Genetic mutation makes orange cats unique

A group of scientists have discovered the genetic mutation that turns some cats orange, a condition that does not occur in any other mammal and, in this case, is linked to sex, being more common among males.

The study, led by Christopher Kaelin of Stanford University (California), and published Thursday in the journal Current Biology, reveals a unique link between the feline X chromosome and the orange hue of their fur.

Many mammals — such as tigers, golden retrievers, and even red-haired humans — have red hair, but according to Kaelin, “in none of these cases is it related to sex.”

The mutation, which they dubbed “sex-linked orange,” is located on the X chromosome, meaning that, among cats alone, this shade is more present in males than in females.

As with most mammals, females have two of these chromosomes, and males have one X and one Y.

Therefore, for a male cat to be orange, this variation only needs to occur once, on his X chromosome, while female cats need it to occur on both, which is less likely, the scientists indicated in the research.

“Cats with a single copy of the mutation exhibit a partially orange coat with a spotted pattern known as ‘tortoiseshell,’ or with orange, black and white spots known as ‘calico,’” they explained.

This discovery established the “genetic exception identified more than a hundred years ago,” according to Kaelin, which until now had no answer.

After analyzing about fifty variants of the X chromosome shared in orange cats and eliminating those that also occurred in other colors, they found Arhgap36, an activating protein that until now had not been associated with pigmentation.

This gene is normally expressed in neuroendocrine tissues — where the nervous and endocrine systems interact — and was being studied in the areas of cancer and developmental biology.

“Arhgap36 is not expressed in pigment cells of non-orange mice, humans or cats,” Kaelin said.

“However, the mutation in orange cats appears to activate Arhgap36 expression in the pigment cell,” he added.

The study coordinator described this phenomenon as “very unusual” and said that these discoveries are a gateway to understanding how other physical characteristics arise, such as cheetahs’ spots or dolphins’ body shape.

Despite the influence on color, the study did not find that Arhgap36 expression influenced tissues other than skin.

“I don’t think we can completely rule out the possibility that there is altered gene expression in some tissue that we haven’t tested that could affect behavior . But I think the reputation of orange cats as lovable agents of chaos is more due to the fact that most of them are male,” Kaelin said.