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A horse of a different color

Dun

Long before domesticated horses showed up with their striking chestnut, bay or spotted coats, wild horses stuck to the classic look of a dun coat — typically tan all over with a dark stripe down the back, and distinctive dark markings on the shoulders, face, and ankles. (Picture the horses in the Lascaux paleolithic cave paintings of southern France.)

Now, Gregory Barsh, MD, PhD, an emeritus professor of genetics and of pediatrics, and an international team of researchers have shown how simple mutations in a single gene can turn this coat pattern on or off.

The dun gene makes a protein that binds to DNA and controls other genes, a type of protein called a transcription factor. Barsh and his colleagues showed that the dun coat transcription factor — called T-box 3, or TBX3 — makes its presence known in the tiny hair follicles that make each hair of a horse’s fur. In humans, mutations in a similar gene cause serious birth defects.

But in horses with the dun transcription factor, the hair follicle puts pigments on only one-half of the shaft of each hair. As the hair grows out and flops over, the pigment side ends up underneath, next to the body. Meanwhile, the outer surfaces of all the hairs are unpigmented with just a hint of the pigment color coming through from underneath.

The exception are the hairs in the long stripe on the back, the dark face, stripes on the hocks and shoulders — places where the hair follicles make pigment on both sides of each hair. Why remains to be seen.

Two mutations in the gene for the dun transcription factor can override the light-colored body with a dark stripe. According to the authors of the paper, published today in Nature Genetics, one version is older than domesticated horses; the other evolved in domestic horses much more recently. In both cases, the altered dun gene no long suppresses pigment on one side of the hair, so horses carrying the mutated dun gene are dark all over.

In humans, mutations in the TBX3 transcription factor gene cause a collection of rare birth defects called “ulnar-mammary syndrome.” People with this syndrome may have scant to absent hair in the eyebrows and arm pits, but the most well-known effects are missing or deformed hands and feet and shortened arms and legs.

In horses, the dun transcription factor is all about pattern. The dun gene doesn’t determine if a horse is chestnut or bay, but only if it is lighter all over except for the distinctive dark marks.

Previously Dark-skinned mice lead researchers to protein linked to bone marrow failureHow the cheetah got its stripes: A genetic tale by Stanford researchers and Stanford researchers suss out cancer mutations in genome's dark spots
Photo by Freyja Imsland

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