What makes a Dun horse pale?

HudsonAlpha scientists part of team to discover gene for horse coloration

Huntsville, Ala. – While the gleaming coat of a sleek chestnut quarter horse may be eye-catching, its ancestor’s paler hair and zebra-like markings, known as the Dun pattern, helped it blend into its surroundings. Now an international team of scientists has pinpointed the genetic basis of that ancestral wild-type pattern.

The team’s results, published online today in Nature Genetics, reveal a new mechanism of skin and hair biology and provide new insight into horse domestication.

“We have many examples in biology where you see repetitive structures like vertebrae or ridges on fingertips,” said Greg Barsh, MD, PhD, a faculty investigator at the HudsonAlpha Institute for Biotechnology. “For the most part,” he added, “we know very little about the genes, signals and pathways in biology that set those things up. We want to know how patterns in biology come about, so we’re looking at the Dun pattern to learn more.”

Barsh’s research group worked with a team led by Leif Andersson, PhD, at Uppsala University in Sweden for the project. Freya Imsland, PhD, from Andersson’s group and Kelly McGowan, MD, PhD, from Barsh’s group, are co-lead authors on the study.

“Dun is clearly one of the most interesting coat color variants in domestic animals because it does not just change the color but the color pattern,” said Andersson. “We were really curious to understand the underlying molecular mechanism for why Dun pigment dilution did not affect all parts of the body.”

For horses, the Dun pattern is typified by pale coat coloring on most of the body. The pattern also includes barring on the legs similar to zebra stripes, a darker forehead, a strip of dark hair down the middle of the back called a dorsal stripe, and dark eye rims that look like thick eye liner. The combined coloration provides camouflage in the wild.

To uncover the mechanism behind the Dun pattern, the team first examined the distribution of pigment in individual hairs. In the darker parts of the Dun horse – on those zebra-like stripes, for example – pigment is spread throughout the hair. But in the lighter areas the pigment only saturates half of the hair, making one side of the hair intensely colored with the other side much lighter. When the hair grows out, it curves over. The darker, pigmented half of the hair lies on top with the paler half underneath.

The team’s genetic analysis and DNA sequencing revealed that Dun versus non-dun color is determined by a single gene that codes for the T-box 3 (TBX3) transcription factor. Transcription factors are proteins that allow for unique expression of genes in different cell types and during development. In humans, inactivating the TBX3 gene causes a constellation of birth defects known as Ulnar-Mammary Syndrome. But in horses that have lost their Dun color, TBX3 changes only affect where the gene is expressed in a growing hair.

“Previous studies in humans and laboratory mice show that TBX3 controls several critical processes in development that affect bones, breast tissue and cardiac conduction,” said Barsh, whose group led the tissue analysis. “We were surprised to find that TBX3 also plays a critical role in skin and hair development.”

The team wanted to know exactly how TBX3 affects hair color in horses. So the group measured how TBX3 is distributed in individual hairs and compared that distribution to other molecules that regulate pigmentation. And they found a match with melanocytes.

“In growing hairs, TBX3 mirrors the distribution of melanocytes, the cells that produce pigment,” said McGowan. “Our results suggest that TBX3 affects differentiation of specific cells in the hair, creating a microenvironment that inhibits melanocytes from living in the ‘inner’ half of the hair.”

The ancestor to all equids – zebras, horses and donkeys, for example – was Dun, but in contrast to their Dun ancestors, most domestic horses are non-dun with saturated and uniform black, brown or reddish coat coloration.

The group speculates that this new understanding of TBX3 and how it is expressed could also help to explain zebra stripes.

“What we learned here about color patterns,” Barsh said, “could be applied to other aspects of biology where there are regular patterns, like zebra stripes.”


About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to innovating in the field of genomic technology and sciences across a spectrum of biological challenges. Founded in 2008, its mission is four-fold: sparking scientific discoveries that can impact human health and well-being; bringing genomic medicine into clinical care; fostering biotech entrepreneurship; and encouraging the creation of a genomics-literate workforce and society. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. Designed to be a hothouse of biotech economic development, HudsonAlpha’s state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. The relationships formed on the HudsonAlpha campus encourage collaborations that produce advances in medicine and agriculture. Under the leadership of Dr. Richard M. Myers, a key collaborator on the Human Genome Project, HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education, and includes 29 diverse biotech companies on campus. To learn more about HudsonAlpha, visit: