The mystery is not how elephants came to have an extremely low risk of cancer, it’s why. Research has already answered the how—elephants possess extra copies of tumor-suppressor genes, leaving the species essentially cancer-resistant. But why?
All things being equal, large, long-living mammals should have the highest risk of cancer. Tumors grow when genetic mutations cause individual cells to reproduce too quickly. A long life creates more opportunities for cancerous mutations to arise. So, too, does a massive body: big creatures with many more cells should develop tumors more frequently—but elephants do not.
Why is that?
To answer that question, Vincent Lynch from the University at Buffalo and Juan Manuel Vazquez from UC Berkeley examined the genomes of not only the elephant species, but fellow Afrotherians, as well. Afrotherians are a clade of mostly small-bodied mammals of African origin, including Cape golden moles, elephant shrews, rock hyraxes, manatees, extinct woolly mammoths, extinct mastodons and more.
Previous research by the scientists established that elephants possess TP53, a well-known tumor suppressor gene. This new study, published in eLife, expanded upon that, showing that the duplication of tumor suppressor genes is also common among elephants' living and extinct relatives. The researchers even found extra copies of tumor suppressors in a group of mammals called Xenarthra, who are closely related to Afrotherians.
Even with all these mammals seemingly protected from cancer, the study results indicate elephants live with enhanced safeguards. The elephant genome possesses unique tumor suppression duplications that the other mammals did not through genes involved in DNA repair, resistance to oxidative stress, cellular growth, aging and death.
“Elephants have lots and lots and lots of extra copies of tumor suppressor genes, and they all contribute probably a little bit to cancer resistance,” explained Lynch.
The scientists were surprised to see the duplicate tumor suppressor genes across the entirety of the elephant species family tree, especially in the smaller-bodied mammals. They unexpectedly found that the duplication of genes occurred at various points throughout the evolution of Afrotheria, regardless of body size.
“These data suggest that duplication of tumor suppressor genes is pervasive in Afrotherians and preceded the evolution of species with exceptionally large body sizes,” the authors write.
In fact, the genes may have actually aided the evolution of ancient large-bodied mammals within the Afrotherians and Xenarthrans groups.
"If you pick a weird mammal, there's a good chance that it will be in these groups: armadillos, aardvarks, sloths, anteaters, etc.,” said Lynch. “We found that within these groups, the ones we studied all seem to have extra copies of tumor suppressor genes. That may be why in the last Ice Age, there were giant sloths and ancient mega-armadillos. There's even an extinct species of manatee relative called the Steller's sea cow that was elephant-big. Extra copies of tumor suppressors may have helped all of these animals get really, really big."
Not only big, but cancer-resistant, as well.
“By determining how big, long-lived species evolved better ways to suppress cancer, we can learn something new about how evolution works and hopefully find ways to use that knowledge to inspire new cancer treatments,” Vazquez concluded.
Photo: Artist's illustration of species within the taxonomic order Proboscidea, which includes elephants. Credit: Liam Elward