Why Orange Cats Are Orange

00:00:17
Dr. Kaylee Byers: Hey, Sarah, we love you, but please leave the puns to the
professionals.

00:00:21
Sarah Lando: Yeah, seriously. I'm sorry. I'm sorry. I'm just feline pretty punny today.

00:00:26
Dr. Kaylee Byers: Okay, feline was pretty good. Maybe you can do them too. Based on
what you're putting down, I have a feline myself. You're about to drop some cat facts.

00:00:35
Sarah Lando: Guilty. And I want to zero in on one very particular kind of cat, the orange
cat.

00:00:42
Dr. Kaylee Byers: I love orange cats. In fact, I have an orange cat, so I can't wait to
hear about this.

00:00:46
Sarah Lando: I did not know that.

00:00:47
Dr. Kaylee Byers: Yeah. Gizmo.

00:00:48
Sarah Lando: Gizmo. So cute. So Gizmo's bright color is actually something that has
stumped scientists for a long time. And we've only just figured out why orange cats are
well orange.

00:01:03
Dr. Kaylee Byers: Okay. Well, don't leave me in suspense. Why are they orange?

00:01:06
Sarah Lando: So just a little background info, roughly 80% of orange cats are male and
this sex based color difference is unique to cats. And other orange or red colored
mammals like orangutans, foxes, or golden retrievers, there's no male bias. In most
mammals, including humans, red or orange coloring is caused by mutations in a single
pigment related gene called the MC1R gene.

00:01:31
Dr. Kaylee Byers: I love this because my cat is actually a female and she's orange, and
I know that that's bizarre. So what is going on with our orange friends?

00:01:41
Sarah Lando: So in cats, the strong male bias means MC1R can't be the whole story.
Because the color pattern tracks with sex, the orange gene has to be on the X
chromosome. Males only have one X chromosome. So if a single X carries the orange
mutation, they're fully orange, whereas females have two X chromosomes and would
need the orange mutation on both chromosomes to be fully orange. So the big question
is, which gene on the X chromosome actually does it? And solving that mystery took
about 60 years until now.

00:02:16
Dr. Kaylee Byers: I love the idea of someone spending 60 years on this question.

00:02:19
Sarah Lando: Right.

00:02:19
Dr. Kaylee Byers: Just one person.

00:02:20
Sarah Lando: Yeah.

00:02:22
Dr. Kaylee Byers: Just so dedicated. I have to sort this out.

00:02:25
Sarah Lando: So in late 2024, two independent research teams, one from Stanford
University in the US and another from Kyushu University in Japan finally cracked the
mystery at almost the exact same time. What both teams found by using genomics was
a small missing chunk of DNA found on the X chromosome of orange cats. That missing
piece sits right next to a gene called ARHGAP36. A gene usually involved in
development and even linked to cancer, but it doesn't usually have anything to do with
pigment cells.

00:03:01
Dr. Kaylee Byers: That's wild. So you said in other animals that's usually MC1R.

00:03:05
Sarah Lando: Exactly. Normally, when there isn't a missing chunk of DNA, there's a
kind of genetic fence that keeps the ARHGAP36 gene turned off in skin and fur cells.
But in orange cats, that little deletion removes that fence. And as a result, ARHGAP36
switches on where it shouldn't. And when it turns on, it disrupts the usual pigment
pathway, pushing the pigment cells to make red yellow pigment instead of dark brown
or black. The Stanford team found that every orange, calico and tortoiseshell cat shared
this exact DNA deletion. The Kyushu team confirmed it too across more than 280 cats
from around the world.

00:03:49
Dr. Kaylee Byers: So this one little missing piece of DNA is basically what's making
Garfield orange.

00:03:54
Sarah Lando: Yeah, pretty much. So let's talk about why this is so cool. Scientists are
fascinated by this finding because this mutation breaks the usual rules. Usually when a
piece of DNA is deleted, it reduces or disrupts gene activity nearby. But in orange cats,
the deletion does the exact opposite. It actually switches on ARHGAP36 in pigment

cells where the gene is normally silent. And this is not typical for deletions. Researchers
say it suggests there's something really unique, maybe even special about cats. It
shows how a small change in DNA can unlock a totally unexpected biological outcome.
Discoveries like this expand our understanding of how new traits can evolve. And
because this exact mutation shows up in orange, calico, and tortoiseshell cats all over
the world, it likely emerged early in cat history and stuck around, which is why ancient
art already shows cats with these colors.

00:04:53
Dr. Kaylee Byers: Well, Sarah, that's a pretty good yarn. I'm 100% going to use this
little piece of cat trivia at the next dinner party when I talk about why my cat is better
than all other cats. So thank you so much for sharing that with us.

00:05:05
Sarah Lando: Always a pleasure and thanks for having me, Kaylee. This was so fun.

00:05:09
Dr. Kaylee Byers: Well, obviously. This podcast is a delight and thanks for coming on
to end this season with a cat themed minisode. That is a wrap on our pocket sized
Gene Shorts for the season. Sad, I know, but don't worry. We've still got one more
genomic repeat we handpicked from deep in the nice genes drawer. And if you've got a
second, don't forget to leave us a review. We love hearing from you and what you think
about the show. I'm Dr. Kaylee Byers, and as always, thank mew very much for
listening.

00:05:37
Sarah Lando: Purrfect.

00:05:37
Dr. Kaylee Byers: Purrfect.