Why are some cats orange? Scientists have finally found the answer

Orange cats are everywhere, from the iconic character Garfield to the independent tabby lounging in the sun. But what gives orange cats their signature color? For decades, the answer remained a mystery to scientists.

Now, researchers at Stanford Medicine and Kyushu University have cracked the code. The answer lies in a gene called Arhgap36. This gene behaves strangely in orange cats, turning their fur a vivid shade of orange.

Why orange cats are rare

Scientists have known for years that the orange trait in cats is linked to the X chromosome. Male cats, with their single X chromosome, only need one copy of the gene to flaunt their ginger fur.

Females, however, require two copies to be completely orange. Otherwise, they become calicos or tortoiseshells, their fur a patchwork of orange, black, and white.

“In a number of species that have yellow or orange pigment, those mutations almost exclusively occur in one of two genes, and neither of those genes are sex-linked,” explained Christopher Kaelin, a senior scientist in genetics and lead author of the study.

Genetic mystery of cat colors

Kaelin and his team had a hunch the answer was related to the X chromosome. But which gene? They collected DNA samples from spay and neuter clinics, comparing orange cats to non-orange cats.

After analyzing the genomes, the researchers found 51 genetic variants that could explain the orange trait. They narrowed it down to three.

One stood out: Arhgap36. A tiny deletion in this gene cranked up its activity in pigment cells. Normally, Arhgap36 keeps a low profile, mainly operating in nerve tissues and cancer cells. But in orange cats, it’s louder than a kitten demanding breakfast.

“Arhgap36 is not expressed in mouse pigment cells, in human pigment cells or in cat pigment cells from non-orange cats,” Kaelin said.

“The mutation in orange cats seems to turn on Arhgap36 expression in a cell type, the pigment cell, where it’s not normally expressed.”

Orange cats are usually male

Orange cats are predominantly male, and it all comes down to the X chromosome. Males have one X and one Y chromosome. If that X carries the orange gene, they’re entirely orange.

Females, with two X chromosomes, need the orange gene on both to sport a solid ginger coat. If a female inherits only one copy, she becomes a mosaic of orange and black.

This randomness creates the striking tortoiseshell and calico patterns. Some cells activate the orange gene, while others activate the black gene. The result? A coat that’s as unpredictable as a cat’s mood.

A shared genetic breakthrough

While Stanford scientists zeroed in on Arhgap36, researchers at Kyushu University pursued a parallel investigation. Professor Hiroyuki Sasaki and his team examined DNA from 18 cats including 10 that were orange. The findings matched those at Stanford.

“This was such strong evidence that even at this stage, we were confident that Arhgap36 was the orange gene,” said Sasaki.

The researchers expanded their study, analyzing DNA from 49 more cats, and the same pattern emerged. The Arhgap36 deletion consistently appeared in orange cats but not in others.

Origins of orange fur

Where did this mutation come from? Kaelin believes it emerged early in domestication. Ancient paintings dating back to the 12th century depict calico cats, suggesting the mutation is centuries old.

“This is something that arose in the domestic cat, probably early on in the domestication process,” Kaelin said.

Sasaki wants to dig deeper. He plans to study ancient Egyptian cat mummies, searching for the orange gene. The goal? To pinpoint when and where the mutation first appeared.

Looking at the gene beyond fur

Arhgap36 isn’t just about orange fur. In other animals, it’s linked to cancer and nerve development. Could it affect more than just a cat’s coat? Sasaki thinks so.

“For example, many cat owners swear by the idea that different coat colors and patterns are linked with different personalities,” he said. “There’s no scientific evidence for this yet, but it’s an intriguing idea and one I’d love to explore further.”

The gene could also impact brain and hormone function. Sasaki’s team found the gene active in several tissues, not just skin cells. Whether this activity alters behavior or health is still a mystery.

The discovery of Arhgap36 as the orange gene is just the beginning. Sasaki and Kaelin plan to investigate how the gene influences pigment production.

The experts are also exploring its role in cancer and skin conditions, hoping to uncover broader implications for both cats and humans.

Orange cat mystery solved

For over a century, the orange gene remained a mystery, hiding in plain sight. Now, with the discovery of Arhgap36, scientists are one step closer to understanding how cats get their colors. But the story isn’t over.

Sasaki’s ultimate goal is to recreate the mutation in cat cell cultures, observing its effects in real time. Meanwhile, Kaelin wants to map out the entire molecular pathway, tracing how a simple gene deletion transforms a basic pigment cell into a beacon of orange fur.

From the dusty streets of ancient Egypt to the modern lab, orange cats have carried this genetic quirk for centuries. And as researchers continue to peel back the layers of DNA, the secrets of these fiery felines may prove to be more profound than anyone imagined.

The study is published in the journal Current Biology.

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