Elephants' 'zombie gene' may give cancer insights

For their large body size, elephants should get cancer a lot more often than they do – now a new study has found out why. And this may help in our understanding of cancer.

Researchers at the University of Chicago in Illinois suggest that elephants have evolved to protect themselves from cancer by resurrecting a copy of an ancient tumour suppressor gene LIF6, that had become dormant. They call it a 'zombie gene'.

'It might tell us something fundamental about cancer as a process. And if we're lucky, it might tell us something about how to treat human disease,' senior author Dr Vincent Lynch told the New York Times.

The LIF6 gene can kill cells in response to DNA damage and prevent the accumulation of errors in the genome that lead to uncontrolled cell proliferation and, therefore, tumour formation.

The gene is expressed by the cells of most mammals, including humans, where it is usually present as a single copy. The ancestors of the modern elephant accumulated ten copies of the LIF gene, known as pseudogenes – dormant genes whose functionality is lost. Among these extra copies, elephants appear to have brought one of them back to life.

'I was sitting at my computer, and I thought: "let me just look at the elephant genome and see if they have extra tumour suppressors",' said Dr Lynch, senior author of the study and an evolutionary biologist. 'It turns out they have lots. And then I had something to tell the class.'

The finding may help explain an observation known as the 'Peto paradox' that has long puzzled scientists. Large animals, like elephants, have more cells than small animals: a higher number of cells means a higher number of cell divisions, which increases the chances of acquiring cancer-related mutations.

This applies within members of the same species, but paradoxically not across species. In other words, taller humans are more likely to develop tumours than shorter ones, but elephants are not more susceptible to tumours than humans.

Previous studies identified other genes that help fight tumours, of which copies seemed to have accumulated during the evolution of the elephant lineage. One of these genes is p53 – often described the 'guardian of the genome'. Analysing 53 different mammalian genomes, Lynch's team found that p53 activated the expression of LIF6 in elephant cells in vitro in response to DNA damage. The LIF6 proteins then triggered the release of toxic molecules from the mitochondria of the cells, causing cell death.

The results 'offer up another avenue of research, another piece of the puzzle, in how nature decreases cancer, and could help us in finding creative ways to treat and perhaps one day prevent cancer' said paediatric oncologist, Dr Joshua Schiffman at the University of Utah in Salt Lake City, who has also studied cancer in elephants and was not involved in the study.

The new research was published in Cell Reports.