Have you ever wondered how horses became such powerful and enduring runners?
Scientists at Johns Hopkins Medicine believe they’ve found the answer in a surprising place—inside the genes of horses, donkeys, and zebras.
According to new research, a special genetic mutation and an unusual trick in their DNA may be the secret behind their speed and stamina.
The study, published in Science on March 27, focused on a pair of genes called NRF2 and KEAP1, which are important in how cells handle energy and stress.
These genes are found in all vertebrates, including humans.
NRF2 helps cells protect themselves from damage and supports energy production, especially when the body is under stress, like during exercise. KEAP1 acts like a sensor, detecting harmful molecules and controlling how much NRF2 is available to do its job.
In most animals, if a stop signal appears too early in the KEAP1 gene, it can shut down the production of this protein, leading to serious problems.
These early stop signs, called premature stop codons, are responsible for many inherited diseases in humans, such as cystic fibrosis and muscular dystrophy.
But horses, donkeys, and zebras seem to have evolved a way to “run through” this genetic stop sign.
The researchers discovered that in horses, there is indeed a premature stop codon in the KEAP1 gene. Normally, this would cause the gene to stop working properly.
However, horse cells have developed a way to bypass this stop signal.
They recode the stop codon so that it no longer ends protein production early. As a result, horses are still able to make full-length, fully working KEAP1 proteins.
Even more remarkable, the KEAP1 protein in horses appears to be better at detecting harmful molecules produced during intense exercise. This means that NRF2 becomes more active, helping horse cells make more energy and better protect themselves during strenuous activity.
Dr. Elia Duh, a professor at Johns Hopkins and one of the study’s authors, says this discovery may not only explain horses’ athletic power but could also help scientists find new treatments for diseases in humans.
Because the NRF2/KEAP1 pathway plays a role in aging and chronic illness, understanding how it works in horses could lead to new medical strategies.
The researchers are also hopeful that the trick horses use to bypass the stop codon might someday help doctors treat genetic diseases in people caused by similar faulty stop signals. What makes horses such amazing runners might also help unlock better treatments for human diseases.
