Orange You Glad We Finally Figured Out Why Some Cats Are Ginger
Scientists have finally solved the greatest feline mystery of our time: Why is it, exactly, that some cats are orange?
Two separate research teams have detailed the answer in two studies published Thursday in the journal Current Biology. They've identified the precise genetic mutation in these cats that explains their orangeness—a mutation not seen in other animals with similar coloration.
Orange-furred cats are often referred to as gingers. And according to Chris Kaelin, lead author of one of the new studies, the same basic mechanism underlying red hair in humans applies to orange cats, too: their pigment cells switch from making eumelanin pigment (brown/black) to making pheomelanin pigment (red/orange). But scientists have known for a while that the genetic cause of orangeness in cats is very different from the one in humans and other mammals.
'What motivated us to study orange cats is that the trait is sex-linked (the mutation and the affected gene are on the X chromosome) and sex-linked pigmentation traits are not observed in other species,' Kaelin, a geneticist at Stanford University, told Gizmodo in an email. 'So, we recognized that orange cats provided an opportunity to learn something new and potentially insightful.'
The location of this mutation also explains why ginger cats tend to be male (males only possess one X chromosome). Previous studies have narrowed down the mutation's likely location on the X chromosome, but thanks to more comprehensive genomic data from a variety of cats, Kaelin's team and a separate research team from Japan were independently able to isolate the specific genetic quirk underpinning a cat's gingerosity.
'We used genetic approaches to pinpoint a mutation, a small deletion of sequence on the X chromosome, that causes orange color. All orange cats have this deletion, but non-orange cats do not,' Kaelin explained. 'The mutation is not located in a gene (the part of the genome that encodes for proteins). Instead, it's in what we call a non-coding region—the remaining 98% of the genome that does not code for proteins.'
According to Kaelin, the mutation activates a nearby gene called Arhgap36 so that it's expressed in pigment cells when it normally shouldn't be. The activation then blocks eumelanin pigment from being produced, causing pheomelanin to be made in its place by default. While genetic variants that trigger orangeness in other animals interact with this same pathway as well, the ginger cat mutation is stranger still because it disturbs a later step of this process. Interestingly, this marks the first time Arhgap36 has been linked to pigmentation.
'This type of mutation is very unusual,' Kaelin notes.
The team's discovery doesn't explain everything about why orange cats are the way they are. These felines are commonly depicted as especially dim or mischievous, to the point that they're said to possess a single brain cell that must be shared among all orange cats in the world. But the researchers found no evidence that their mutation causes any other changes, including those related to behavior or temperament.
'One of the key findings of our study is that we observe altered activity of the affected gene in pigment cells, but remarkably not in other cells or tissues including brain areas where the gene is normally expressed,' Kaelin said. 'This suggests that the mutation does not have broad effects.'
While the single brain cell theory will have to await more scientific inquiry, the researchers do think their work can lead to more insights. Simply figuring out how this deletion can activate Arhgap36 so precisely might open up a whole new bag of intriguing discoveries waiting to be explored further.
'We would like to understand how the deletion has such a remarkably specific effect on gene activity and we expect that answering this question will have broad implications about how mammalian genes are turned on and off in specific cell types,' Kaelin said.
So if you have an orange cat in your life, be sure to thank them for their contribution to science with some extra treats today.
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But of all the known parasite-host associations on the planet, only a tiny fraction to date are known to involve behavioral manipulation. Gizmodo: You detail so many different examples of zombie parasitism that the average person might wonder; is this something I should ever be worried about? Are there any bugs out there that can or possibly could zombify people someday? Weisberger: Well, it's natural to be concerned about how this might affect you personally. And the fact is that there are some pathogens that are known to affect mammal behavior, and you probably know them already. Rabies, of course, is a very common one. Cases of rabies are recorded in texts that go back thousands of years, and it's known to affect its host's behavior very dramatically. This usually involves behavioral changes that make them more aggressive, and there's also excessive salivation involved. The thinking is that this benefits the parasite, because aggressive animals are more likely to fight. And the virus particles are shed in their saliva. So the combination of changing aggressive behavior and a lot of drool means that the rabies virus is able to increase its chances of successful reproduction. Another example you might know about is Toxoplasma gondii, which causes the disease toxoplasmosis. T. gondii's definitive hosts are cats, which means that it only can reproduce in cats. But it can live in lots of different species of birds and mammals, and that includes people. And so there's robust evidence that T. gondii changes the behavior in infected rodents. What it does in rats and mice is it reduces their fear of cats. It makes them attracted to cat urine, which is something that's normally, for good reason, a deterrent for them. It makes them bolder around cats, which means they're more likely to be eaten by cats, which means the T. gondii they are carrying will then get inside a cat where it needs to be to reproduce. But there's also evidence starting to come out in papers within the last decade or so showing that there seem to be similar types of behavioral changes in animals that are not rodents. In hyena cubs, for example, that are infected with T. gondii, they seem to be bolder around lions. And there are studies of captive chimps infected with T. gondii that seem to lose their fear of leopards, which are a natural prey of theirs. Now with humans, they're dead-end hosts. More than 2 billion people worldwide are thought to carry this pathogen, even if they don't show any symptoms or have any signs of toxoplasmosis. And there's also a growing body of evidence hinting that T. gondii can change human behavior, even if the person doesn't show any other symptoms, and in similar kinds of ways where the person with T. gondii will be bolder or more aggressive. But figuring out what actually makes a specific behavioral change is very complicated. And it's even more complicated in people compared to figuring out what changes behavior in an ant, for example. So there is still, at this point, a lot of work to be done to be certain that you can separate out these specific changes and link them to T. gondii, rather than there being other factors involved. But it's definitely an interesting area of study. Gizmodo: Speaking of unresolved questions, what are some of the biggest mysteries left to be solved about these zombifying parasites? Weisberger: Well, if you look at the history of how scientists have studied behavior manipulation and zombification, some of the first records of these are centuries old. And usually it just starts out with the scientist observing that an insect is either behaving in an unexpected way or that it seems to be sprouting things that are not normal. But it's only really been in the last 20 years or so that scientists have been able to drill down and look at the neurochemistry of what's going on. We're finally at that point we can start to figure out questions like: What are the proteins that are being changed? What are the genes that are being expressed? What is the parasite actually doing to its host? And one of the big questions is; is the parasite itself producing the compounds that are causing the change, or is it producing compounds that then get the insect to produce chemicals that affect its behavior? For example, there is a type of wasp that zombifies spiders. And what it does is it lays an egg on the spider, the egg hatches, and the wasp larvae essentially just piggybacks on the spider. It just sits there discretely sipping the spider's hemolymph [the invertebrate version of blood], almost like a juice box, until it's ready to pupate. And when that happens, there is a very dramatic behavioral change in the spider. The spider starts to build a web that is completely different from the normal web it makes. You can probably picture the Charlotte's web type of web, which is a series of concentric circles with spokes. And that's a typical prey catching web. But the zombified spider builds a web that's usually used to keep it safe and secure as it molts. Once the spider is done with this web, its job is done. The wasp larvae drains it dry, the spider corpse drops to the ground, the wasp builds itself a little cocoon and then it hangs out in the wasp web—the last web that the spider ever built. So what the wasp is doing is it's stimulating in the spiders a massive amount of hormones called ecdysteroids. And the big unanswered question right now is, is the wasp producing this itself or is it stimulating it in the spider? Because spiders naturally produce these hormones just before they molt; it's actually the trigger that starts the whole process of them building this web in preparation for them having this big physical change. So in this and in many, many other examples of zombification, there is still so much to be unpacked about what the specific pathways are between the parasite and its host, about the small nudges that it's doing to cause these dramatic changes in behavior. Gizmodo: So to close things out, what's your favorite zombie bug that you learned about in writing this book? Weisberger: I was originally a filmmaker before I was a science journalist, so I'm naturally attracted to things that are very visual. And one of the most dramatic examples that caught my attention are the discofied zombie snails. So these are land snails that are infected by worms in the genus Leucochloridium. What these worms do is they infect the snails using these broodsacs, which is like these little sausages full of worm larvae. And these broodsacs are very colorful, they're usually striped, patterned in shades of brown and green depending on the species. The sacs migrate into the snails' eye stalks, and once there, they pulse, making the stalks look very much like the undulation of a crawling caterpillar. Now, the definitive hosts of these worms are birds; they have to be in a bird to reproduce. So this display, which looks like a caterpillar, is something that is uniquely attractive to hungry birds. The worm also manipulates the snail's behavior so that it will wander out into exposed spaces, rather than hunkering down in the undergrowth where it normally stays. So they're now out in the open and they have these caterpillar-looking eye stalks, making the broodsacs an enticing meal. But the eyestalks split very easily, so the broodsacs will often just pop right out, and the snail will often heal its eyestalks and be fine afterward. That's my favorite species example, but I also have a favorite specific individual zombie bug. There was a zombie ladybug that became TikTok famous in 2021, which became known as Lady Berry. There's this content creator named Tiana Gayton, who's very enamored of insects and spiders. And one day, she was in a grocery store when she looked at a head of lettuce and saw a ladybug that looked like it was hugging something. It looked like it was hugging a small cocoon. And she was like, 'Oh, this is weird. I'm going to take this ladybug home with me and see what's happening.' She took it home and she tried to pry the ladybug's legs away from the silk around the cocoon, but the ladybug refused to let go. It turned out that the ladybug was parasitized by a species of wasp that manipulates its behavior. It will lay an egg inside the host's abdomen, the egg hatches out of the ladybug and forms into a pupa, and the host then becomes the pupa's bodyguard. So the ladybug was guarding the cocoon. But Tiana Gayton was determined to save it. She pried it off the cocoon, separated it from the cocoon, and put the ladybug in a little jar. She gave it water, gave it food, and nursed it back to health. And eventually she took Lady Berry to the park and returned it to the wild. And so there's an example of a zombie that got something most zombies don't: a second chance. Rise of the Zombie Bugs: The Surprising Science of Parasitic Mind-Control, published by Johns Hopkins University Press, is now available in hardcover and as a e-book.
