How have horses evolved to be so fast and powerful? (Geenee_82/Shutterstock)
In a nutshell
- A genetic mutation that should have broken a critical protein in horses instead gets cleverly “recoded,” allowing their cells to produce more energy and better resist stress during intense exercise.
- This mutation, shared by all living horses, zebras, and donkeys, likely evolved in a common ancestor around 4–4.5 million years ago and helps explain their extraordinary oxygen consumption and athletic endurance.
- The discovery challenges assumptions about how genes work in mammals and could inform new treatments for human diseases caused by similar stop codon mutations, which affect about 11% of genetic disorders.
NASHVILLE — Thoroughbred racehorses are biological marvels that consume oxygen at astonishing rates, more than double what elite human athletes can manage. During intense exercise, these animals process up to 360 liters of oxygen per minute, feeding the enormous energy needs of muscles that make up over half their body weight.
For years, researchers have wondered how horses evolved this exceptional capacity. The fossil record tells us they started as dog-sized leaf browsers before transforming into the powerful runners we know today. But the molecular changes that enabled this transformation remained hidden, until now.
The Genetic Puzzle of Horse Power
A team of researchers from Vanderbilt and Johns Hopkins recently uncovered a fascinating evolutionary twist that helps explain horses’ metabolic superpower. In work published in Science, they found what initially looked like a genetic error that should have been harmful but instead became an advantage through clever biological trickery that boosts energy production.
The researchers examined a system that controls how cells handle stress from burning oxygen. This system becomes especially important during exercise. It involves two main players: a protein called KEAP1 that acts as a sensor for stress, and another called NRF2 that turns on protective genes when needed.
When looking at the KEAP1 gene in horses, zebras, and donkeys, the scientists spotted an odd genetic “stop sign” early in the gene’s instructions. Normally, this kind of mutation would prematurely end protein production, creating shortened, non-working proteins that cause disease.
Yet these animals not only survive with what should be a harmful mutation, they excel as some of nature’s greatest athletes. This contradiction made the researchers dig deeper.
Reading Through the Stop Sign
In horses and their relatives, this genetic stop sign isn’t actually stopping anything. Instead, the cellular machinery ignores it and keeps reading, inserting a different building block (amino acid) than was originally there.
The modified KEAP1 becomes more responsive to stresses from burning oxygen, leading to increased protective activity. This creates more antioxidants that shield cells from damage while also boosting energy production.
The team confirmed these effects by comparing horse and mouse muscle cells. Horse cells burned significantly more oxygen and produced more energy. When exposed to harmful compounds, horse cells also proved much more resistant to damage than cells from other species.
To test whether this specific mutation directly caused these effects, the researchers create
