The Role of TP53 in Adaptation and Evolution

The TP53 gene is a major player in cancer formation, and it is considered the most important tumor suppressor gene. The p53 protein acts as a transcription factor, and it is involved in DNA repair, senescence, cell-cycle control, autophagy, and apoptosis. Beyond cancer, there is evidence that TP53 is associated with fertility, aging, and longevity. Additionally, more evidence exists that genetic variants in TP53 are associated with environmental adaptation. Special TP53 amino-acid residues or pathogenic TP53 mutations seem to be adaptive for animals living in hypoxic and cold environments or having been exposed to starvation, respectively. At the somatic level, it has recently been proven that multiple cancer genes, including TP53, are under positive selection in healthy human tissues. It is not clear why these driver mutations do not transform these tissues into cancerous ones. Other studies have shown that elephants have multiple TP53 copies, probably this being the reason for the very low cancer incidence in these large animals. This may explain the famous Peto's paradox. This review discusses in detail the multilevel role of TP53 in adaptation, according to the published evidence. This role is complicated, and it extends from cells to individuals and to populations.

Automated summary

The TP53 gene is crucial in cancer formation and is considered the most important tumor suppressor gene. It functions as a transcription factor and is involved in various cellular processes. TP53 is also associated with fertility, aging, longevity, and environmental adaptation. Studies have shown that TP53 mutations are beneficial for animals living in specific environments, and multiple copies of TP53 in elephants may explain their low cancer incidence. This review provides an in-depth analysis of TP53's role in adaptation across different levels.