Elephants are unexpectedly cancer-resistant considering their vast size and extended lifespans; therefore, their DNA may hold the key to preventing malignancies.
According to a press release from the University of Oxford, a group of scientists from seven different research institutions used bioinformatic modeling to investigate the molecular relationships of the p53 protein, which is known to protect the body against cancers.
According to research that was published in Molecular Biology and Evolution, the researchers described how 20 different molecules that are specific to elephants are activated for increased sensitivity and responsiveness against carcinogenic situations. If this is investigated further, it may have a wide range of effects on how people with cancer are treated.
Cancer and elephant genes
New cells and brand-new DNA copies are created each time a cell multiplies. Although these new cells should be identical clones of the older cells, mutations can occur; most of the time, the cell quickly repairs itself.
However, the number of mutations and the caliber of repairs are influenced by both hereditary and environmental factors. The rate of mutation can be accelerated by aging, stress, unhealthful living situations, and hazardous substances. When cells divide uncontrollably and invade nearby tissues, cancer occurs. As people age, the risk of developing tumors brought on by an accumulation of DNA abnormalities increases.
Elephants, on the other hand, who are renowned for their enormous proportions and life spans comparable to humans, seem to defy this trend.
Elephants appear to defy the general tendency that tumors brought on by the accumulation of gene mutations become more dangerous with age. In contrast to humans, elephants are expected to experience cancer mortality rates of less than 5% compared to humans’ up to 25%. The 20 copies of the p53 gene found in elephants, as opposed to the one seen in other mammals, are thought to be the cause of this resilience, according to researchers.
P53: “The genome’s watchdog”
In case you were unaware, p53 plays a critical role in regulating DNA repair pathways and preventing unchecked cell proliferation. The protein is activated when DNA is harmed and assists in orchestrating a reaction that stops DNA replication and corrects any erroneous copies in the cell.
In duplicated cells with unharmed DNA, p53 repair activity is not required and is blocked by another protein, the oncogene MDM2 E3 ubiquitin ligase. The elephant has twenty p53 genes and 40 alleles, each of which has a modest physical variation. This enables the elephant, with just two variants from a single gene, to have a substantially wider variety of molecular anti-cancer interactions than a human.
Through biochemical analyses and computer simulations, the researchers in the new study identified significant differences in the early contact between the elephant’s various p53 isoforms and the MDM2.
The researchers discovered that some p53 molecules avoided the interaction with MDM2 which would typically lead to deactivation due to changes in the coding sequences and structural structure. This is significant since the results are the first to show that, in contrast to humans, MDM2 does not degrade or inactivate the several p53 isoforms found in elephants. Furthermore, learning more about p53 may aid in the creation of human-tailored pharmacological therapy.
Professor Robin Fhraeus, a co-author, said, “This is an interesting advance for our understanding of how p53 contributes to avoiding cancer formation.” “The same p53 protein controls whether cells in people should enter apoptosis or stop multiplying, but it has been challenging to understand how p53 makes this choice. Elephants have several p53 isoforms, each with a unique ability to interact with MDM2. This is an interesting new opportunity to further our understanding of p53’s tumor suppressor action.”