Scientific discovery may solve 10,000-year-old mystery inside calico cat's fur

In the past, there have been many similar scientific discoveries made by two independent research groups from two different countries. For example, in the 18th century, two scientists, Joseph Priestley, an Englishman, and Carl Wilhelm Scheele, a Swede, discovered oxygen together.

And now, in a relatively rare academic event, new knowledge has been discovered almost simultaneously, by two research teams working independently. Interestingly, they were located a world apart and had no knowledge of each other's work.

That's the job of decoding the orange color of cats: Why are almost all orange cats male ? And calico cats can only be female ?

In this photo, the orange cat is definitely male. The other two cats, the calico and orange-black, are definitely female. But why?

The sex of cats has been a mystery for the 10,000 years since humans domesticated the animals. Sixty years ago, scientists thought they had the answer.

But it turns out that was only half the puzzle, and it took two research groups in the US and Japan working independently to finally solve the mystery.

They published their new findings together on bioRxiv, a pre-peer scientific publishing platform. The Japanese team published them a day early, perhaps simply because the sun rises earlier in Japan than in the United States.

This is an example of how fierce scientific competition is between research groups around the world.

From the dawn of human agriculture

About 10,000 years ago, during the dawn of human agriculture, when our ancestors Homo Sapiens began to cultivate food, in an area called Mesopotamia, located between what is now Asia and Europe, a Tom and Jerry-like chase took place.

A mouse, while running away from a cat, accidentally entered a human grain warehouse, the first warehouses to exist after the time when our ancestors only knew how to eat fur in holes and gather to survive.

Now they knew how to grow crops and store them. And only when they knew how to store them could granaries be built.

The mouse got into the grain store, it escaped the cat - at that time still a wild animal, living deep in the forest. And when returning to the nest, the mouse gathered a series of its kind to attack the grain store of humans, a warm place where they could eat and dress comfortably, without worrying about hunger and cold.

The invasion of rats made the humans very angry. Because the rats were so small and fast, they could not be caught. No matter how much they covered their grain storages, the rats would find a way to bite and get in.

So, reluctantly, humans had to share part of the fruits of their daily labor with the mice. Until cats appeared and roamed around the human settlement.

They wondered: Why were these furry, alert, meowing creatures here? Turns out, they were there to catch mice. And so, as if they had struck gold, humans began letting cats into their homes to guard their grain stores.

They were grateful to the cat, worshiping it in temples ever since.

Humans have been grateful to cats, worshiping them in temples ever since.

Wherever they go, on nomadic migrations, moving across continents or sailing to conquer new lands in the ocean, humans must bring cats along to catch mice, in order to protect their food reserves.

So over a period of several thousand years, this hairy creature began to invade the world, from a tool to a friend, a god of luck and now our "boss".

The Breeding of Cats and the Mystery of the Calico Cat

As cats followed humans around the world, they didn't just visit new lands, see new sights, and eat new delicacies—mostly birds and mice. They also had the opportunity to meet local cat populations, where they might find a mate—and often a one-night stand.

So you can imagine a very "playful" orange-coated Egyptian male cat, carried along on human merchant ships sailing along Mediterranean port cities, where he would meet and mate repeatedly with the native black-coated female cats.

A few years later when the ocean liner returned along the same route it had taken, the sailors noticed that the coat colors of the cats in the harbor had changed.

Some have orange fur, some have black fur, and some have a mix of black, orange, and white. The strange thing is that all the orange cats are male, and any cat with orange and black fur mixed together is female.

It is very rare to find a calico cat that is male and a female cat that is completely orange. The odds are about 1 in 3000.

" It's really a genetic mystery, a real puzzle ," said Stanford University geneticist Professor Greg Barsh. It wasn't until the 20th century that the mystery of cat color and sex was partially solved, when scientists discovered that the X and Y chromosomes are responsible for sex.

As it turns out, part of the gene responsible for a cat's coat color is found on the X chromosome . And a male cat is born with only one X chromosome in the XY pair, so he can only have a single-color coat.

In contrast, female cats that carry both XX chromosomes will have a mix of black and orange fur. And when combined with the white base hairs, which both black and orange cats can have, then the new female calico cats are born.

But which gene on the X chromosome determines a cat's coat color exactly?

That remains the other half of the mystery, which scientists have been unable to solve for the past 60 years. The reason is that the cat's X chromosome has 155 million base pairs of A, X, T, G and more than 1,000 genes, making it difficult to screen.

But in a new study published on bioRxiv, a pre-peer scientific publishing platform, Stanford professor Greg Barsh and his colleagues say they have finally found it, the gene that makes male cats orange and female cats calico.

To do this, Professor Barsh went to cat spaying clinics and obtained eight cat fetuses, four of which had orange fur. He then isolated the RNA present in their skin cells and found that the RNA encoding a gene called Arhgap36 was present at 13 times higher concentrations in orange cats.

This gene is also located on the cat's X chromosome, so Professor Barsh suspected that this was what created orange male cats and calico female cats.

The Arhgap36 gene is responsible for the orange color in cats' fur.

To test their hypothesis, the team sequenced the genomes of 188 cats, including 145 orange cats, six calico/tortoiseshell cats, and 37 cats with solid coats that were not orange.

The results showed that the orange and calico cats did carry a mutant version of the Arhgap36 gene, in which a piece of DNA about 5 kilobases long, or 5,000 base pairs, was missing.

' Overall, these observations provide strong genetic and genomic evidence that the 5kb deletion causes sex-linked orange colouration in cats ,' said Professor Barsh.

Interestingly, just a day earlier, a similar discovery was published on bioRxiv by an independent research team from Kyushu University in Japan. This paper shows that scientists in Japan also know that the gene Arhgap36 is the agent that creates orange color in cat fur.

It is possible that when the two research teams learned of each other's work, they immediately announced their new findings to compete for the title of being the first to decipher the mystery of the orange hairs of cats.

In the past, there have been many similar scientific discoveries made by two independent research groups. For example, in the 18th century, two scientists, Joseph Priestley, an Englishman, and Carl Wilhelm Scheele, a Swede, discovered oxygen.

In 1930, two American scientists, Clyde Tombaugh and Percival Lowell, almost simultaneously discovered Pluto, when they pointed their telescopes at the sky.

The advantage of these coincidental independent studies is that they save scientists the extra time of having to re-verify their findings, one of the basic principles of science.

The knowledge from there can therefore be established immediately. So, just as the existence of oxygen and Pluto has been confirmed, we can also be certain that the orange colour of cats comes from the Arhgap36 gene on their X chromosome.

That mystery has been completely solved.