Some scientific mysteries seem like little at first glance, but they hide great complexity. One of them, who was wearing decades unresolvedis the genetic reason behind the orange (or red) color in domestic cats. Although the origin of reddish fur had been identified in other mammals, such as chestnut horses or red-haired people, the case of felines was an enigma… Until now.
Two teams of researchers, one led by Greg Barsh at Stanford University (United States) and another by Hiroyuki Sasaki at Kyushu University (Japan), have identified the specific gene that explains this characteristic trait. Both studies, published as prepaints in bioRxiv, they conclude that orange color in cats is linked to a mutation in the ARHGAP36 genelocated on the X chromosome.
This discovery, beyond curiosity, provides valuable information about the genetics of pigmentation and how genes regulate color patterns in mammals.
How is fur color generated in mammals?
To understand this finding, it is first important to explain how hair color is formed in mammals. There are two basic pigments responsible for the tones in hair:
- The eumelaninwhich generates dark tones, from brown to black.
- The pheomelaninwhich produces lighter colors, such as yellow, reddish or orange.
He balance Between these two pigments is what determines the color of the coat. In most mammals, this process is regulated by a gene called MC1R (melanocortin-1 receptor), which acts as a switch:
- When active, cells produce eumelanin (dark color).
- When inactive, pheomelanin (light color) is produced.
However, In cats, this mechanism works differentlywhich had baffled scientists for years.
The mystery of the ‘Orange’ gene in cats
Cats have a special gene called a locus orange (O/o), which controls the production of pheomelanin (orange color) and eumelanin (black/brown). This gene is not related to MC1R, but rather resides on the X sex chromosome.
What are alleles? Within the gene locus orangethere are two versions, known as alleles:
- O allele (orange): causes the cat to produce pheomelanin and have orange fur.
- Allele o (non-orange): allows the production of eumelanin, resulting in black or brown cats.
How the color orange is inherited: The inheritance of the orange color in cats is interesting and somewhat peculiar, mainly because it is related to the X chromosome.
- Males (XY): Male cats have a single X chromosome. This means they can only inherit one allele from their mother. If they inherit the O allele, they will be completely orange. If they inherit the o allele, their fur will be black or brown.
- Females (XX): Cats have two X chromosomes, which allows them to inherit two different alleles. This means that they can have combinations of the O and o alleles. For example, if a cat has an O allele and an o allele (Oo), her coat will have a combined pattern of black and orange, resulting in tricolor cats, known as tortoises and calicoes.
X chromosome inactivation: The reason female cats can show these color patterns is due to a phenomenon called X chromosome inactivation. During embryonic development, each cat cell inactivates one of its X chromosomes randomly. This means that some cells will use the O allele and others the o allele, thus creating the whimsical coat we see in tortoise and calico cats.
The discovery of the ARHGAP36 gene
Until now, it was not known which specific gene was behind the locus orange. Recent studies have identified that the gene responsible is ARHGAP36, and its functioning is quite particular.
The ARHGAP36 gene regulates pigment production by influencing the activity of a protein called protein kinase A (PKA). When the ARHGAP36 gene is active, it has the effect of inhibiting the action of PKA. This inhibition is essential, since PKA normally facilitates the production of eumelanin, the pigment responsible for dark coat colors. Therefore, when ARHGAP36 is up and running, eumelanin production is blockedallowing the pigment cells to only generate pheomelanin, the pigment that gives rise to the characteristic orange coat of many cats.
The Stanford team discovered that red (or orange) cats have a genetic deletion, i.e. a small segment of DNA that has been deleted, in a regulatory region of the ARHGAP36 gene. This mutation causes the gene to be expressed abnormally highly, which in turn blocks the production of dark pigment. As a result, the production of pheomelanin is favored, giving rise to the distinctive orange coat.
How was this conclusion reached?
First, studies were carried out on embryonic skin samples from cats at different stages of their development. When examining these samples, the scientists noticed that in the embryos that would later develop as orange cats, the ARHGAP36 gene had abnormally high expression levels, which provided clues that there was a direct relationship between the activity of this gene and the coat coloring.
Additionally, the researchers carried out extensive genetic sequencing, analyzing the genomes of more than 400 cats from various origins. This analysis revealed that all orange and calico cats shared the same mutation in the ARHGAP36 gene, which was a crucial discovery by establishing a clear genetic link between the mutation and specific coat coloration.
Finally, the strength of this finding was seen reinforced by the fact that both teams of research, one located in the United States and the other in Japan, they came to the same conclusion independently. This coincidence validates the results and also underlines the importance of collaborative work in science.
Sometimes even the most seemingly simple mysteries, like a cat’s fur, hide fascinating complexity that can reveal fundamental principles of biology.
In this Instagram video we can see Yukine, whose color is called bicolor red point, and Hinata, a red tabby mackerel.
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