From the beloved Tama, Japan’s stationmaster calico cat, to Garfield, the world-famous lasagna enthusiast, orange-colored felines have long captured hearts and imaginations. But behind their distinctive coloring lies a genetic mystery—why are most orange tabbies male while calico and tortoiseshell cats are nearly always female?
Researchers from Kyushu University, Japan, have finally solved the decades-old puzzle, identifying a mutation in the X chromosome that drives orange pigmentation in domestic cats.
The groundbreaking findings not only explain the peculiar gender ratio among ginger cats but also introduce a previously unknown mechanism of coat color development in animals.
For over a century, scientists suspected that orange fur was linked to the X chromosome. Because male cats have only one X chromosome, inheriting a single copy of the “orange gene” leads to an entirely ginger coat.
The study explains how the cat got their stripes
Female cats, however, require two copies—one on each X chromosome—to be entirely orange, which makes the trait less common. Suppose a female cat inherits one orange and one black gene. In that case, patches of orange and black emerge, forming a calico or tortoiseshell pattern due to X-chromosome inactivation.
“This effect has fascinated geneticists for years,” explains Professor Hiroyuki Sasaki, the study’s lead author and a geneticist at Kyushu University. “It’s even become the textbook example of X-chromosome inactivation, yet the gene responsible remained unknown—until now.”
Sasaki’s team examined DNA samples from 67 cats, including pure orange tabbies, calicos, and non-orange cats. Their analysis pinpointed a mutation in a gene called ARHGAP36, a section of DNA previously thought to play no role in coat color. This mutation, a small deletion in a non-coding region, alters gene activity rather than changing the protein, a rare genetic mechanism for pigmentation shifts.
Surprisingly, ARHGAP36 is usually suppressed in melanocytes, the skin’s pigment-producing cells. This suppression is lifted in cats with the mutation, leading to high ARHGAP36 activity. The researchers believe this shift reduces the production of dark eumelanin while promoting the lighter pheomelanin, resulting in orange fur.
Since ARHGAP36 is also active in various body parts, including the brain and hormone-producing glands, Sasaki suspects the mutation could influence more than just coat color.
“There’s an intriguing possibility that different fur colors could be linked to personality traits,” he says. “It’s a topic cat owners debate endlessly, but now, we might have a way to study it scientifically.”
Beyond feline genetics, the discovery could provide insights into human health conditions, including skin cancer and hair pigmentation disorders. Sasaki’s next steps include using cat cell cultures to analyze ARHGAP36’s broader biological functions and investigating ancient feline DNA to trace the origins of the orange mutation.
Whether ancient Egyptian temple cats bore this fiery hue remains unknown, but scientists now have the tools to investigate feline history—one strand of ginger fur at a time.
Journal Reference:
- Hidehiro Toh, Wan Kin Au Yeung et al. A deletion at the X-linked ARHGAP36 gene locus is associated with the orange coloration of tortoiseshell and calico cats. Current Biology. DOI: 10.1016/j.cub.2025.03.075
