Genetic Mutation Fuels Horse Endurance: KEAP1 Gene Adaptation Unveiled

Horses' exceptional athletic abilities, particularly their speed and endurance, stem from a genetic mutation in the KEAP1 gene. This mutation, detailed in *Science*, enhances energy production and protects against cellular oxidative stress. Researchers from U.S. universities discovered that modern horses, donkeys, and zebras possess a 'stop codon' in their KEAP1 gene, which shortens the DNA message. This adaptation improves the gene's functionality, preventing the reduction of the NRF2 protein, crucial for mitigating oxidative stress. The result is increased mitochondrial energy and quicker physical recovery. The study, involving an evolutionary analysis of the KEAP1 gene across 196 mammal species, suggests this genetic adaptation is key to horses' endurance. Scientists initially believed the mutation created a shorter, nonfunctional KEAP1 protein, but later found it increased sensitivity to cellular stress by adding another interaction point for reactive oxygen species (ROS). This allows horse cells to respond faster to the stress of intense exercise. This finding may offer insights for treating human diseases related to inflammation and aging.