Elephant genes may hold clues for cancer prevention. Scientists from seven UK institutions, including scholars from Oxford and Edinburgh, are using innovative bioinformatics models to explore molecular interactions. The p53 protein is known to guard against cancer.
The study, published in Molecular Biology and Evolution, offers fresh insights into evolution and the molecular interactions that could lower cancer risk in people. Elephants have much to tell us about this issue.
When a body functions well, cells routinely replicate: old cells are replaced by new ones, each carrying exact copies of genetic material.
If proteins copy DNA incorrectly, mutations arise. This happens often, but cells repair most errors; the rate and quality of repair depend on genetics and external conditions.
Exposure to toxins, stress, aging, and poor living conditions can raise mutation rates and, with them, the likelihood of tumors.
The accumulation of genetic mutations raises cancer risk with age. Yet elephants do not follow this pattern.
Despite their large size and long lifespans similar to humans, cancer mortality in elephants is estimated to be under 5 percent, compared with about 25 percent in humans.
Researchers point to more copies of the p53 gene in elephants—around 20 copies, each a slightly different version—as a genome protection advantage over species with a single copy.
A protein key in the fight against tumors
Professor Fritz Vollrath, affiliated with the University of Oxford, Save the Elephants and a co-author of the study, remarked on the significance of the findings: this work highlights the remarkable biology of elephants and the need to study these animals closely. Their genetics and physiology are shaped by ecology, diet, behavior, and evolutionary history.
A female elephant helps her calf cross the river. (image credits: pixabay)
The p53 protein plays a crucial role in regulating DNA repair and in suppressing uncontrolled cell growth.
p53 activates when DNA is damaged and helps halt replication, allowing repair of copies that are incorrect. In cells with intact DNA, p53 activity is not constantly needed and is kept in check by other proteins, including MDM2, an oncogene that can tag p53 for degradation.
The interaction between p53 and MDM2 is essential for the multiplication of healthy cells, repair of damaged cells, and the removal of cells with severe damage or unrepaired errors.
Elephants may appear genetically gifted with multiple p53 alleles, but each allele has its own subtle structure. This diversity may give elephants a broader set of molecular tools to counter cancer than humans, who typically carry two copies of a single gene.
Biochemical analyses and computer simulations reveal key differences in how various p53 isoforms interact with MDM2.
An exciting breakthrough
Small variations in the p53 sequence create distinct molecular shapes that significantly alter how p53 binds MDM2. In some cases, p53 remains active longer, continuing the fight against mutations.
Unlike humans, certain elephant p53 isoforms are not degraded or inactivated by MDM2. This may be a reason why these giants experience lower cancer rates, a hypothesis supported by researchers.
A few elephants in the Cabárceno nature park in Cantabria are pictured as a reminder of the study’s subject. (image credits: Ramon Diaz)
Professor Robin Fåhraeus, a co-author, called the findings an exciting step forward in understanding how p53 contributes to cancer prevention. In humans, p53 helps decide whether cells should halt growth or undergo programmed cell death, but the full mechanism was long hard to pin down.
Fåhraeus noted that multiple elephant p53 isoforms, with diverse interactions with MDM2, open new avenues for research into tumor suppression.
Konstantinos Karakostis, the study’s lead author, explained that clusters of altered p53 variants may collectively regulate cellular responses to various stresses, offering a model with high potential for biomedical applications.
The next step is to deepen the understanding of how p53 molecules are activated and when this enhances sensitivity to cancer conditions. The aim is to guide the development of targeted therapies to prevent and treat cancer in humans.
Reference work: a scholarly article in Molecular Biology and Evolution, volume 39, issue 7, msac149, 6632613. (Citation: Breadth and depth of p53 research in elephants.)