After 60 years of searching, geneticists discovered the gene responsible for the marmalade coloration in domestic cats.

Two separate research teams discovered that any fiery-coloured fur on our precious clawed feet is probably caused by a missing DNA fragment in a region of the cat's genome that does not code for proteins. "It's been a genetic mystery, a conundrum," Stanford University geneticist Greg Barsh revealed.

Barsh and his colleagues observed that cat skin cells with orange fur sprouts express 13 times more RNA from the Arhgap36 gene than skin cells from cats without orange hair. The researchers expected to detect a mutation in the protein-coding region of the overproductive Arhgap36 gene, but instead discovered a deletion in the sequence preceding it, which presumably affected the rest of the gene's production. The 5 kilobase deletion was found in every orange cat the researchers analyzed from a database of 188 cats, including 145 orange, 6 calico/tortoishell, and 37 nonorange cats.


One finding came as no surprise. As previously expected, the defective gene is placed on the cat's X chromosome, which explains why the orange hue appears differently in the sexes. The majority of orange cats are male, although most female cats with some orange fur develop patchworks of various hues.

A black & orange cat can give birth to kittens of various colours

The fact that a black cat and an orange cat can give birth to an unexpected variety of kitten colours has intrigued people since humans and cats first coexisted about 10,000 years ago.
As may be expected, the majority of the male kittens from this mating are either orange or black.

 Both groups confirmed that the X chromosome contains the mutation that causes orange fur, which explains why there can be such pronounced variations in colour patterning between the sexes.
Females have two copies of this mutation, one on each of the Xs they inherit from each parent, in contrast to males who only have one copy on their single X chromosome.

 Rarely, when the mutation is present in both X chromosomes, the female develops into a hairy fireball that is as ginger as any man. It has taken scientists 60 years to figure out the gene that causes orange cats, which are typically male kittens.

As it happens, orange cats have a humorous reputation for being the least intelligent of their kind. Despite anecdotal evidence, there is no scientific evidence linking cat colouration to intellect, and there are no apparent detrimental effects on mental or physical health from this mutation.

When Arhgap36 functions excessively or insufficiently, it might lead to developmental issues in other animals. However, it appears that only the melanocytes—developing and mature pigment cells—in orange cats exhibit overexpression of the gene.

 Arhgap36 was also shown to be the orange cat fur gene in the second study, which was headed by geneticist Hidehiro Toh of Kyushu University. They discovered that increased expression of this gene suppresses genes related to colour pigments, causing the reddish to yellow pheomelanin pigments to replace the dark brown to black eumelanin pigments.