an orange cat sitting on a shelf

The genetic basis for the coloration of orange cats has long been unknown to scientists.

oxygen via Getty Images


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


Now two independent studies of American And Japanese Scientists investigated the genetic origins of these cats’ color, and separately the teams came to the same conclusion. They suggest that orange cats have their bright, warm coats due to genetic variations on their X chromosomes. The articles, which have not yet been peer-reviewed, were recently posted to the preprint server bioRxiv.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 the genome of cats to determine which protein encoded by a cat’s genes brought out the orange hue. What they discovered was astonishing: a small deletion in the cat’s DNA affected the entire color scheme.


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


In most other mammals, mutations in a protein called Mc1r lead to red hair color. But this has not explained the orange color patterns in cats. “It was a genetic mystery, a riddle,” says Barsh Science‘s Sara Reardon.


Instead, the new studies point to a gene called Arhgap36, a protein on the X chromosome. It was never on the list of potential candidates for the ‘orange gene’, so to speak, because it controls aspects of embryonic development. As a result, scientists thought that large mutations in Arhgap36 would likely kill the animal, Barsh said.


Still, Barsh’s team found that Arhgap36 in orange cats produced nearly 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 looked closer, they saw that increased levels of Arhgap36 in melanocytes, or skin cells that produce hair color, led to the production of a light red pigment, which makes a cat’s coat appear orange.


But the change was not due to a dangerous mutation. Rather, a small portion of DNA was missing, meaning the unusual amount of Arhgap36 could not affect anything other than the melanocytes. Cats with the orange variant are ‘not only healthy, but also cute’ Science writes.



an orange cat looks into the camera


The new research adds evidence to support that the orange trait is sex-linked, as most ginger cats are males.


Karen Warren/Houston Chronicle/Hearst Newspapers via Getty Images



Because Arhgap36 is located on the X chromosome, the orange color is sex-linked, researchers suggest. That makes sense, because completely red cats are usually males. The new findings also help explain why calicoes and tortoiseshells – which are patterned with a mixture of colors, including orange – are almost always female.


This is because a male kitten inherits only one X chromosome from his mother, while female kittens inherit an X chromosome from each parent. So a female cat is less likely to receive two copies of the Arhgap36 variant that produces orange color. However, in a male cat, the cat only needs 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 they want to express or reveal on different parts of the cat’s coat. The chromosome that isn’t chosen is “inactivated,” and the randomness of this process gives turtles their distinctive pattern. Calico cats also have white spots.



a tortoiseshell cat sits in front of a toy mouse


Tortoiseshell cats, characterized by a mottled pattern of orange and black, are usually female.


Flore Y via Getty Images



Although the findings still need to undergo peer review, scientists are excited about the new work. “This means that a new route for pigment production has been discovered,” geneticists write Frank Nicholas, Imke Tammen And Leslie A. Lyon for the Conversation. This “opens the way for exciting and important research into a fundamental biological process,” added the three researchers, who were not involved in the work.


“I am completely convinced that this is the gene and I am happy,” Carolyn Brownsays a geneticist at the University of British Columbia in Canada who was not involved in either study Science. “It’s a question I always wanted an 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 neighboring cells,” Christopher Kaelinsays geneticist at Stanford University and co-author of the American study Newsweek.


Sasaki, from the Japanese study, is excited about what could happen 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 worldwide in orange-colored cats.”




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