There’s a recurring claim on the Internet that orange cats are weird, but, not having observed them, I can’t vouch for it. However, two new studies published in the prestigious journal Current Biology claim to have at least found the mutation that makes orange cats orange (and add the orange patches to calicoes and tortoiseshells). The two headlines below come from ZME Science and the Guardian respectively, and the two original papers are here (Current Biology 1, Current Biology 2).
We know that the orange mutation resides on the X chromosome, which is why most orange cats (80% of them) are males (same reason why color-blindness is more common in male humans). The two papers in Current Biology note this mutation is a large-ish deletion in a single X-linked gene ARHGAP36, encoding a Rho GTPase-activating protein. This gene, while present in other mammals, seems to be unique in cats in having mutations that affect coat color. The deletion is also responsible for the orange color in tortoiseshell and calico cats, which, having other colors whose genes reside on the X chromosome, are nearly always female (the orange patches are caused by the random inactivation, in XX females, of X chromosomes having “white” and “black” alleles as well as the “orange” gene).
Here’s the abstract of the first paper in Current Biology (link above). I’ve bolded “what you need to know”:
The Sex-linked orange mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X inactivation in female tortoiseshell and calico cats. Unlike the situation for most coat color genes, there is no apparent homolog for Sex-linked orange in other mammals. We show that Sex-linked orange is caused by a 5-kb deletion that leads to ectopic and melanocyte-specific expression of the Rho GTPase Activating Protein 36 (Arhgap36) gene. Single-cell RNA sequencing (RNA-seq) studies from fetal cat skin reveal that red/yellow hair color is caused by reduced expression of melanogenic genes that are normally activated by the melanocortin 1 receptor (Mc1r)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, but Mc1r and its ability to stimulate cAMP accumulation is intact. Instead, we show that expression of Arhgap36 in melanocytes leads to reduced levels of the PKA catalytic subunit (PKAC); thus, Sex-linked orange is genetically and biochemically downstream of Mc1r. Our findings resolve a longstanding comparative genetic puzzle, provide in vivo evidence for the ability of Arhgap36 to inhibit PKA, and reveal a molecular explanation for a charismatic color pattern with a rich genetic history.
ZME Science:
An excerpt:
In a study published today in Current Biology, Kaelin and colleagues report they’ve pinpointed the peculiar genetic mutation behind the orange coat in cats — and it’s unlike anything seen in any other mammal.
“For more than a century, orange coat color in cats has been recognized as an exception to the genetic rules that explain coloration in most mammals. Orange male cats are uniformly colored, but female cats often have a patchwork of orange and black fur, commonly referred to as tortoiseshell or calico patterns,” Kaelin told ZME Science.
Orange coloration in domestic cats almost always shows up in males. Only about 20% of all orange cats are female. Females, with two X chromosomes, need both copies of the orange gene to appear fully orange — rare. Most end up displaying a mosaic of orange and black, a patchwork quilt of fur caused by a genetic process called random X inactivation.
“The orange mutation affects a gene on the X chromosome. In mammals, males have a single X chromosome and therefore one copy of the orange gene, whereas females have two X chromosomes and two copies,” Kaelin said.
. . .Orange coloration in domestic cats almost always shows up in males. Only about 20% of all orange cats are female. Females, with two X chromosomes, need both copies of the orange gene to appear fully orange — rare. Most end up displaying a mosaic of orange and black, a patchwork quilt of fur caused by a genetic process called random X inactivation.
“The orange mutation affects a gene on the X chromosome. In mammals, males have a single X chromosome and therefore one copy of the orange gene, whereas females have two X chromosomes and two copies,” Kaelin said.
And from the Guardian:
An excerpt showing that this involved citizen science!:
. . . . the Stanford team began by collecting hundreds of cat DNA samples, visiting cat shows from California to Maryland and as far as Brazil. Researchers approached cat owners to ask whether they were willing to contribute and people were eager to participate, said Christopher Kaelin, a geneticist at Stanford and the study’s lead author.
“Cat owners and breeders are really open to genetic studies and contributing to genetic studies,” Kaelin said. “They’re very interested in their cats, and they’re very interested in talking about their cats and sending pictures, which is another big part of this study. All of that interest made it really easy to connect and collect samples.”
Collecting a sample involved sticking a cotton swab in a cat’s mouth and rubbing its cheeks to collect a small bit of DNA, Kaelin said. It’s much more challenging to collect a cheek swab from a cat than a dog, due to felines being particularly resistant to having things placed in their mouths. But researchers have learned specific techniques to distract the cats, including scratching their heads. Talking them through the process seems to help, he added.
“After doing several hundred cats, you learn what you can get away with and when you need to back off quickly,” Kaelin said.
. . .Researchers collected about 200 samples for use in the study, and in total have collected more than 3,000 samples for their research. After sequencing the DNA, they compared the sequence of orange cats to non-orange cats, which helped them locate the precise alteration: a small piece of missing DNA responsible for the orange mutation, Barsh said, near the gene known as ARHGAP36. The mutation activates that gene, which gets specifically turned on in pigment cells where it is not normally active.
“It intersects with the same pathway that is responsible for red hair in humans, but it affects that pathway in a completely different way,” Barsh said. “That’s why the study is important. This is a pathway that is required for hormonal signaling in many different cell types in many different animals, including humans. We’ve learned this pathway can be modulated in a new way to, in this case, affect hair color. But we think that that applies broadly to all cells and all tissues.”
The fact that the samples were obtained in partnership with cat lovers in the community has allowed them to have greater engagement with the public, Barsh said: “Both of those examples with cat shows and working with spay-neuter clinics are examples of how partnering with the community helps science and science education. More broadly, it advances science and no cats are harmed.”
Kaelin has attended nearly 100 cat shows, he said, and presented research dozens of times so that cat owners have the opportunity to learn about what the team is doing. Feline color genetics are a useful scientific tool for discovery, and allow researchers to communicate scientific concepts to non-scientists. “It really bridges an important gap,” Kaelin said.
So, if you have an orange cat, or even a calico or tortie, you know that one of its genes caries a large deletion that results in the red color. But I still have no idea whether there are pleiotropic effects of an orange color on temperament or behavior. Were that the case, calicos and torties would be partly weird.
**************************
This report of a six-legged cat comes from the CBC. Bitsy the cat was born with six legs, apparently resulting from the absorption of a twin while in utero. Veterinary surgeons had to remove three of the legs, converting Bitsy into a “tripod” cat. She’s now functioning well, whereas before surgery she couldn’t walk at all.
A summary:
. . . Koltun said her organization met Bitsy, named after the “Itsy Bitsy Spider” nursery rhyme, after staff got an email last month about a stray cat with extra legs growing out of her side.
As it turned out, Bitsy absorbed a littermate while she was in the womb, gaining two extra legs and a second pelvis that grew as she did.
One of the main four legs didn’t work and also needed to be removed.
At first, Koltun said, she wasn’t sure if Bitsy could be helped.
“I had a little bit of a cry when I first brought her in. Because it was just so overwhelming thinking, ‘Where is this going to take us? Will we be able to help her? Will we be able to fix this?”‘
Veterinarians at Windermere Veterinary Hospital took X-rays and determined surgery would significantly improve the cat’s quality of life.
After a procedure that took a little more than two hours, Koltun said Bitsy is recovering well.
“Within less than a day, Betsy was up using the litterbox, drinking the water all by herself. So we really couldn’t have asked for a better outcome,” she said.
Bitsy still has stitches and is taking some pain medicine but is slowly being weaned off, Koltun added.
She said a staff member at the vet clinic has been fostering the feline and may keep her.
“We’re really happy for both of them that they’ve formed this amazing bond, and we’re hoping that Bitsy’s story ends up with getting to stay with her foster mom.”
All’s well that ends well, and Bitsy is now getting along fine with three legs. Here’s a CBC video; be sure to see the pre-surgery X-ray at 0:37 where you can see an extra pelvis as well.
**************************
From a commercial site, The World’s Best Cat Litter, comes an analysis of what owning a cat will cost you each year. Not that it matters, right?
Click below to read:
An excerpt in which they compare 2019 prices to 2005 prices:
Like a lot of things in life, it costs more to own and care for a cat than it did a few years ago.
An analysis of how much it costs to own a cat in 2019 versus today shows substantial increases across the board — the total initial cost of owning a cat has increased from a range of $345-780 to $535- $2,810 today. This includes things like adoption fees and medical needs, as well as buying a litter box, toys, food & water bowls, etc.
Note that these first costs are basically setting up to get a cat:
And thee annual upkeep:
Annual costs of food, litter and the like has also increased — the same analysis shows the cost in 2019 was between $788-1,693 while today’s cost range averages between $710-2,865.
They break down the costs, but you can read the reason for the ranges at the link. One think I noted was that health insurance is recommended. I always thought it wasn’t, but here’s their explanation:
Though it may seem like a large expense upfront, pet insurance is a good investment in the long run.
Even just one emergency visit to the veterinarian can cost hundreds of dollars. Having pet insurance will help to reduce these costs and take the stress out of vet visits.
Indeed. Remember when Jack the Cat fell several stories and was severely injured? His staff, fortunately, had pet insurance, which prevented them from losing a LOT of dosh for his treatment at Boston’s Angell Memorial hospital.
But really, who would worry that much about money if they loved their cat? It does seem to me, though, that the prices are fairly high.
*********************
Lagniappe: This cat really wants to get its toy by reaching under the door. It’s apparently a game!
h/t: Wendy, Merilee, Simon, Larry, Ginger K.
Ugh. Now I’ve got to listen to the whole “Dance of the Hours.”
Over the years, we’ve had both an orange tabby (male) and a calico (female). They were wonderful, calm, happy, playful, and not at all weird. So, that deletion has no pleiotropic effect on behavior. (Well, none that we could observe in our wonderful cats.) Fascinating study!
And, I’m glad to read that Bitsy is on the mend. What a weird anomaly of development. It happens in people, too.
I don’t know about orange males, but a female orange from across the street visits us daily. She’s about the sweetest, most affectionate (and least talkative) cat I’ve had experience of. She’s a shameless lap cat.
Occasionally a male tortoiseshell or calico is seen. They are XXY males.
I’m not a cat person (sorry all), but colouring of cats is fascinating. I remember a video of a talk by a biologist on evolution with a short piece on Siamese cats and how the amount of black depends on temperature. One line (paraphrased) was something like “Want a really black Siamese, keep it in the fridge.”
PCCE writes about the value of pet insurance in connection with emergency visits to the vet. I am not sure whether there is anything like this for cats, but there is a foundation (the Mosby Foundation) that helps people who can’t afford it to cover veterinary treatment for their d*g.
Yes, there are organizations that help with cat vet bills, too. Tucson is a particularly generous city where animals are concerned. We’ve got all sorts of groups that help people adopt and care for cats and dogs who wouldn’t be able to do so properly without the help. It’s a shame, in my opinion, what’s become of many vet clinics. They gouge unnecessarily knowing the lengths pet owners will go to for their furry family members. They’ve got us over a barrel and are well aware of it. Not to get too political here, but vet clinics are a favorite acquisition for private equity who have a lot to do with this. Enough said.
I got a real kick out of the cat setting up challenges for him/herself from behind the door.
The business about orange cats being strange is a new one to me. I’ve never had one, but have known many and their temperaments seemed just as variable as any other cat.
These ‘orange’ cats are known as ‘marmalade’ cats in my particular civilisation, and they do not, in my experience, behave differently from other cats. The only weirdly behaving cats I have had are Siamese, who seem to act like chihuahuas.
As for costs, I’m glad I never even considered them. Two of my cats adopted me as refugees from my neighbours who had around 15 cats at the time. One of them was the mother of the rest, and she was glad to come to me for a respite!
Currently catless, but I do have two quail living in the basement (and that’s a long story I shall not bother you with.)
Please, please bother us!
Briefly, we bought a dozen quail and made an enclosure for them three years ago. Then a raccoon managed to climb in last year and kill all except one, who later died from wounds. So we ordered a dozen eggs online, and incubated them. Three hatched, two survived, and they were born in the depth of winter, so they have been kept in the basement. We need to put some new chicken wire on the old enclosure outside and move them out into it, but we also need to build a new enclosure for some silkie hens that are coming soon. I also have lived without shelving or hanging in my bedroom closet for four years and need my son to do that as well as these poultry jobs, whilst he is also working whenever he can as an odd job man for pay. Life is complicated! I understand that as soon as this house is finished, I shall die from my leukemia, but I would like to leave it in a habtable condition for son and his wife (when she gets a visa to come here, being Kenyan.)
Thanks. Life is complicated indeed. My sympathies and good wishes. It’s hard taking care of ourselves and the animals around us.
Love the new science and the science post.
+1
I was wondering why orange cats were mostly male. I once trapped a feral orange cat who was a female. A fairly rare cat that was basically thrown away and struggling to survive.
As a child in the 1960s, I recall having 3 orange cats. All boys. Does Trump have the same gene mutation?
I don’t know about orange cats being weird. But I do firmly believe that tuxedo cats are super chill. I will vigorously reject any contrary evidence in order to preserve my faith in this.
Those numbers for cats look about right from memory.
If you want to go REALLY bankrupt though…. get a dog!
D.A. (and his dog “Aussie”)
NYC
We had an older retired racing greyhound (“Wiggins”). If they are winners, they are retired after maybe 6-7 years? Not sure. But he was the sweetest and most elegant 90lb couch potato made of pure muscle. Glorious on the open run, and gloriously expensive in the area of dental care.
I’ve had 2 male orange cats and they both were sweet, gentle, and very intelligent. One knew how to open the fridge by putting his paw between the rubber and the fridge body. He would open the fridge then eat various fudz inside. The second orange was the Alpha Kitteh for my feline family of 5 (including Alpha.) He groomed everybody daily and rarely fought. He died at age 19.5 years from cardiomyopathy.
I’m glad Bitsy is doing well. Poor kitteh.
Glad that Bitsy is on the mend. That lagniappe was fantastic!
God Bless you and your family for taking care of her. Advice for you to ask the Dr.s that did the surgery ask them about the legs for her l ve seen them do it for other animals prosthetic legs for her ask about it can’t lose it’ll be easier for her . And it’ll be on them not you . Ok good luck and GOD BLESS YOU in many ways 😻😺🌹🌹🤞🤞💞💞❤️❤️
I’m afraid that you’re mistaken – I’m not involved with taking care of Bitsy in any way, just another WEIT poster glad that she is recovering well.
I expect that her veterinary surgeon has considered the possibilities of prosthetics given the complicated surgery that she has undergone.