Geneticists Solve the Mystery of Why Some Cats Are Orange—and Why They Tend to Be Males

Orange cats have earned an online reputation for being chaotic, energetic rascals. But among scientists, they’ve long been known for something else: the enduring mystery of their distinctive coats.

Now, two independent studies by American and Japanese scientists have probed the genetic origins of these cats’ color—and, working separately, the teams reached the same conclusion. They suggest that orange cats have their bright, warm pelts as a result of genetic variations on their X chromosomes. The papers, which have not yet been peer-reviewed, were recently posted to the preprint server bioRxiv.

Scientists Greg Barsh from Stanford University and Hiroyuki Sasaki from Japan’s Kyushu University and their teams studied feline genomes to pinpoint which protein encoded by a cat’s genes brought out the orange hue. What they found was astonishing: a tiny deletion on the cat’s DNA influenced its entire color scheme.

“Our work provides an explanation for why orange cats are a genetic unicorn of sorts,” Kelly McGowan, a Stanford University geneticist who participated in the American study, says to Tom Howarth at Newsweek. The orange cat is a “fascinating exception” to the way orange-like color variants occur in many other domestic species, such as dogs, sheep, horses or rabbits, she adds.

In most other mammals, mutations in a protein called Mc1r lead to red hair color. But this has failed to explain orange color patterns in cats. “It’s been a genetic mystery, a conundrum,” Barsh tells Science’s Sara Reardon.

Instead, the new studies point to a gene called Arhgap36, a protein on the X chromosome. It had never been in the lineup of potential candidates for the “orange gene,” so to speak, because it controls aspects of embryonic development. As a result, scientists thought major mutations to Arhgap36 would likely kill the animal, Barsh said.

Nevertheless, Barsh’s team found that Arhgap36 in orange cats produced almost 13 times more RNA—molecules that help translate DNA into proteins the body can use—compared to the same gene in other types of cats. When they took a closer look, they saw that an increased amount of Arhgap36 in melanocytes, or skin cells that produce hair color, led to production of a light red pigment, making a cat’s fur appear orange.

But the change wasn’t due to a dangerous mutation. Rather, there was a small portion of DNA missing, preventing the unusual amount of Arhgap36 from affecting anything aside from the melanocytes. So, cats with the orange variation “are not only healthy, but also cute,” Science writes.

Because Arhgap36 is on the X chromosome, the orange coloration is sex-linked, researchers suggest. That makes sense, because fully ginger cats are mostly males. The new findings also help explain why calicos and tortoiseshells—which have patterns with a mixture of colors, including orange—are almost always female.

This is because a male kitten inherits just one X chromosome, from its mother, whereas female kittens inherit an X chromosome from each parent. So, it’s less likely that a female cat would receive two copies of the Arhgap36 variant that produces orange color. For a male, however, the cat only has to receive one copy of the gene.

As for tortoiseshells and calicos, they are often the offspring of a black cat and an orange cat. These kittens would have inherited one X chromosome with the “orange gene” and one without that variant, making them female. As the embryo develops, cells randomly choose which chromosome to express, or make visible, on different parts of the cat’s pelt. The chromosome that is not chosen is “inactivated,” and the randomness of this process is what gives tortoiseshells their striking pattern. Calico cats, additionally, have patches of white.

Even though the findings still have to undergo peer review, scientists are thrilled with the new work. “This means that a new pathway for pigment production has been discovered,” write geneticists Frank Nicholas, Imke Tammen and Leslie A. Lyons for the Conversation. This opens “the way for exciting and important research into a basic biological process,” add the three researchers, who were not involved with the work.

“I am fully convinced this is the gene and am happy,” Carolyn Brown, a geneticist at the University of British Columbia in Canada who was not involved in either study, tells Science. “It’s a question I’ve always wanted the answer to.”

“Studying coat color allows us to learn how cells communicate, because a pigment cell’s decision to make light or dark pigment is influenced by signals from its neighboring cells,” Christopher Kaelin, a geneticist at Stanford University and co-author of the American study, tells Newsweek.

Sasaki, from the Japanese study, is excited for what could come next. He tells Newsweek that “an obvious next question is when and where the genetic variation arose and how it spread, as our work showed that this variation is common in cats with orange coloration worldwide.”

Gayoung Lee | | READ MORE

Gayoung Lee is a science journalist from South Korea, now based in New York. Her main interest lies in exploring the unlikely connections between science and everyday life.