Orange Cats Came Before the Color Orange?

Ever since humans domesticated cats over 10,000 years ago, humans have developed a kinship with the furry felines, especially unique orange cats. However, it’s not just human domestication and obsession with animal aesthetics that has allowed orange fur to persist since at least the 12th century—the preservation of orange fur can also be attributed to a deletion of a gene in the X chromosome.

For decades, scientists were bewildered by the genetics surrounding the orange fur of a cat because they could not locate the specific gene responsible for orange fur. Genes are units of heredity that are building blocks for chromosomes. Genes instruct your body to make certain proteins to carry out bodily functions, and some genes even help control other genes. Zooming into DNA even more, there are base pairs, which are pairs of complementary DNA nucleotide bases that help build the rungs of the DNA ladder. The base adenine pairs with thymine, and cytosine pairs with guanine. 

But they knew that orange fur was X-linked because male cats (with XY chromosomes) almost always had orange fur. This suggested to scientists that in order to have orange fur, a cat only needed the genetic mutation on one X chromosome. 

However, two separate research teams from Stanford and Kyushu University concurrently concluded that the deletion of 5,074 base pairs in the ARHGAP36 gene—a gene previously associated with pigmentation—is the true reason for orange fur in cats. The researchers from Kyushu University sequenced DNA from 18 cats (such as orange, calico, and non-orange cats). They identified variants in the orange cats’ genomes and narrowed them down until one candidate was consistently found in only orange cats and absent in the non-orange cat group. 

The Stanford team, on the other hand, identified an interval on the X chromosome containing a haplotype, a set of DNA variants that tend to be inherited together, shared by all orange cats. Although most of these variants appeared in non-orange fur cats too, there were three unique to orange cats, including the deletions in the ARHGAP36 gene. The deletions in the gene were the strongest candidate for orange fur because they superbly correlated with orange fur in 188 cats and led to increased expression of the pigmentation gene ARHGAP36.

Rather than producing brown-black fur, these deletions cause pigment cells to produce a yellow-red color. The ARHGAP36 gene also manifests as patches of orange that make the cat appear “calico” or “tortoiseshell.” Female cats need both X chromosomes to have the gene mutation be uniformly orange. If one X chromosome has this mutation, female cats have these calico or tortoiseshell patterns.

Considering that humans tend to perceive orange cats to be more friendly and that these variants have not been found in other animals including wild cats, perhaps this gives some explanation as to why orange fur is unique to domesticated cats and suggests that human artificial selection may have played a role in the persistence of this orange fur to this day. 

In addition to their unique physical differences, orange cats are more common and enjoy greater reproductive success in rural areas. Scientists have observed that the mating system of cats in a rural area involves a male cat mating with multiple females and a female cat mating with only one male. This results in an increase in the frequency of the orange fur gene because males can easily pass the orange fur gene to have male offspring with fully orange fur or female offspring with orange fur. 

Another factor that increases the reproductive success of orange cats is that males tend to weigh more than cats of other colors, while orange females weigh less. There has been a documented correlation between size (including weight) and aggression towards other cats. This increased sexual dimorphism, or observable differences in the appearances of the sexes of a species, is advantageous because male orange cats are likely more aggressive and thus may enjoy greater reproductive success.

Orange cats are not just empty-headed creatures being princesses carried through life, as social media seems to suggest. They are persistent and possibly aggressive to other cats, but are perceived as friendly by humans. For too long, their true selves have been hidden behind mysterious orange fur and carousels on Instagram, grossly misrepresenting them. Now, when you look at your best friend’s orange cat prancing around, know that they survived like us in part because of a single deletion to their gene, and were here longer than the color orange was a word.