How do cats get their stripes?

Ever wonder how your favorite furry feline got its stripes? A new study of domestic cats has revealed which genes give felines their distinctive fur patterns and hints that the same genetics may grant wild cats, such as tigers and cheetahs, their characteristic coats.   

How cats get their stripes is a decades-old mystery in the life sciences, senior author Dr. Gregory Barsh, a geneticist at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, told Live Science in an email. About 70 years ago, scientists began developing theories as to why and how organisms come to bear periodic patterns, like the stripes on a zebra or the squidgy segments of a caterpillar's body. 

In some animals, like the zebrafish, these patterns emerge due to the arrangement of different types of cells. "But in mammals, the skin and hair cells are exactly the same across the entire body, and the color pattern comes about because of differences in genetic activity between, say, cells underlying a dark stripe and cells underlying a light stripe," Barsh said. So the question of how cats get their stripes comes down to how and when various genes switch on in their cells and how those genes influence the animals' development. In short, it's complicated.

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But now, in a new study, published Tuesday (Sept. 7) in the journal Nature Communications, Barsh and his colleagues identified several genes that work together to give cats their coat patterns. 

One gene, called Transmembrane aminopeptidase Q (Taqpep), they'd identified previously, in a study published in 2012 in the journal Science. Cats that carry one version of the Taqpep gene end up decked out in dark, narrow stripes, while those with a mutant version of the gene bear "large whorls" of dark fur; the "whorl" version of the gene is most common in feral cats. 

To investigate what additional genes might shape the diverse markings on cats' coats, the team began collecting discarded tissue from clinics that spay feral cats; some of the resected cat uteruses contained non-viable embryos, which the researchers examined in the lab.

They noticed that, at about 28 to 30 days old, cat embryos develop regions of "thick" and "thin" skin; at later stages of development, the thick and thin skin gives rise to hair follicles that produce different types of melanin — eumelanin for dark fur, and pheomelanin for light fur. 

Remarkably, "the developmental mechanism responsible for color pattern takes place early in development, before hair follicles are formed and within cells that do not actually make any pigment but instead contribute to hair follicle structure," Barsh said. Spotting this pattern, the team examined which genes were active leading up to the development of the thick skin, to see if specific genes directed the patterns' formation.

The team found that, in 20-day-old embryos, several genes involved in cell growth and development suddenly switch on in the skin later destined to thicken and give rise to dark-fur-producing follicles. These genes are known to be involved in a "Wnt signaling pathway," a molecular chain reaction that drives cells to grow and develop into specific cell types, and one gene in particular, called Dkk4, stood out as particularly active.

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Dkk4 codes for a protein that turns down Wnt signalling, and when it comes to cat fur, the tug-of-war between Dkk4 and Wnt seems to dictate whether a patch of fur ends up dark or light, the authors found. In the dark patches, Dkk4 and Wnt balance each other out, but in the light patches, Dkk4 beats out the Wnt.   

This finding supports a theory that computing pioneer Alan Turing developed in the 1950s, Science magazine reported. Turing proposed that animals' periodic patterns, like stripes, crop up when an "activator" molecule boosts the production of an "inhibitor" molecule, and these two molecules mingle in the same tissue; in this case, Wnt would be the activator and Dkk4 the inhibitor. Following Turing's hypothesis, Barsh's team thinks that Dkk4 spreads through tissue more quickly than the Wnt signalling travels, and that this uneven distribution generates periodic patches of light and dark in cats. 

What's more, a cat's Taqpep genotype — meaning whether it carries the "stripe" or "whorl" version of the gene — also dictates where the Dkk4 gene can be activated, Barsh said. "But we don't know exactly how that happens," he added. Taqpep codes for a protease, an enzyme that breaks down other proteins, but for now, the team doesn't know whether this enzyme affects Dkk4 activity directly or indirectly.

As a follow-up to the embryo analyses, the team examined cat genome sequences from a database called the 99 Lives collection. They found that Abyssinian and Singapura breeds, which bear no stripes or spots and instead have a uniform appearance, carry mutant versions of Dkk4 that disable the gene. In future work, the team wants to see whether similar mutations crop up in wild cats. 

Previous studies suggested that for cheetahs (Acinonyx jubatus), at least, a cat's Taqpep genotype affects the appearance of its spots, and the same might go for Dkk4, the authors noted. Then there's the serval (Felis serval), an African wild cat that usually sports bold, black spots but occasionally grows a coat of tiny, tightly packed specks instead. Could a Dkk4 mutation explain this variation?  

"Our observations to date are only on domestic cats," Barsh said. "It is quite likely that the molecules and mechanisms studied in domestic cats apply to all of the more than 30 species of wild cats, but we will need to carry out additional studies of wild cat DNA to know that for sure." 

Beyond wild cats, the team wants to study whether the same mechanisms are also at play in distantly related mammals, such as zebras and giraffes. 

Originally published on Live Science.