Scientists Uncover the Gene Behind Orange Fur in Cats After 60 Years of Research

 

After decades of speculation, geneticists have finally pinpointed the gene responsible for the orange coloration in domestic cats. Two independent research teams have identified that the distinctive fiery fur seen in many cats is due to a missing segment of DNA in a non-protein-coding region of their genome.

"It's been a long-standing genetic puzzle," said Greg Barsh, a geneticist at Stanford University, speaking to Sara Reardon of Science. Barsh and his team found that skin cells from cats with orange fur produce 13 times more RNA from a gene called Arhgap36 compared to those from cats without orange fur.

Initially, the researchers expected to find a mutation in the protein-coding part of Arhgap36. However, they were surprised to discover that the mutation lies in a preceding sequence, where a 5 kilobase segment of DNA is deleted, affecting how the gene is expressed.

This 5 kb deletion was consistent across all the orange cats studied—145 out of 188 cats from a database, which included orange, calico/tortoiseshell, and non-orange cats. The study also confirmed an expected link: the gene mutation is located on the X chromosome. This explains why orange cats tend to be predominantly male, while female cats usually display a mix of colors, such as calico or tortoiseshell patterns.

"These findings provide strong genetic evidence that this deletion is responsible for sex-linked orange fur," Barsh and his colleagues concluded in their paper.

For millennia, humans have been curious about the wide variety of kitten colors produced by different combinations of black and orange-furred parents. While male kittens typically inherit either the black or orange fur from their parents, female kittens may have a mix, resulting in calico or tortoiseshell patterns.

The mutation's presence on the X chromosome means that male cats, with only one X, typically inherit the orange fur, while female cats inherit two X chromosomes, each potentially carrying different versions of the gene. In females, one of the X chromosomes in each cell is randomly deactivated, leading to a mosaic of fur colors, with some areas of orange fur and others of black or white. In rare cases, when both X chromosomes carry the mutation, a female cat can have entirely orange fur.

The idea that orange cats might not be as bright as other cats is a popular stereotype, but there's no scientific evidence to support this claim. There is no known link between this gene mutation and cognitive or health issues.

Arhgap36 has been associated with developmental issues in other animals when it is either overactive or underactive. However, in orange cats, it is only overexpressed in melanocytes—the pigment-producing cells in the skin—leading to the distinct orange coloration.

The study also clarified the difference between calico and tortoiseshell cats: calicos have an additional white spotting mutation that affects melanocyte survival and migration, contributing to their distinctive color patterns.

A second study led by Hidehiro Toh at Kyushu University also confirmed Arhgap36 as the gene responsible for orange fur. This research showed that increased expression of Arhgap36 suppresses genes responsible for darker pigments, shifting the cat’s fur color from brown or black to the characteristic reddish-yellow hue of orange fur.