Latest news with #Kaelin
Yahoo
22-05-2025
- Science
- Yahoo
Scientists solve the mystery of ginger cats – helped by hundreds of cat owners
After decades of mystery, new research has shed light on a question that has long stumped scientists and cat lovers alike – what exactly makes orange cats, well … orange? Two studies published in Current Biology last week by separate teams at Stanford University and Japan's Kyushu University at last provided some answers. Scientists have known for more than a century that orange cats inherit coloring differently from other mammals. Now – with help from hundreds of cat owners – researchers have identified the genetic mutation that gives orange cats their signature hue. 'From the time we started working on genetics of hair color, we have been fascinated to know what causes orange hair color in cats, and we know based on its inheritance that it must be different from what causes it in humans or dogs or mice or other animals,' said Greg Barsh, a professor of genetics at Stanford and the paper's senior author. 'What wasn't known is what the mechanism was.' To find out, 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. As the study progressed, cat owners began reaching out in hopes of contributing, and mailed in brushes to the researchers. Several spay-and-neuter clinics contributed tissue samples from feral cat populations. 'Then in the lab, we could extract DNA from those samples and compare. We would then sequence portions of the genome and compare the sequences within those regions between orange and non-orange cats, looking for differences that might be the mutation that causes orange coat color,' 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.
San Francisco Chronicle
15-05-2025
- Science
- San Francisco Chronicle
Why are some cats orange? Stanford scientists solve century-old mystery
Orange cats are special — and not just because of notoriety for silly behavior. They have also been a longtime genetic enigma. Scientists have now cracked the cat color code. Two studies, published in tandem Thursday, pinpointed the gene responsible for orange cat fur. One study was led by Stanford University's School of Medicine and scientists based in the United States; the second was led by researchers in Japan. 'Over the past hundred years or so, it was recognized that orange cats kind of fall outside of the genetic rules for how coat color in mammals is determined,' said author Christopher Kaelin, a geneticist at Stanford University's School of Medicine. The investigation of felines' orange coat color addresses broader questions about animal evolution and how gene regulation is encoded in the genome, Kaelin said. Past studies pointed to the orange mutation as being on the X chromosome. By analyzing sequencing data, the American scientists further mapped the mutation to a DNA deletion near a gene called Arhgap36. In humans, increased expression of this gene has been implicated in brain tumors and endocrine cancer, according to the study. The researchers found cats with the orange mutation expressed higher levels of RNA from the Arhgap36 gene, specifically in pigment cells. They propose that the protein produced by this gene limits a step in the middle of the biological pathway behind coat color. In male cats, who typically have one X chromosome, the orange mutation means more Arhgap36 protein in pigment cells and activation of a pathway to produce reddish yellow pigment. By contrast, in male cats without the mutation, and less Arhgap36, pigment cells produce a different pigment that's black or brown. This switch recapitulates a molecular pathway in humans, in cells that make pigment that causes red hair, said author Gregory Barsh, a geneticist at Stanford University's School of Medicine and HudsonAlpha Institute for Biotechnology. Coat color is more complicated with female cats, who have two X chromosomes. A random process, known as X-chromosome inactivation, turns off one X chromosome in each cell. If a female cat has the orange mutation on just one X chromosome, this random inactivation results in a mixed tortoiseshell or calico pattern. Like the American team, the Japanese researchers identified Arhgap36 as the reason for orange cats' coat color. They additionally confirmed that the gene experiences chemical modifications that indicate it undergoes X-chromosome inactivation. 'The orange gene was a long-standing mystery for scientists,' said study author Hiroyuki Sasaki, a geneticist at Kyushu University's Institute of Bioregulation and Institute for Advanced Study, by email. 'It is a great joy for me to have finally cracked it with my colleagues.' The two studies were originally posted as preprints last year. The Japanese results were posted on Nov. 21, 2024; the American results were posted on Nov. 22, 2024. 'It's fantastic that not only one group, but two groups have published on this,' said Leslie Lyons, a feline geneticist at the University of Missouri College of Veterinary Medicine, who wasn't involved with the new studies. Lyons still wants to know more about how the genetic findings translate into the ginger hues of orange cats. One step could be quantifying how much reddish yellow pigment is produced, compared with other pigments. Another could be probing how much pigment is put into feline hairs. The U.S.-based researchers found the orange mutation specifically affected pigment cells, suggesting Arhgap36 isn't involved in orange cats' reputation for goofy behavior. Potentially, their friendly demeanors could just be a byproduct of orange cats typically being male. But there also could be linkage with some other genes, Lyons said. Scientists say orange cats' personalities could be an area for future study. 'There's a lot of anecdotal stories about orange cats and behavior, or orange cats and appetite, but those aren't well-documented in the scientific literature,' Kaelin said. 'I do think there's opportunities using citizen science approaches to make those types of associations.'
Gizmodo
15-05-2025
- Science
- Gizmodo
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.
