Elephants have a zombie gene that comes back to life to fight cancer
Elephants and cancer
Very few elephants die of cancer. Fewer than than five per cent of captive elephants die from the disease, compared to the roughly 17 per cent of humans who die of cancer. This is a bit of a paradox. Elephants are large, and have something like 100 times as many cells in which potential mutations might arise that could cause cancer.
Researchers, including Dr. Vincent Lynch, an assistant professor of human genetics at the University of Chicago, have recently discovered what might be the reason.
One part of the key is a gene called TP53 that exists in humans and many animals. This gene is a master tumour supressor, and recognizes damaged DNA cells which it then tags for destruction. Damage to DNA is a precursor to cancer. Humans have one copy of this gene, but the researchers discovered that that elephants have 20 copies of the P53 gene.
Zombie genes in elephants
While studying TP53 genes in elephants, the researchers made another surprising discovery. They found a former nonfunctioning gene — or pseudogene — that has been reactivated by TP53. The so-called zombie gene, LIF (leukemia inhibitory factor) evolved in elephants 25 to 30 million years ago, around the same time they began to get very large.
The zombie gene quickly helps kill damaged DNA that can lead to cancer. Elephants have eight such genes, but only one, LIF6, has been brought back to life.
"We call the gene a zombie gene because when you do the evolutionary analysis, it looks like all the ancestral … extra copies of LIF are dead genes. This one extra copy comes back to life in elephants and when it comes back to life and gets turned on, it causes elephant cells to kill themselves," Lynch said.
When cells with damaged DNA kill themselves, cancer can't take hold.
Cancer and size
Larger animals tend to live longer, but have more time and opportunity to accumulate cancer-causing mutations. Learning more about elephants and their low rates of cancer may provide insight into why other large mammals, like whales, are also resistant to the disease.
But size does not always matter; naked mole rats as well as some bats are also known to be protected against cancer.
The new findings show why it's so important to study nature, said Dr. Joshua Schiffman, a pediatric oncologist and a professor of pediatrics at the University of Utah. Along with the TP53 cancer-fighting mechanism in elephants, the zombie genetic approach has taken over 55 million years to develop and be perfected, Schiffman said.
It may offer some important clues for human patients.
"The more we scratch below the surface, the more we begin to understand about different biological and genomic mechanisms working together in the elephant to avoid cancer," said Schiffman, who was not involved in Lynch's study but has investigated TP53 in elephants.
If LIF6's contribution to cancer protection is confirmed then it could help physician-scientists in their search for ways to imitate the protection during drug development, he added.