Elephants, I think it is almost needless to say, are big animals. Yet despite being so massive, and thus being made up of many more cells than humans, their rate of cancer is much lower than we would expect. It is now thought that these big beasts have some form of genetic protection against cancer, and one such mechanism has been dubbed the “zombie gene”.
As cells replicate and divide, the DNA they hold can mutate as it is duplicated. This is the basis of cancer, as some of these mutations can cause cells to proliferate and grow uncontrollably, forming tumors. In effect, this is a numbers game, as the more cells divide, the higher the chance that a dangerous mutation will emerge.
Since the 1970s, this process has interested biologists, as it should mean that the larger and longer-lived an animal, the higher the chance its DNA will mutate and cause cancer, due to a greater number of cells dividing over a longer period of time. Yet studies of captive elephants that have died of natural causes have found that they display a consistently lower rate of cancer than expected for their longevity and size.
One estimate suggests that only 5 percent of the pachyderms get cancer, compared to some 10 percent in humans. A similar relationship holds with whales, and the phenomenon is known as Peto’s Paradox after the guy who first formulated it in 1977, Richard Peto.
Over the past few years, researchers have now been edging closer to answering what might be helping elephants stave off cancer, and there's hope that what is learned from the animals could be applied to humans, or at least help inform doctors. One such clue is the fact that elephants have duplicated a gene known as p53, one role of which is partly to suppress tumor cells. But it doesn’t stop there.
New work this year has started to unravel the role of another gene known as LIF which in elephants, and in their relatives such as hyraxes and aardvarks, has been duplicated up to 11 times. But fascinatingly, only the sixth copy, LIF6, seems to be working, and only in concert with the other duplicated p53 genes. It turns out that this combination makes any tumor cells more likely to commit cell suicide, known as apoptosis, by causing the mitochondrial membrane to leak.
What's interesting about all this, though, is that the LIF genes in the elephant’s relatives are all thought to be inactive, as they seem to have parts missing, making them non-functional. Because of this, the researcher who discovered the clearly working LIF6 called it the zombie gene, as it has seemingly woken up from the dead.
[H/T: Quanta Magazine]