For more than a century, the genetic secrets behind the vibrant orange coats of ginger cats and the intricate patterns of tortoiseshells have puzzled scientists and cat enthusiasts alike.

Now, two studies have finally identified the genetic key to this mystery, solving a puzzle first theorized in 1912. The studies, conducted independently by Japanese and American research teams, have pinpointed the gene responsible for orange coat coloration in cats: ARHGAP36, informally dubbed the "Orange" gene.

This discovery not only confirms a 110-year-old hypothesis, but also sheds light on a new biological pathway involved in pigmentation.

In 1912, American geneticist Clarence Cook Little proposed a visionary idea linking coat color inheritance in cats to the X chromosome.

His theory suggested that orange coat color was controlled by a variant on the X chromosome, explaining why ginger cats are mostly male and why tortoiseshell cats, with their mix of orange and non-orange fur, are almost always female.

Little's hypothesis predicted that males, having only one X chromosome (XY), could only be fully orange or non-orange, while females (XX) could inherit one of each variant, resulting in the tortoiseshell pattern.

He also calculated that ginger females, needing two orange variants, would be relatively rare.

"Tortoiseshell and calico males do sometimes occur, but it's usually due to an abnormality of the number of sex chromosomes, such as one too many X chromosomes (XXY), which also causes sterility," scientists from University of Sydney and University of Missouri in Columbia recently wrote in an article about the findings published in The Conversation.

Fast forward to today, researchers have identified ARHGAP36 as the Orange gene.

A deletion mutation in this gene, they found, affects how its associated protein operates during hair follicle development. In orange areas of a cat's coat, the gene remains persistently active, while in non-orange areas, it is largely switched off.

This mutation, while not altering the protein itself, disrupts its location of activity, resulting in the distinctive orange pigmentation.

Newsweek contacted authors of both studies via email for comment.

Orange cats have been around for millennia. Evidence of ginger cats can be seen in Egyptian tomb art, and some mummified cats appear to have had ginger coats.

Despite their ubiquity in pop culture today—from Garfield to Harry Potter—orange remains one of the rarer coat colors in the feline world.

The identification of the Orange gene not only confirms Little's predictions, but also reveals an entirely new pathway in pigment biology.

ARHGAP36 was previously known for its role in hair follicle development, but its involvement in pigmentation was a new finding.

"Even though much remains to be discovered, ginger cats and their owners around the world can rejoice—the genetic basis of their distinctive coat colour has finally been worked out, more than 110 years after it was first proposed," the scientists wrote.

Both studies are yet to be peer-reviewed and are available on the pre-print server bioRxiv.

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References

Kaelin, C. B., McGowan, K. A., Trotman, J. C., Koroma, D. C., David, V. A., Menotti-Raymond, M., Graff, E. C., Schmidt-Küntzel, A., Oancea, E., & Barsh, G. S. (2024). Molecular and genetic characterization of sex-linked orange coat color in the domestic cat (p. 2024.11.21.624608). bioRxiv. https://doi.org/10.1101/2024.11.21.624608

Toh, H., Yeung, W. K. A., Unoki, M., Matsumoto, Y., Miki, Y., Matsumura, Y., Baba, Y., Sado, T., Nakamura, Y., Matsuda, M., & Sasaki, H. (2024). A deletion at the X-linked ARHGAP36 gene locus is associated with the orange coloration of tortoiseshell and calico cats (p. 2024.11.19.624036). bioRxiv. https://doi.org/10.1101/2024.11.19.624036