Garfield, the cat character from American comics, is loved worldwide. Its orange fur is almost a symbol of Garfield. It has been assumed that the orange gene exists in male cats since most orange cats are male, but this has not been clarified for nearly a century.
Finally, scientists have unraveled the secret of orange cat fur. Hiroyuki Sasaki, a professor at the Kyushu University Medical Bioengineering Institute in Japan, noted on the 16th that he discovered a "meow-tation" that creates the orange fur in cats, in an international journal, Current Biology. Gregory Barsh, a professor at the Stanford University School of Medicine in the U.S., and his research team published similar results in the same journal that day.
Professor Sasaki noted that the sex of orange-furred cats is consistent. Cats that are entirely orange are mostly male, and those that have orange spots, such as calico or tortoiseshell cats, are always female. Because of this, scientists have long suspected that mutations related to the X chromosome that influence females are behind the orange fur in cats.
Chromosomes are forms where strands of deoxyribonucleic acid (DNA), which are genetic material, are wrapped around proteins serving as scaffolds. They are largely invisible because 95% consists of water, but they were named this because staining shows well.
Male cats have only one X chromosome, so if they inherit the orange gene, their fur turns orange. In contrast, females have two X chromosomes, so they need to inherit two orange genes to have completely orange fur. If a female inherits one orange and one black or white gene on her X chromosomes, she will have a mottled coat like a calico or tortoiseshell cat.
Professor Sasaki said, "These mottled patterns result when one X chromosome is randomly inactivated within each cell during early development," noting that "as the cells divide, areas with different active fur color genes form, creating distinct patches." The mottled coats of cats are a classic example of X chromosome inactivation, yet the specific causative gene has not been identified.
The research team compared the DNA of orange-furred cats with that of non-orange cats. As a result, they discovered that orange-furred cats had a deletion in part of the ARHGAP36 gene. Such a deletion was not found in non-orange cats. This pattern was similarly observed in 49 cats registered in the international cat genome databases.
With the assistance of local veterinarians, the research team further examined skin samples from four calico cats. The result showed that the ARHGAP36 gene with DNA deletion was expressed much more actively in the melanocytes of the orange-colored skin regions. In contrast, it was less active in the black or white regions.
The ARHGAP36 gene is activated in various parts of the body, including the brain and hormone-secreting glands. Based on this, the researchers hypothesize that the mutations responsible for producing orange fur may also impact other traits. Professor Sasaki stated, "Many cat owners believe that the personality of cats varies with fur color and pattern," and added, "While there is no scientific evidence, it could be a very intriguing hypothesis."
Professor Sasaki said he has always loved cats. He raised 10.6 million yen (approximately 1 billion won) from cat lovers worldwide to conduct his research. He expressed, "Although I have retired from university, I hope to contribute to overcoming feline diseases and want to continue working on uncovering the orange cat gene."
Professor Sasaki plans to further study the origins of the ARHGAP36 gene and the occurrence of mutations. Since the ARHGAP36 gene also exists in humans, it is expected that research on cats could provide clues for skin cancer or hair loss.
References
Current Biology (2025), DOI: https://doi.org/10.1016/j.cub.2025.03.075
Current Biology (2025), DOI: https://doi.org/10.1016/j.cub.2025.04.055