Whales: gigantism and cancer suppression evolved concurrently
Humpback genome adds to growing understanding of ‘Peto’s Paradox’. Andrew Masterson reports.
As whales evolved to become gigantic, the genetic changes needed to accomplish the feat were accompanied by others that drastically reduced the primary danger of growing huge: cancer.
That’s the conclusion reached by a team of researchers led by Marc Tollis of the Biodesign Institute at Arizona State University in the US and published in the journal Molecular Biology and Evolution.
In some respects, the risk of cell mutations that develop into cancer is a brute numbers game, broadly conditional on the number of cells in any given organism, not merely at any given moment, but across lifespan.
Large whales, such as the blue (Balaenoptera musculus) and the humpback (Megaptera novaeangliae), have around 1000-times more cells than a human and can live for 90 years or more. On the figures, therefore, they should be particularly susceptible to cancer.
However, as far as scientists have been able to determine, they are not. Indeed, all gigantic mammals – elephants, for instance – appear to have lower rates of cancer than their cell counts should suggest.
This situation, acknowledged for years, is known as Peto’s Paradox, named after a researcher who in 1975 showed that an increase in cancer occurrences in mammals as they age was due to the cumulative effects of lifetime dose and not any intrinsic effect of ageing.
In the latest research, Tollis and colleagues constructed – for the first time – the complete genome of a humpback whale, and then compared it to existing genomes for 10 other species.
The results confirmed earlier research that found that gigantism is linked to the duplication of many genes that are associated with cell function, DNA repair and ageing.
Bowhead whales (Balaena mysticetus), for instance, have been estimated to live for at least 200 years, and their genome shows positive selection of a gene called ERCC1, which is an important component of the DNA repair pathway. The species also has duplications in other genes that influence gene repair and cellular growth.
Similar duplications were found in the genomes of other species.
“Altogether, these results suggest that the genomes of larger and longer-lived mammals may hold the key to multiple mechanisms for suppressing cancer, and as the largest animals on Earth, whales make very promising sources of insight for cancer suppression research,” the researchers write.