All kinds of animals are at risk of developing cancer, which has a problem since the dinosaurs. It often starts when mutations occur in DNA, which has to be copied every time cells divide, a frequent event. Those mutations can lead to unregulated cell growth - cancerous tumor formation. Weight and age also influence the risk of cancer, suggesting that large, long-lived creatures like elephants or whales should have the highest rates of cancer. But elephants and whales are actually less likely to get cancer than most animals. Assistant Professor Marc Tollis, of the School of Informatics, Computing, and Cyber Systems at Northern Arizona University, wanted to understand why. He and a team of researchers took a deep dive into cetacean genomes (which include dolphins, porpoises, and whales) to learn more.
After painstaking work collecting the material and obtaining the DNA from a humpback whale, the investigators found that some regions of the whale genome have evolved faster than they have in other mammals. Those regions contain genes that are involved in DNA repair and controlling cell division and growth; these same genes are often mutated in human cancers. The whale genome also contains many copies of tumor-suppressing genes.
“This suggests that whales are unique among mammals in that in order to evolve their gigantic sizes, these important ‘housekeeping’ genes, that are evolutionarily conserved and normally prevent cancer, had to keep up in order to maintain the species’ fitness,” Tollis said.
“We also found that despite these cancer-related parts of whale genomes evolving faster than other mammals, on average whales have accumulated far fewer DNA mutations in their genomes over time compared to other mammals, which suggests they have slower mutation rates,” he added. The findings have been reported in Molecular Biology and Evolution.
Whales are massive and live relatively long lives. While having more cells in the body that divide for a longer period of time should make them more susceptible to cancer, in a phenomenon known as Peto’s Paradox, they are not. Now that we know more about why that is, the researchers want to use their work to help develop better preventions or therapeutics for human cancers.
“Nature is showing us that these changes to cancer genes are compatible with life. The next questions are, which of these changes is preventing cancer, and can we translate those discoveries into preventing cancer in humans?” said co-senior study author Carlo Maley, a cancer evolutionary biologist from ASU’s Biodesign Institute.
“Our goal is not only to get nature to inform us about better cancer therapies but to give the public a new perspective of cancer,” Tollis said. “The fact that whales and elephants evolved to beat cancer, and that dinosaurs suffered from it as well, suggests that cancer has been a selective pressure across many millions of years of evolution, and it has always been with us. Our hope is that this may change people’s relationship with the disease, which can be painful and personal. It also helps provide even better appreciation for biodiversity. In our current sixth mass extinction, we need all the reasons for conservation that we can get.”