Secret to Cancer Suppression Genes May Reside in Whale DNA

Scientists from Arizona State University are studying the genetic code of the humpback whale as well as other cetaceans—the mammalian group that includes whales, dolphins, and porpoises—in order to determine how their cancer defenses are so effective despite their weight and size.
 
The study included 9 international institutions, from the University of Groningen in the Netherlands to the Center for Coastal Studies in Massachusetts, which together studied the potential cancer suppression mechanisms in cetaceans. The investigators believed that their findings would reveal potential new targets for preventing cancer in humans, such as using the whale version of a protein that can stop cell proliferation to develop drugs that shrink tumors in humans.
 
Scientists focused on the phenomenon known as Peto’s Paradox, named after Richard Peto, which observes that at the species level, the incidence of cancer does not appear to correlate with the number of cells in an organism. Following this logic, scientists determined that a suitable organism to study would be a humpback whale, which lives longer and is much larger than many animals.
 
The researchers worked under a federal research permit to obtain skin samples of an adult female humpback whale off of the coast of Massachusetts, named Salt, who has one of the most well-documented life histories of any individual humpback whale. The team sequenced and assembled Salt’s genome, spanning approximately 2.7 billion base pairs, and her RNA.
 
After comparing the whale’s genome with other mammals, including the blue whale and fin whale, they found that certain parts of the whale genome have evolved faster than other mammals. These parts of the whale genome contain genes that control the cell cycle, cell proliferation, and DNA repair, which are essential for normal cell function. In human cancers, many of these genes are mutated. The whale genome also evolved many duplications in tumor suppressor genes.
 
According to the press release, the scientists discovered that these “housekeeping” genes are evolutionarily conserved and normally prevent cancer, enabling these species to grow to their large sizes. Furthermore, despite these cancer-related parts of whales’ genomes evolving faster than other mammals, whales have accumulated far fewer DNA mutations in their genomes over time than other mammals, which suggests that they have slower mutation rates, according to the study. This slow rate of change may limit whales’ exposure to cancer-causing somatic mutations.
 
The next step for the team of researchers to better understand the cancer suppression phenotype is to experiment with whale cell lines, which will provide important functional validation of the team’s genomic results. This will be the first step in generating whale-derived human cancer drugs.
 
Reference
How whales defy the cancer odds: Good genes [news release]. Published May 10, 2019. https://www.sciencedaily.com/releases/2019/05/190510091342.htm. Accessed May 13, 2019.



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