HudsonAlpha, HHMI and Harvard researchers discover molecular mechanism that cause stripes on mice

According to one Native American legend, Chipmunk got his stripes after teasing Bear mercilessly. In retaliation, the large predator pinned the tiny mammal under his paw. Chipmunk begged Bear to lift his paw just enough for breath and escaped when Bear eased his weight just a little. As Chipmunk ran back home, Bear’s large claws swiped his back, and the animal was left with stripes on his back that his descendants carry to this day.

While the legend creates an interesting story – and imparts a moral lesson – a team of researchers from the HudsonAlpha Institute for Biotechnology, Howard Hughes Medical Institute (HHMI) and Harvard University have discovered the real molecular cause of the color pattern on chipmunks and striped mice in a project whose results are published online in Nature. The work at HudsonAlpha was led by Corneliu Henegar, MD, PhD, a senior scientist in the research group of faculty member Greg Barsh, MD, PhD.

“Using African striped mice, we have identified a new mechanism to produce pigment patterning,” Hopi Hoekstra, PhD, and Ricardo Mallarino, PhD, wrote on the Harvard University Department of Molecular and Cellular Biology website. “Thus, we advance our understanding of the formation and evolution of the remarkable array of mammalian coat color patterns found in nature, and gain insights into the molecular and cellular mechanisms by which phenotypic variation originates.” HHMI Investigator Hoekstra, of Harvard University, led the striped mice project. Ricardo Mallarino, a postdoctoral fellow in Hoekstra’s lab, is the lead author of the Nature paper.

An animal’s coat color or pattern, like stripes on a chipmunk or spots on a leopard, can influence how well a critter fits into its environment, avoids predators and even communicates with potential mates or competitors. How those color patterns evolved and what molecular mechanisms in the animal’s DNA causes them has remained a mystery, however. This project helped identify the molecular pathways that cause the hair color patterns. Remarkably, the same pathway has arisen independently in two distantly related species.

The team started their project with Rhabdomys pumilio, also known as the four-striped mouse. Like its distant cousin the house mouse, the animals can be studied in the laboratory. Mallarino discovered that the stripes in these animals arose from differences in maturation of melanocytes, the cells in the skin that form pigment. The team realized that those differences arose due to the action of a molecule called Alx3, expressed in light stripes but not dark stripes, and that acts to inhibit melanocyte maturation.

Chipmunk stripes look just like those on four-striped mice, even though the two animals are no more closely related than cats and dogs. And, remarkably, the researchers found that the same molecular mechanism has been used in both species, with elevated levels of Alx3 in light stripes of chipmunks as well as mice. The results reveal a new mechanism for evolutionary novelty, and provide new insight into an unsolved mystery in biology.

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