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Large animals and deadly diseases

25.10.2015

Cancer affects not only humans but also animals. But everything is different - someone more often, someone less often. There are species that are especially resistant to cancer, and these, oddly enough, include the largest mammals: elephants and whales. Why "oddly enough"? We know that cancer starts with cells that have lost control of division. Obviously, the more cells in the body, the greater the chance that something will go wrong in one of them - during division, for example, an error can creep into the synthesized DNA chain. However, elephants, despite their size and long lifespan, get cancer even less often than smaller species. This paradox has been called the Peto paradox, after Richard Peto, a British epidemiologist at Oxford who noticed it back in the 1970s.

Obviously, long-lived large animals have some additional mechanisms that suppress the occurrence of malignant tumors. Among the genes on which the development of cancer depends, there are proto-oncogenes and anti-oncogenes. If the first ones start to work not as they should, the cells "go crazy" and become cancerous; accordingly, the same will happen if the anti-oncogenes that monitor whether the cells behave correctly are broken.

Two years ago, researchers at the Institute for Development in Montpellier proposed a model that took into account the behavior of proto-oncogenes and anti-oncogenes depending on the size of the animal. The model simulated different distributions of mutations over several thousand generations. The conclusion turned out to be this: proto-oncogenes and anti-oncogenes react differently in evolution to an increase in body weight. The greater the body weight, the more difficult it is to activate the genes that can provoke a tumor.

One of the mutations that makes it more difficult to activate proto-oncogenes may be due to the fact that the number of tumor suppressors in the genome simply increases. Joshua D. Schiffman of the University of Utah and colleagues from the University of Arizona and the University of Pennsylvania write about this in their article in the Journal of the American Medical Association. First, the authors of the work analyzed the mortality statistics of elephants, and again once again made sure that they are really resistant to cancer more than many other species: only 5% of pachyderms die from tumors, while, for example, in hyena-like dogs, cancer kills 8%, not talking about 25% of people.

Genome analysis has shown that African elephants have as many as 40 copies of the p53 gene, while Asian elephants have between 30 and 40. This gene is one of the best known anti-oncogenes. The p53 protein recognizes damage in DNA, and if there are enough of them, it turns on the genes responsible for apoptosis - programmed cell suicide. A large amount of genetic damage makes the cell dangerous for the whole organism, so the easiest way is to get rid of it altogether. Obviously, it is the huge number of copies of p53 that arose in their genome millions of years ago that helps elephants avoid cancer (humans, by the way, have only two copies of p53).

You can, of course, do otherwise - try to repair damaged DNA, however, when elephant cells were irradiated with ionizing radiation, no activation of DNA-repair genes and proteins was observed, but the cells began to actively die. That is, the elephantine way to avoid a malignant tumor is to simply kill the spoiled cell in time. One has only to regret that evolution could not provide our genome with an extra dozen copies of p53; perhaps in the future, biotechnology will allow such an operation to be performed, and new people will be born with increased protection against cancer.

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