‘Undead’ genes come alive days after life ends

Although this rat is dead, its genes may still be functioning, a new study reveals.

V. Rachai/iStockphoto

‘Undead’ genes come alive days after life ends

Does death really mean the end of our existence? Great thinkers from Plato to Blue Öyster Cult have weighed in on the question. Now, a study shows that at least one aspect of life continues: Genes remain turned on days after animals die. Researchers may be able to parlay this postmortem activity into better ways of preserving donated organs for transplantation and more accurate methods of determining when murder victims were killed.

Before you ask, microbiologist Peter Noble of the University of Washington, Seattle, and colleagues were not trying to find out what allows zombies to stalk Earth and slurp the brains of the unwary. Instead, the scientists wanted to test a new method they had developed for calibrating gene activity measurements. Their research had already taken a morbid turn—2 years ago they published a paper on the abundance of microbes in different human organs after death—and they decided to apply their method to postmortem samples. “It’s an experiment of curiosity to see what happens when you die,” Noble says.

The headline of this study is that we can probably get a lot of information about life by studying death.

Peter Noble

Although scientists analyzing blood and liver tissue from human cadavers had previously noted the postmortem activity of a few genes, Noble and colleagues systematically evaluated more than 1000. The team measured which of these genes were functioning in tissues from recently deceased mice and zebrafish, tracking changes for 4 days in the fish and 2 days in the rodents.

At first, the researchers assumed that genes would shut down shortly after death, like the parts of a car that has run out of gas. What they found instead was that hundreds of genes ramped up. Although most of these genes upped their activity in the first 24 hours after the animals expired and then tapered off, in the fish some genes remained active 4 days after death.

Many of these postmortem genes are beneficial in emergencies; they perform tasks such as spurring inflammation, firing up the immune system, and counteracting stress. Other genes were more surprising. “What’s jaw-dropping is that developmental genes are turned on after death,” Noble says. These genes normally help sculpt the embryo, but they aren’t needed after birth. One possible explanation for their postmortem reawakening, the researchers say, is that cellular conditions in newly dead corpses resemble those in embryos. The team also found that several genes that promote cancer became more active. That result could explain why people who receive transplants from the recently deceased have a higher risk of cancer, Noble says. He and his colleagues posted their results on the preprint server bioRxiv last week, and Noble says their paper is undergoing peer review at a journal.

“This is a rare study,” says molecular pharmacologist Ashim Malhotra of Pacific University, Hillsboro, in Oregon, who wasn’t connected to the research. “It is important to understand what happens to organs after a person dies, especially if we are going to transplant them.” The team’s approach for measuring gene activity could be “used as a diagnostic tool for predicting the quality of a transplant.”

In an accompanying paper on bioRxiv, Noble and two colleagues demonstrated another possible use for gene activity measurements, showing that they can provide accurate estimates of the time of death. Those results impress forensic scientist David Carter of Chaminade University of Honolulu. Although making a time of death estimate is crucial for many criminal investigations, “we are not very good at it,” he says. Such estimates often rely on evidence that isn’t directly connected to the body, such as the last calls or texts on the victim’s cellphone. Noble and his colleagues, Carter says, have “established a technique that has a great deal of potential to help death investigation.”

A mouse or zebrafish doesn’t benefit, no matter which genes turn on after its death. The patterns of gene activity that the researchers observed may represent what happens when the complex network of interacting genes that normally keeps an organism functioning unwinds. Some genes may turn on, for example, because other genes that normally help kept them silent have shut off. By following these changes, researchers might be able to learn more about how these networks evolved, Noble says. “The headline of this study is that we can probably get a lot of information about life by studying death.”