Elephants hardly ever get cancer, and we may finally know their secret
| Elephant cancer mortality is under 5 percent; in humans, it’s between 11 and 25 percent
| Mike McRae, Science Alert – For years, scientists have tried to figure out why elephants are so good at not getting cancer.
New research suggests their amazing ability involves resurrecting a gene from the dead and giving it a task to kill cells.
Experiments conducted by researchers from the University of Chicago have finally unveiled the mechanism behind the pachyderm’s uncanny ability to avoid tumors, helping us better understand a riddle known as Peto’s paradox.
It goes like this: the more cells an animal has, the more opportunities it should have to develop a tumor.
Within any given species, this appears to ring true. Larger breeds of dog seem to have a greater predisposition to cancer than smaller ones, for example.
But when comparing animals of different species, the concept falls down. There is zero correlation between the volume of an animal’s body or its relative lifespan and the chance of cancer popping up among all those cells.
Named after epidemiologist Richard Peto, the paradox has confused biologists for decades. Clearly evolving to be bigger has meant finding more efficient ways to make sure cancer didn’t also take advantage.
Elephants are a textbook example. In 2015, researchers estimated their cancer mortality rate stood at just under 5 percent, compared with the 11 to 25 percent for the relatively puny human body.
That study also found a potential clue to the elephant’s anti-cancer superpower in the form of a gene called TP53. Like most anti-cancer genes, it makes a product that detects DNA damage and tells the cell to either fix it or close shop.
Most mammals have two copies of the gene. Elephants have twenty, suggesting they’re well prepared to spot the threat of cancer early and act on it at a moment’s notice.
Understanding the complex ways such tumor-suppressing genes work in large, long-lived animals isn’t easy … Read more at Science Alert.
Scientific study of elephants’ special anti-cancer gene: Cell Reports
Large-bodied organisms have more cells that can potentially turn cancerous than small-bodied organisms, imposing an increased risk of developing cancer.
This expectation predicts a positive correlation between body size and cancer risk; however, there is no correlation between body size and cancer risk across species (“Peto’s paradox”).
Here, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto’s paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions.
LIF6 is transcriptionally upregulated by TP53 in response to DNA damage and translocates to the mitochondria where it induces apoptosis.
Phylogenetic analyses of living and extinct proboscidean LIF6 genes indicates that its TP53 response element evolved coincident with the evolution of large body sizes in the proboscidean stem lineage.
These results suggest that refunctionalizing of a pro-apoptotic LIF pseudogene may have been permissive (although not sufficient) for the evolution of large body sizes in proboscideans.
The risk of developing cancer places severe constraints on the evolution of large body sizes and long life spans in animals.
If all cells have a similar risk of malignant transformation and equivalent cancer suppression mechanisms, organisms with many cells should have a higher risk of developing cancer than organisms with fewer cells.
Similarly, organisms with long life spans have more time to accumulate cancer-causing mutations than organisms with shorter life spans and therefore should also be at an increased risk of developing cancer, a risk that is compounded in large-bodied, long-lived organisms.