Scientists Identify Gene Behind Orange Fur In Cats

After six decades of research, scientists have discovered the gene responsible for the orange fur seen in domestic cats. Two separate research teams found that the characteristic ginger, calico, and tortoiseshell colours in cats are due to a missing piece of DNA in a part of the cat's genome that doesn't make proteins. This breakthrough explains why some cats have their distinctive fiery fur.

"The sex-linked orange mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X-inactivation in female tortoiseshell and calico cats. Unlike the situation for most coat colour genes, there is no apparent homolog for sex-linked orange in other mammals," the authors of the study wrote.

"We show that the sex-linked orange is caused by a 5 kb deletion that leads to ectopic and melanocyte-specific expression of the Rho GTPase Activating Protein 36 (Arhgap36) gene. Single-cell RNA-seq studies from foetal cat skin reveal that red/yellow hair colour is caused by reduced expression of melanogenic genes that are normally activated by the melanocortin 1 receptor (Mc1r)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, but the Mc1r gene and its ability to stimulate cAMP accumulation are intact."

"Instead, we show that increased expression of Arhgap36 in melanocytes leads to reduced levels of the PKA catalytic subunit (PKAC); thus, sex-linked orange is genetically and biochemically downstream of Mc1r. Our findings solve a comparative genomic conundrum, provide in vivo evidence for the ability of Arhgap36 to inhibit PKA, and reveal a molecular explanation for a charismatic colour pattern with a rich genetic history."

"I am fully convinced this is the gene and am happy," Carolyn Brown, a University of British Columbia geneticist who was not involved in either study, told Science. "It's a question I've always wanted the answer to."

As per a release, scientists have long been fascinated by tortoiseshell and calico cats: the offspring of a black cat and an orange cat. Multicoloured cats from such a cross are almost always female, suggesting the gene variant that makes fur orange or black is located on the X chromosome. The male offspring of such a cross are typically unicolor because they inherit just one parent's X chromosome: We can guess, for instance, that Garfield's mother is orange because he inherited his only X chromosome from her.