What makes some cats ginger? Scientists finally have an answer

Scientists have finally uncovered the genetic mutation responsible for the orange coloration in domestic cats, solving a mystery that has puzzled researchers for years. Two research teams have independently discovered a specific deletion mutation in the ARHGAP36 gene on the X chromosome as the key factor behind the vibrant orange fur seen in cats.

These breakthroughs were reported in two separate studies submitted for publication in scientific journals. Both studies have identified the same gene responsible for red fur in cats, marking a significant advance in the study of feline genetics. Recent advances in genetics have revealed that the secret behind the striking orange fur in cats lies in a complex molecular process involving the ARHGAP36 gene.

For decades, scientists believed that the orange color in cats was related to mutations in the Mc1r gene. However, studies showed that most orange cats do not have Mc1r mutations, leaving researchers perplexed. The Mc1r protein determines whether skin cells called melanocytes produce dark pigment or lighter red-yellow pigment in skin or fur, but this mechanism seems to work independently of the activation of the Mc1r gene in orange cats.

Geneticist Greg Barsh from Stanford University led one of the research teams that focused on the ARHGAP36 gene. "That was a genetic riddle, a mystery," Barsh stated, according to Der Standard. He and his team collected skin samples from four orange-colored cat fetuses and four of other colors at sterilization and castration clinics to investigate the genetic basis of coloration. By analyzing the genetic sequence of ARHGAP36 in orange cats, they discovered that these cats did not have mutations in the gene that encodes the ARHGAP36 protein.

Instead, Barsh's team found that orange cats had an abnormally high amount of RNA from ARHGAP36, 13 times greater than in cats of other colors. This suggested that the deletion in the ARHGAP36 gene alters regulation in a way that favors the production of pheomelanin, the pigment responsible for the orange color in cats, while transforming black-brown pigment (eumelanin) into orange pigment.

Developmental biologist Hiroyuki Sasaki from Kyushu University led the second research team that reached the same conclusion independently.

The ARHGAP36 gene is located on the X chromosome. In female mammals, which have two X chromosomes, one of them is randomly inactivated in each cell during embryonic development, a process known as X chromosome inactivation (XCI). This process results in mosaic patterns in female cats, leading to unique patterns like those of calico or tortoiseshell cats, where orange is combined with other colors like black or white.

"It's a gene that has been expected for a long time," Dr. Leslie Lyons, a geneticist at the University of Missouri, stated. "Domestic cats offer an excellent opportunity to study the function and regulation of genes, due to their phenotypic and genetic diversity," she added. 

This article was written in collaboration with generative AI company Alchemiq