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Horses are exceptional athletes, able to push their large bodies further and faster than just about any other animal. A new study in the journal Science suggests that an unusual genetic change might be behind that athleticism. NPR's Jonathan Lambert has more.
JONATHAN LAMBERT, BYLINE: To run far and fast, cells need a lot of energy. But the process cells use to produce that energy has a cost, explains Vanderbilt University biologist, Gianni Castiglione.
GIANNI CASTIGLIONE: You know, to make energy, we've made a deal with the devil to basically have a slow-burning fire in our cells.
LAMBERT: That fire essentially burns oxygen to make energy, but that creates a lot of smoke, or oxidative stress, that can cause cellular damage. Antioxidants can mitigate this damage, and animals regulate this balance through a key gene pathway called NRFP-KEAP1 (ph).
CASTIGLIONE: To not get burned, you need this NRF2 system. This is essentially the energy production and fire department all wrapped in one of the cell.
LAMBERT: Castiglione and his colleagues wanted to see if any animals had evolved workarounds to this trade-off. They scanned the genomes of nearly 200 mammalian species looking for unusual variants to this system. Horses stood out with a single, strange mutation.
CASTIGLIONE: This is a type of mutation called a nonsense mutation. And that's because what it does is inactivates a gene from doing what the cell needs it to do.
LAMBERT: It does that by essentially inserting a stop sign, called a stop codon, in the middle of that key gene instead of just at the end. This mutation kills mice, probably because it allows too much smoke to build up in cells. So Castiglione was stumped.
CASTIGLIONE: We have to dig really deep and try to figure out what exactly is going on here.
LAMBERT: Through a variety of genetic and molecular techniques, Castiglione and his colleagues discovered that horses evolved a way to go around that extra stop sign.
CASTIGLIONE: We found that horses have somehow come up with a back door, so to speak, where they've changed the interpretation of the genetic code, so it doesn't mean break this protein; it means do something different.
LAMBERT: That something - which they still don't fully understand - allows horse cells to produce up to five times more energy than mouse cells, while simultaneously ramping up their damage control system by 200%. This combination of mutations allows their muscle cells to basically run hotter than other animals, says Elia Duh, a study coauthor and researcher at Johns Hopkins University.
ELIA DUH: This provides them with the biochemical means to run fast and over long distances. They've ascended into the pantheon of the greatest athletes among animals.
LAMBERT: Samantha Brooks, a genetics researcher at the University of Florida, agrees that these mutations helped horses become aerobic powerhouses. And to her, the paper also shows just how weird evolution can be.
SAMANTHA BROOKS: Stop codons are generally, in genetics, considered to be bad news, and it really should have caused a catastrophic loss of function for this protein. But instead, the ancestors here of these species somehow managed to really turn that lemon into lemonade.
LAMBERT: This adaptation in horses could have implications for human health. Many inherited diseases, like cystic fibrosis and muscular dystrophy, stem from stop codons arising in important genes. The researchers hope that understanding how horses evolved workarounds might inspire new treatments in humans. Jonathan Lambert NPR News.
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