How cats and cheetahs get stripes and spots

September 20, 2012 § Leave a comment

A mutation in Taqpep converts a “mackerel tabby” pattern (upper) to a “blotched tabby” pattern (lower). Image courtesy of Helmi Flick.

Surely you didn’t expect a cat owner like me to pass up on a paper about kitty coat-and-color patterns? A paper in the latest issue of Science describes the genetic underpinnings of how domestic tabbies and cheetahs have mutations in a set of shared genes that give the animals their distinctive markings.

Tabby patterns come in two forms. One is mackerel, with dark, narrow stripes (I have two of these specimens). The other is blotched, with dark whorls that are less organized. Periodic color patterns in other wild and domestic cats may be a product of the same process. For instance, cheetah spots also come in two forms: in a regular dotted fashion or something similar to the blotched tabby patterns. Cheetahs with the blotched pattern are called king cheetahs.

The Barsh laboratory at the HudsonAlpha Institute for Biotechnology has a longstanding interest in studying mammalian color variation, using it as a tool to better understand basic aspects of cell signaling and gene regulation. “Cheetah spots and tabby stripes are an unsolved mystery that has led to a great deal of speculation about the underlying mechanism,” says Gregory Barsh. “Our interest was motivated by the attempt to define a molecular component of periodic patterns using genetics as a tool.”

Earlier work had shown that two different genes were involved in color-pattern formation in cats, but the identities of the genes were unknown. To figure that out, the Barsh group along with the group of Marilyn Menotti-Raymond at the National Cancer Institute, searched single nucleotide polymorphisms in 16 blotched and 33 mackerel tabby cats. The cats were feral ones held at a northern California spay/neuter clinic. “No cats were harmed during the study,” Barsh assures us.

From their analyses, the investigators concluded that a gene called Taqpep is responsible for the distinctive markings. Mutations on Taqpep caused the blotched tabby pattern.

Taqpep encodes a protease normally located in the cell membrane. But it also can be cleaved, which lets it diffuse into the extracellular matrix and interact with other molecules. This ability to freely interact with other molecules is an important aspect of the reaction diffusion principle, which explains how periodic patterns can rise out of random events.

Kgosi is a king cheetah from South Africa. Image courtesy of Steve Flaherty, Wild Cat Education and Conservation Fund.

The researchers next decided to see if Taqpep also played a similar role in cheetahs. They got hold of blood samples from a king cheetah named Kgosi, who lives in an wildcat conservation facility in northern California. They found that Kgosi also had a mutation in Taqpep. They extended the analysis to more cheetahs and confirmed a Taqpep mutation caused the king cheetah pattern.

Obviously, other animals have stripes and spots. But the nonmammals, like salamanders and fish, can add stripes and spots as they grow. But growing mammals keep the same number and pattern of their stripes and spots but just increase the surface area of contrasting colors.

“Somehow, cells in the black stripes know they are in a black stripe and remember that fact throughout the organism’s life,”  Barsh said in a press release. “We were curious about what’s happening at the boundary between light and dark stripes and spots. How do these spots know to grow with an animal?”

So the investigators next studied fetal cat skin after seven weeks of gestation and found that the tabby pattern begins to show only when the fur begins to grow. That indicated that the changes in color were caused by changes in gene expression within certain cells.

By drilling down further, the investigators established that the expression of the Edn3 gene regulated hair color. Edn3 mRNA was found at the base of the follicles making the black hairs.

“This is very strong evidence that Edn3 is a critical regulator of black versus yellow hair in animals,” said Barsh in the press release. The researchers suggest that Taqpep establishes a pattern of stripes or spots in early feline development and then Edn3 maintains the pattern as the fur grows.

Barsh says the team’s work defines the molecular mechanism responsible for sustaining periodic patterns and suggests that tiger stripes, cheetah spots and leopard rosettes have the same underlying genetic mechanism. “This work makes an important start in understanding a basic principle of biology — how periodic patterns in nature are established and maintained,” he says.

My two mackerel tabbies.

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