Just as you shouldn’t judge a book by its cover, it’s unfair to judge a cat by its fur color. Yet humans seem to have a sweet spot for orange cats. Videos of their antics fill the internet, and gingers get the leading roles in TV and movies too (think: Garfield, Heathcliff, and Puss in Boots). A 2012 survey found that people are more likely to view orange cats as friendly compared to other cats. But despite their popularity, the genetic basis of their striking fur color has puzzled scientists for decades.  In humans, reddish orange hair has been linked to certain variants of the melanocortin-1 receptor (MC1R) gene. This gene controls the production of melanin, the pigment that gives hair, skin, and eyes their color, by cells called melanocytes. These cells can make one of two forms of melanin—the red/yellow pheomelanin and the black/brown eumelanin. With particular variants of the MC1R gene, melanocytes produce mostly pheomelanin, leading to red hair and fair skin. Get the Popular Science newsletter Breakthroughs, discoveries, and DIY tips sent every weekday. Email address Sign up Thank you! By signing up you agree to our Terms of Service and Privacy Policy. It would be simple to assume that the MC1R gene is also responsible for orange fur in cats—but this is not the case. Scientists noticed that most cats with multicolor coats, like calicos or tortoiseshells, are female. This led them to believe that the genes for orange and black fur are on the X chromosome. Since females have two X chromosomes, they can inherit different fur color genes from their parents, creating mixed colors. Males, with only one X chromosome, usually have fur that’s all one color, orange or black, based on the gene they get from their mother. Since the MC1R is not on the X chromosome in cats, it cannot be the gene that causes orange fur. To figure out what causes orange fur in cats, geneticist Greg Barsh and his team at Stanford University studied the DNA on the X chromosome of male orange cats. They found that all of them had a specific stretch of DNA, about 1.28 million base pairs long, that was the same. Inside this region, they identified 51 unique DNA variants that orange cats have but non-orange cats don’t have. However, 48 of these variants also appear in some breeds that don’t have orange or calico fur, so they can’t be linked to orange fur color. This allowed Barsh’s team to narrow it down to three DNA variants. Two of these were in parts of the DNA that don’t seem to affect how genes work, but the third—a deletion of about 5,000 base pairs—was located near the Arhgap36 gene. The proximity of this deletion to a working gene made it more likely to be the cause of orange fur. Barsh and his colleagues saw that all 145 orange cats they studied, as well as 6 calico and tortoiseshell cats (which also have orange patches), had the same stretch of missing DNA near the Arhgap36 gene, while 37 non-orange cats did not.  They then analyzed skin samples from orange and non-orange cat fetuses and found that the Arhgap36 gene was much more active, producing 13 times more RNA protein, in the melanocytes of orange cats compared to those of non-orange cats. So the deletion of nearby DNA must make the Arhgap36 gene more active.  But how is this gene linked to orange fur?  Further experiments showed that when Arhgap36 is more active, it weakens the effects of the MC1R gene, which normally controls melanin production, and instructs melanocytes to produce red/yellow pheomelanin instead of black/brown eumelanin, the researchers reported in a preprint posted on bioRxiv in November 2024. Surprisingly, another research group, led by developmental biologist Hiroyuki Sasaki at Kyushu University in Japan, independently discovered the same genetic characteristic associated with orange fur at the same time. They also published their findings on bioXriv. Both studies will now need to go through peer review to verify the findings. “The fact that two groups independently identified the same gene suggests that it is likely correct,” Jonathan Losos, an evolutionary biologist at Washington University in St. Louis, tells Popular Science. This finding could generate important research into when orange fur color first appeared, says Losos. “Now that we know the gene for orange, we can look for it in ancient DNA studies of cat specimens from archaeological sites.”   “More generally, we can investigate the evolutionary significance of orange color,” he adds.  Scientists have known since 1961 that the multicolor fur coats seen in calico and tortoiseshell cats is due to a phenomenon in female mammals called X chromosome inactivation, where one of the two X chromosomes in each cell is randomly inactivated. In cats carrying two different color genes, one black and one orange, X inactivation causes different colors to be expressed in different parts of the body. “We’ve known that was happening for a long time, but now that we know the actual gene, we can get a much more detailed explanation about how the variegation is actually produced,” says Losos. At minimum, this discovery likely confirms that orange cats truly have something that sets them apart from other cats. And, as Losos notes, “it’s a big breakthrough that opens the door to a lot of interesting studies.” This story is part of Popular Science’s Ask Us Anything series, where we answer your most outlandish, mind-burning questions, from the ordinary to the off-the-wall. Have something you’ve always wanted to know? Ask us. The post Why do some cats have orange fur? New hue clues in an old mystery. appeared first on Popular Science.