A new study published on August 14 in Cell Reports has identified a new gene that may explain why elephants rarely get cancer. The LIF6 gene seems to alter the way elephant’s cells respond to cancer-inducing DNA damage and may protect them from cancer by preventing cancerous cells from forming in the first place. The gene was aptly named the “zombie gene” since it was resurrected at some point during the evolution of the modern elephant and when active, rapidly kills any potentially cancer-inducing cells around it.
Cancers arise due to mutations in the DNA of cells that trigger the development of tumours by causing uncontrollable growth and division of cells. Larger animals have more cells and longer lifespans and therefore ought to be more susceptible to cancer but surprisingly this is not the case in many large mammals, such as elephants and whales. The fact that there is no correlation between body size and cancer rates among animal species has puzzled scientists for decades, a phenomenon referred to by biologists as Peto’s paradox.
Now it seems there may be an explanation: larger animals may simply have more cancer-fighting defences. Recent work led by geneticist Vincent Lynch from the University of Chicago, USA, discovered that a particular LIF gene ― part of a family of genes that produces cancer-suppressing proteins that prevent tumour growth ― has in fact been reactivated in one species of elephant and may be responsible for their resistance to cancer. Other mammals have multiple copies of LIF genes but in most species, these are pseudogenes― mutated or inactive copies of a normal gene that cannot be used by cells unless reanimated somewhere along the evolutionary process.
The discovery was made by examining the elephant genome. Researcher’s noticed the presence of several copies of LIF genes, nearly all of them inactive except for one, LIF6, which was likely reactivated during the evolutionary development of the modern Loxodonta africana, also known as the African bush elephant. When LIF6 expression was blocked in elephant cells, those with DNA damage survived in the same way damaged cells of animals with inactive LIF genes do, whereas activating the LIF6 gene in mice cells led to the immediate death of cells with DNA damage.
Another three genes, FANCL, VRK2, and BCL11A, identified earlier this year as being involved in the cancer resistance of elephants may also play an important role (2). Furthermore, other large animals, such as whales, that also do not seem to get cancer, don’t have the zombie gene which suggests their cancer resistance may be based on other tumour suppressing genes or functions.
While the activated LIF6 gene is currently believed to be unique to elephants, researchers hope they may be able to reactivate cancer-suppressing genes in human cells, thus offering new methods of fighting cancer. However, further research is needed to determine the feasibility of using this type of approach as a therapeutic treatment in humans.
(1) Vazquez, J.M. et al. A Zombie LIF Gene in Elephants Is Upregulated by TP53 to Induce Apoptosis in Response to DNA Damage. Cell Reports (2018). DOI: 10.1101/187922
(2) Ferris, E. et al. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance. Cell Reports (2018). DOI:10.1016/j.celrep.2018.02.008