What Happens to Genes After Death

How this question was studied

Before we become ourselves, before we have a brain, our cells are already actively working: they divide, differentiate, form "bricks", which will then be folded into a whole organism. But it turned out that they not only anticipate ourselves, but also outlive us.

It all started with the studies of Thanatotranscriptome: genes actively expressed after organismal death by genetics Alexander Pozhitkov. In 2009, he undertook to study the RNA of zebrafish after their death. The embryos of these tropical fish are transparent and ideal for observation, which is why they are kept in many laboratories. Pozhitkov placed the fish in ice-cold water, which led to their death, and then returned them to the aquarium with their usual water temperature - 27, 7 ℃.

Over the next four days, he took several fish out of the aquarium, frozen them in liquid nitrogen, and studied their messenger RNA (mRNA). These filamentous molecules are involved in the synthesis of proteins. Each strand of mRNA is a copy of a piece of DNA. Then Pozhitkov also investigated the mRNA of mice.

Together with biochemist Peter Noble, he analyzed the activity of mRNA after death and discovered a surprising fact. In both fish and mice, protein synthesis declined, as expected. However, judging by the amount of mRNA, the process of transcription (the transfer of genetic information from DNA to RNA) is amplified in about one percent of genes.

Some genes continued to work even four days after the death of the organism.

Other scientists examined human tissue samples and discovered hundreds of genes that remain active after death. For example, after four hours, the expression (that is, the conversion of hereditary information into RNA or protein) of the EGR3 gene, which stimulates growth, increased. The activity of other genes is fluctuating, including CXCL2. It codes for a protein that signals the white blood cells to travel to the site of inflammation during infection.

This is not just the result of different gene transcriptions being completed at different rates, says study director Pedro Ferreira. Some kind of process actively regulates posthumous gene expression.

After the death of an organism, the first to die are the most important, most energy-intensive cells - neurons. But peripheral cells continue to do their job for days or even weeks, depending on the temperature and degree of decomposition of the body. Researchers succeeded in Recovery of fibroblast-like cells from refrigerated goat skin up to 41 d of animal death to extract live cell cultures from goat ears 41 days after animal death. They were in the connective tissue. These cells do not require a lot of energy, and they survived 41 days in a regular refrigerator.

At the cellular level, the death of an organism does not matter.

It is not yet known what exactly causes posthumous gene expression. Indeed, after death, oxygen and nutrients cease to flow into the cells. A new study by Noble and Pozhitkov, Distinct sequence patterns in the active postmortem transcriptome, may shed light on this question.

Using original data from fish and mice, Noble found that the mRNA that was active after death was different from other mRNA in cells. About 99% of RNA transcripts in cells are rapidly destroyed after the death of the organism. The remaining 1% contains certain nucleotide sequences that bind to molecules that regulate mRNA after transcription. This is probably what supports the posthumous gene activity.

Scientists believe that this mechanism is part of the cellular response when the body can recover from serious injury. It is possible that cells in death throes are trying to "open all the valves" so that certain genes can be expressed. For example, genes that respond to inflammation.

Why is it important

Understanding the mechanisms behind postmortem gene activity will affect organ transplants, genetic research, and forensics. For example, Pedro Ferreira and his colleagues were able to accurately determine the time of death of an organism, relying only on posthumous changes in gene expression. This can be useful when investigating murders.

However, in this experiment, the scientists knew that the tissues under study belonged to donors without pathologies and were stored in ideal conditions. In real life, many factors can affect RNA transcription, from diseases in the body to ambient temperature and the time elapsed before sampling. So far, this research method is not ready for use in legal proceedings.

Noble and Pozhitkov believe these discoveries will also be useful in organ transplants.

The organs of donors are outside the body for some time. Perhaps the RNA in them begins to send the same signals as in the case of death. According to Pozhitkov, this may affect the health of patients who have received a new organ. They have an increased incidence of cancer compared to the general population. Perhaps the point is not in the drugs that suppress the immune system that they have to take, but in the postmortem processes in the transplanted organ. There is no exact data yet, but researchers are considering storing organs for transplantation not in the cold, but on artificial life support.