NYSCF Investigator Looks To Animal Genomes To Learn More About Human Disease
Elephants don’t get cancer. Well, they do, but not nearly at the same rate as other mammals. In a way, this is odd because cancer is brought on by uncontrolled cell division and DNA replication errors, and elephants, being the largest land mammal, have a ton of cells. The more cells, the higher the risk that one of these mistakes will occur. So why are they so healthy?
It has been proposed that because they are at a high risk, elephants have acquired certain mechanisms for cancer prevention, but these mechanisms aren’t yet fully understood. If we knew more about them, however, this information could help us design treatments for cancer in humans.
Researchers from the University of Utah led by NYSCF Investigator Christopher Gregg, PhD, were interested in identifying aspects of animal genomes that lead to certain clinically relevant characteristics (like cancer resistance). The researchers focused on elephants, orcas, dolphins, bats, naked mole rats, and ground squirrels because each is closely associated with characteristics specific to cancer, hand and feet abnormalities, cornea development, blood clotting disorders, albinism/Leopard Syndrome, or glaucoma.
The researchers were searching these animals’ genomes for something called “accelerated regions”, or “ARs”. ARs are regions of the genome that, while generally the same across most mammals, are different in a few of them and might give rise to a distinct characteristic of that animal (like wings or fur coloring).
In the elephant genome, researchers found an increased number of ARs at two locations: one containing the FANCL, VRK2, and BCL11A genes and one containing genes that respond to DNA damage in blood cells. The ARs found in these locations could contribute to elephants’ cancer resistance by making their DNA repair mechanisms more efficient and lowering their risk for mutations.
The next step is to look into how these findings can be translated into research on human cells. We can now engineer human cells to contain elephant genome sequences and see whether this helps protect them from mutation. We can also locate the human equivalent of the elephant AR, delete or modify it, and see if it affects how cells behave. Lastly, we can study how environmental factors might contribute to human expression of the AR.