“Zombie gene” protects elephants from cancer finds study

By Dr. Ananya Mandal, MDAug 14 2018

A new study has found that elephants do not get cancers as frequently as other animals because of a special gene that they carry.

Researchers led by Vincent J. Lynch, an evolutionary biologist at the University of Chicago said that their team found that the elephants carry this unique gene that can kill all the cells that have damaged DNA. Cells with mutated and altered or damaged DNA are ones that multiply to give rise to cancers. They noticed that with evolution, this helpful gene became dormant and in elephants alone a bit of this gene still remains functional. They call it the “zombie” gene that has been resurrected. The study appeared in the latest issue of the journal Cell Reports.

Image Credit: Willyam Bradberry / Shutterstock

According to Lynch, deeper understanding of this phenomenon could help researchers find new drugs to fight cancer. He explained that it could help them understand cancer as a process and eventually how to combat it. Since the 1970’s the lack of cancers in these large animals has been studied extensively. Genetic studies to understand why this happens are a recent development.

Earlier, the p53 gene was the only candidate that was focussed upon. This gene – p53 makes a protein that can sense when a cell has a damaged DNA. The protein on detecting a cell with damaged DNA switches on several other genes.

This stimulates the cell to take two courses of action – either repair the damage or commit suicide to prevent the mutation from spreading to its progeny. Dr. Lynch and his colleagues a few years earlier found that elephants have unusual p53 genes.

Humans have a single copy of this gene but elephants seemed to have 20 copies of this gene. Same findings were seen independently by researchers at the University of Utah. Both teams noticed that these p53 genes respond with more aggression when there encounter a cell with damaged DNA. As soon as they encounter a cell with damaged DNA, they do not initiate a repair but go for cell death.

The study and search for these genes continued at Lynch’s lab till they found another gene. This is called the LIF6. This gene is found only in elephants. They found that when there was DNA damage, the p53 genes in the elephants switched on the LIF6. This gene makes LIF6 proteins. These proteins attack the cell’s mitochondria that provide energy to the cell for its functions. The mitochondrial walls are cut open by these proteins and their molecules leak out. These molecules from the mitochondria are toxic to the cell and end up killing the cell.

Researchers looked at the evolution of LIF6 and found that all mammals carry a similar gene called the LIF. These send out cell signals. However humans and other animals seemed to have a single copy of this gene. Elephants and their close evolutionary relatives like the manatees have several copies of this gene. Elephants were found to have 10 copies of this gene. These multiple copies arose due to mutations in the manatees’ and elephants’ ancestors around 80 million years ago they speculated. Thus the additional copies of the LIF genes in elephants and manatees are different from the original ones. They do not carry a bit of the DNA that acts as an on-off switch. This made these genes incapable of making LIF proteins. With time one of the ten LIF genes in the elephants that were dead came back to life like a zombie and regained its switch. This is called the LIF6 gene. Now this LIF6 gene with a switch could be activated by the p53 gene and initiate damaged cell killing.

Dr. Lynch said that ancestors of elephants developed extra copies of the p53 gene and at the same time resurrected the LIF6 gene causing them to be able to resist the cancers.

Reference: https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31145-8