In many ways, cancer is a disease of chance. Certain habits – such as smoking and substance abuse – or genetic predispositions will increase that chance, but every time a cell replicates there is a chance of something going wrong, causing cells to reproduce out of control and develop into cancers.
Therefore, it seems logical that two things will increase the chance of developing cancer: the number of cells that replicate, i.e. the size of the organism; and how long the organism lives, which provides more replications to go awry. But if that’s the case, why don’t elephants get cancer all the time?
In a new study published in the journal eLife, scientists have discovered that elephants – and likely other large land mammals – have evolved an entire arsenal of tumor suppression genes that stave off aberrant tumor cells. Copies of these genes are found in greater numbers than in other animals, and may have evolved alongside their gigantic bodies to keep the species growing.
The authors now believe it’s possible that secrets to new cancer therapies may lie in the genomes of larger animals.
“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,” said Juan Manuel Vazquez, a postdoctoral researcher at the University of California, Berkeley, in a statement.
The study involved exploring the genomes of elephants in search of tumor suppressor genes, to discover whether they have extra copies that may enhance their protection. Previous research has highlighted that elephants have duplicated a well-known and important tumor suppressor gene, TP53, which prevents cells from uncontrolled division. To find out more, the researchers wanted to examine if this was isolated to TP53 or part of a wider evolutionary trend.
“Is the trend general? Or is the trend specific to one gene? We found that it was general: 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.” said Vincent Lynch, assistant professor of biological sciences at the University at Buffalo.
Interestingly, elephants are not the only ones with an innate defense against cancer. Other afrotherians (including elephant shrews, aardvarks, and dugongs) also appear to have extra copies of tumor suppressor genes. Despite being relatives of elephants, many of these animals are quite small, suggesting the duplications arose before or during the evolution of huge bodies.
However, elephants certainly came out on top. Throughout the Proboscidea (African bush elephants, Asian elephants, and African forest elephants) genomes they tested, the researchers identified 12 uniquely enriched pathways directly linked to cancer. These were only found in large-bodied mammals, likely aiding the development of their bulk.
Unfortunately, having extra copies of some tumor suppressor genes may also be detrimental to the animal, representing an evolutionary trade-off of sorts. While they may defend against cancer, increased expression of TP53 in mice is associated with various other diseases, such as the early-aging disease progeria. The researchers believe that this does not happen in elephants as the duplications are under sufficient gene regulation to prevent overexpression, preventing the negative effects.