Orange cats tend to have a reputation. People call them original, affectionate, chaotic or simply a little strange.
But although their behavior can be in debate, their color has always raised a clear genetic question.
Today, a new study carried out at the University of Stanford has identified a suppression on the X chromosome which lights a normally silent gene in pigment cells, causing orange fur.
The results were published in Current biology.
A genetic mystery with a long history
Orange fur in domestic cats shows a strong link with sex, most orange cats being men. This scheme has been noticed since the early 1900s, informing scientists that the responsible gene is most likely on the X chromosome. Any male cat who inherits his orange, while female cats, with two X chromosomes, need two copies of the gene to do the same. Female cats can be orange, but it’s rare – usually they are a patchwork of orange and black (Ouclace or Calicot turtle).
Unlike other mammals with orange shades – tigers, golden retrievers and humans with red hair – Cat Orange is not linked to usual pigment genes (like MC1R Or Asip).
“In a number of species that have a yellow or orange pigment, these changes occur almost exclusively in one of the two genes, and none of these genes is linked to sex,” said the main author Dr Christopher KaelinA research professional in life sciences in the genetic department of the University of Stanford.
Scientists had an approximate idea where the MUse in cats could be, but nothing was confirmed – it was an aberrant genetic value.
Among cats, the color is delivered with a mystery: an inherited trait, clearly linked to sex, but missing the usual genetic suspects.
“It is a genetic exception that was noticed over a hundred years ago,” said Kaelin. “It is this comparative genetic puzzle that motivated our interest in orange linked to sex.”
Using previous workKaelin and his colleagues decided to find the exact mutation responsible for orange fur in domestic cats and understand why this line behaves so different from similar colors in other mammals.
Identify the mutation behind the ginger fur
The team has used new genomic resources, including comprehensive genomes sequences of many cat breeds and DNA samples collected in sterilization and sterilization clinics across the United States.
“Our ability to do so was rendered by the development of genomic resources for the cat which has become available in the last 5 or 10 years,” said Kaelin.
They focused on male orange cats because males have only one chromosome X, any mutation on this subject would appear clearly. By comparing their DNA, the researchers found 51 variants shared by orange males. They then excluded the most by checking non -orange cats, leaving only three remaining variants.
One of them, a small abolition of 5,000 basins, stood out. It was linked to a higher activity in a neighboring gene called ARHGAP36.
The team confirmed that the abolition was present in the 145 orange cats and absent from 37 non -orange cats, strengthening its link with the color of the coat.
“As we found it, the ARHGAP36 Gene had no connection with pigmentation, “said Kaelin.
Using the sequencing of the unique RNA of the fetal cat skin, the team found that in orange cats, ARHGAP36 was on in pigment cells; However, among non -orange cats and other mammals, this was not the case.
“”Arghap36 is not expressed in mouse pigment cells, human pigment cells or pigment cells of non -orange cat cats. Orange cat mutation seems to light up Arghap36 Expression in a type of cell, the pigment cell, where it is normally expressed, ”added Kaelin.
This bet seems to block part of the MC1R signaling pathway, which generally leads to the production of black or brown pigments. Instead, pigment cells produce orange default.
Unlike other species where orange coloring disrupts the first stages of pigment production, cat mutation acts later in the track, blocking the function of a key signaling molecule downstream of MC1R.
The team confirmed that ARHGAP36 is only activated in the skin of orange cats. Other organs have shown no change, suggesting that the effect is specific to pigment cells.
“Certainly, it is a very unusual mechanism where you obtain the betspression of a gene in a specific type of cell,” said Kaelin.
To test the effect of ARHGAP36The researchers introduced the gene into human pigment cells, where it has reduced PKAC levels – an essential protein to activate pigment genes.
Evolving history behind the ginger cat gene
The results show how an unrelated gene known with color can play a new role. This switch in the location, not the function, creates a visible line.
“We believe that this is an example of how genes acquire new functions that allow adaptation,” said Kaelin.
This type of regulatory recreation – sometimes called molecular DIY – is a common theme in evolution. The mutation of the orange cat shows how changes in gene regulation, rather than the structure of the genes, can cause lines.
The team noted that all the orange cats of their study carried the same piece of DNA around the mutation, pointing to a single origin for the line at least 900 years ago.
“This is something that appeared in domestic cats, probably at the start of the domestication process,” said Kaelin. “We know that because there are paintings that date from the 12th century where you see clear images of Calico Cats. So the mutation is quite old.”
Could this unusual genetic discovery also play a role in the questionable behavior of ginger cats?
“The expectation, on the basis of our observations, is that this is very specific to pigment cells,” said Kaelin.
“I don’t think we can exclude the possibility that there is a modified expression of the gene in certain tissues that we have not tested that could affect behavior,” he added.
However, he suspects that the stereotype of the cat in ginger is more a matter of gender than genetics – most orange cats are men.
“There are not many scientific studies on the personality of orange cats,” he noted.
Reference: Kaelin CB, McGowan Ka, Trotman JC, et al. Molecular and genetic characterization of the color of the orange coat linked to sex in domestic cats. Biol Curr. 2025. Doi: 10.1016 / J.Cub .2025.04.055
This article is a resumption of a press release published by Stanford Medicine. The material has been modified for duration and content.