim Reaper.

Genes and gene expression

Genes are stretches of DNA that code for information. They’re expressed (activated) when special cellular machinery uses the information to produce a protein (or another gene product).

The first step in gene expression is called transcription. Transcription involves making a copy of the information in the DNA. This “cheat sheet” is sent to other parts of the cell to provide instructions about which proteins to make.

Enzymes are special compounds that speed up important chemical reactions. An enzyme called RNA polymerase reads the DNA and transcribes it into messenger RNA. Ribosomes use this RNA to build strings of amino acids. The strings are folded, modified and combined to create proteins for the body to use.

Proteins are the workhorses of a cell. Proteins can do jobs like speed up chemical reactions (enzymes), transport molecules around a cell or provide structure to a cell. Different proteins have different jobs.

Gene expression is tightly controlled to make sure it happens at the right place, time and level. For example, some proteins silence genes by binding to DNA. This blocks RNA polymerase from reading DNA and producing messenger RNA. Other protein complexes help bring all the cellular machinery together. This makes it easier for some genes to be transcribed.

Did you know? Many medical conditions are a consequence of improper expression of specific genes. Cystic fibrosis is one example.

“Zombie” genes come alive after death

But what happens after an organism dies? Does gene expression slowly fade out? Or does it stop all of a sudden? Do specific genes help shut down biological systems after death?

There’s an international team of researchers intrigued by these questions. In that 2016 study I mentioned in the introduction, they tracked the RNA levels of over 1000 genes in mice and zebrafish after death.

The RNA produced during transcription provides instructions to different parts of the cell. When scientists measure RNA levels, they can “intercept” these instructions. They can then figure out what a cell was doing at a specific point in time. For example, if they found a cell with increased expression of antibodies, they could guess that the cell was fighting off a bacterial infection.

As scientists expected, total RNA levels steadily declined from the time of death. This meant that complex molecules in the dead body were breaking down, and that the body’s energy stores were being drained.

That was true for most genes. But the RNA levels of some genes did the opposite! Their RNA levels increased for up to four days after death in zebrafish, and up to two days after death in mice.

So which genes live beyond the grave? The researchers focused on genes that fall into broad functional categories like stress response, immunity, inflammation, transport, development and cancer. They chose these categories because they include many genes that are common to both mice and fish. The researchers also suspected that some of these genes might not follow the general trend of declining RNA levels.

Many of the stress response and transport genes help make sure a cell has what it needs to function. This includes oxygen, sugars and ions. Scientists weren’t surprised that these genes became more active when the rest of the body starts to shut down. When the circulatory system stops, the body stops delivering oxygen and nutrients to the cells—and the cells react! Similarly, many of the genes related to immunity, inflammation and stress get activated in emergencies, like injury or death.

Many of the changes in RNA levels after death are likely due to the cell losing control of gene expression. For example, proteins that normally prevent RNA polymerase from reading DNA can break down quickly after death. This would allow RNA polymerase to transcribe genes that are usually silenced (shut off). Such genes would include ones that are important for cell development.

Did you know? There are between 20,000 and 25,000 human protein-coding genes. They account for less than two percent of all genetic material in the human genome.

Implications for forensics and medicine

In the late 1980s, DNA fingerprinting revolutionized forensics. It let investigators determine if a person had been at a crime scene by testing small tissue samples, like a strand of hair or a drop of blood or saliva.

Similarly, the thanatotranscriptome could completely change how investigators study dead bodies. Currently, there are many methods that help determine the time of death. Some are more accurate than others. However, the expression of the thanatotranscriptome could provide a way of pinpointing time of death that is more accurate than any of the current methods.

Indeed, in another 2016 study, scientists found that they could measure the expression of the thanatotranscriptome to precisely determine the time of death in zebrafish and mice.

The future of the thanatotranscriptome

Scientists have only just begun to delve into the spooky world of the thanatotranscriptome. In the future, it might inspire new techniques for organ transplants, forensics and molecular biology.

For example, the thanatotranscriptome could help scientists understand why transplanted organs are much more likely to develop cancer. Donor organs can spend hours outside a donor’s body before they are transplanted into a recipient. And the study discussed in this article found cancer-related genes expressed in the dead mice and zebrafish cells. If this expression also happens in humans cells, it could explain why transplanted organs are at higher risk for developing tumours.

I hope learning about the thanatotranscriptome doesn’t give you nightmares about zombie cells! But even if the article gave you a few chills, I also hope you understand why thanatotranscriptome research is more exciting than creepy. Not only does it have the potential to help murder investigators solve crimes, it could actually lead the way to some exciting medical discoveries.

Learn More!

Brittney G. Borowiec

I completed my undergraduate degree in Honours Biology (Physiology Specialization) at McMaster University, located a short trip down the 403 from my hometown of Mississauga, ON. I’m now a PhD candidate in the same department, studying how fish respond to different patterns of low oxygen stress. When I’m not volunteering for Let’s Talk Science, you can find me blogging about oceanography at Oceanbites.

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