Geneticists finally solve the mystery behind Garfield’s orange coat

Garfield, the star of Jim Davis’ 1978 cartoon of the same name, is orange, like many of the cats that roam our homes. He’s orange, just as some people are red-haired, some horses are brown, and some dogs are Irish Setters, but with one important difference.

The cause of this distinctive coloration is known for all other animals, including red-haired humans, but surprisingly, until now it has been unknown for cats, or felines in general. It was.

Two papers describing the genetics behind orange cats have been published on bioRxiv, one of the most popular pre-publication repositories for unpeer-reviewed papers. One of them comes from Greg Bursch’s lab at Stanford University in California. The other person is from Hiroyuki Sasaki’s laboratory at Kyushu University.

Eumelanin and pheomelanin: two mammalian pigments

Mammals only have two pigments. It is melanin of two colors: eumelanin (dark brown, blackish) and pheomelanin (yellowish, reddish, or orange). Redheads produce only pheomelanin, while dark-skinned people mainly accumulate eumelanin. Thanks to the 700 genes that control pigmentation in animals, all other skin and hair colors fall somewhere in between.

In primates, horses, rodents, dogs, cows, and many other animals, the decision to produce melanin and to produce eumelanin or pheomelanin rests in the hands of a membrane protein called MC1R. It controls skin cells known as melanocytes that release melanin. When melanocyte-stimulating hormone (α-MSH) is released, melanocytes begin producing eumelanin. When antagonists such as agouti signaling protein or canine beta defensin act, the production of black eumelanin is stopped and melanocytes produce orange pheomelanin instead.

However, cats are a completely different matter. Anyone who has a cat in their home knows that cats are very unique animals and are very special in every way. And that also applies to pigmentation.

In cats, eumelanin or pheomelanin production is not controlled by MC1R receptors. Instead, it is in the hands of a genetic locus (the gene for which was previously unknown) called “orange.” A locus is a physical location in the genome whose effect is known (e.g., black or orange coat), but details of the exact DNA sequence it contains or the gene to which it belongs are unknown. is.

For this reason, we typically first identify the locus and then take the time to discover and describe the associated genes in detail. There are two versions of the orange locus in cats: the “O” mutant (orange), which supports the production of pheomelanin, and the “O” mutant (black), which is responsible for the production of eumelanin.

One detail to note is that the orange locus is on the X chromosome. Like other mammals, female cats are XX and male cats are XY. And, like all female mammals, throughout development, every cell randomly inactivates one of its two copies of the X chromosome. Oo female cats with the O variant on one X chromosome and the O variant on the other X chromosome will have parts of their body orange (areas where the ‘o’ allele is inactivated). , other areas turn black (if inactivated). “O” allele).

This means that when you see a bicolor (black/orange) or tricolor (black/orange/white) cat, or a diluted version of it, you know it must be female and its pigmentation pattern is completely It means you know it’s unique.

Male cats are orange or black (they only have one X chromosome), but they are dichromatic unless they have a chromosomal change equivalent to Klinefelter syndrome in humans (males are born with an extra X chromosome). Or it won’t be three colors.

calico cat

Therefore, females can have a unique mosaic pattern that is prized by cat lovers. Coinciding with another mutation that affects melanocyte proliferation and differentiation (producing white spots with no pigmentation) produces a tricolored cat, commonly known as a calico cat.

Each calico cat is unique because one of the X chromosomes in each pigment cell is randomly inactivated during development. The earlier this inactivation occurs during development, the larger the resulting spot will be. The later the development, the smaller the spots.

Gene for orange fur in cats

Until now, we didn’t know which genes were hidden behind the orange locus in cats. Recent work by Barsh and Sasaki identified that this is not the cat homolog of MC1R, but a separate gene, the Arhgap36 gene. Similar to the orange spots in calico cats, male cats with orange fur have a mutation in this gene that blocks the production of eumelanin and allows the production of pheomelanin.

These two studies are great examples of good basic, solid research. This research is intended solely to satisfy scientific curiosity, without knowing its direct application, in this case to understand why that naughty cat Garfield is orange.

This article is republished from The Conversation under a Creative Commons license. Read the original article.