Why Whales Could Hold the Key to Cancer Resistance

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 by Hannah Watts


Baleen whale

When it comes to disease research, there is arguably one question that comes up a lot: Why do larger organisms seem more prone to developing gene mutations leading to cancer and cell death compared to smaller ones? The simple answer could lie in the fact that larger organisms have more cells, leading to increased cell divisions and a higher likelihood of DNA damage and mutations that can turn healthy cells into cancerous ones.

However, there exists an important exception to this rule: Whales. Cetaceans (the infra order of aquatic mammals that include whales, dolphins and porpoises) are the largest and longest-living mammals on Earth and have, according to scientists, appeared to have evolved mechanisms to resist diseases such as cancer.

Research conducted at the Universidad Austral de Chile delved into the role of 1077 TSGs (tumour suppressor genes) in the longevity and cancer-resistant adaptations of cetaceans. TSGs play a crucial role in the body's anti-cancer responses, involving DNA damage repair, cell cycle regulation, and apoptosis. Mutations in TSGs can lead to cancer, and while humans share 99% of these genes with whales, the remaining 1% holds something special.

The study focused on two main lineages: baleen whales (like bowhead whales) and toothed whales (such as orcas, belugas, and dolphins). By sequencing the DNA of different species within these lineages, researchers could trace genetic differences resulting from evolution. They discovered a positive selection in the ancestors of cetaceans within the CXCR2 gene, a critical regulator of DNA damage, tumour dissemination, and the immune system.

In baleen whales, six genes showed positive selection related to cancer-related diseases such as breast carcinoma, lung neoplasms, and leukaemia. Moreover, cetaceans demonstrated a 2.4% faster turnover rate of TSGs compared to other mammals. The unique molecular variants in TSGs found in baleen whales, coupled with the accelerated gene turnover rate, may have favoured the evolution of their distinctive traits: resistance to cancer, gigantism, and longevity. Furthermore, the research identified 71 genes with duplications, including 11 genes linked to longevity, senescence, cell proliferation, and metabolism. Overall, these results provide evolutionary evidence that natural selection of TSGs could be the reason why species with large body sizes and extended lifespan are resistant to many diseases. Not only does this provide new insight into the genetic basis of disease resistance but Marc Tollis, a professor at Northern Arizona University, thinks that "Since cancer is a body-size and age-related disease, the search for whale-specific changes in protein coding genes that are linked to human cancer can help target potential human cancer therapies." As well as this it is hoped that the discover of new molecular variants of TSGs could lead to the creation of new treatments for cancer and age-related diseases.

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