What makes a tabby cat tabby?

Photo by Kattefreakske, a British Shorthair Classic Tabby

So, this is probably relevant to a few internet interests. A group of researchers have found a gene responsible for pigmentation in cats.

But wait, you say. I know this story! There’s a gene on the X-chromosome in cats that controls pigmentation, and that’s why only female cats are tortoiseshell. Haven’t we known this for a long time?

Well, yes. At least, that part of it. But in reality cat coloration is much more complicated than just tortoiseshell versus not-tortoiseshell, as anyone who is familiar with cats – such as yourselves, internet – would know. For more on what the researchers did, what they discovered, and how it fits into our understanding of cats, read below!

It turns out that cat coloration has a lot of wacky things going on. I mean, that shouldn’t surprise me too much because different cats have such different coloration. But, seriously, here are two stories of how cats are patterned:

There’s a master pigment regulator, C, which encodes a gene responsible for the very first step on the path towards pigment. And there are active, silent, and temperature-sensitive alleles of C. An active allele of C will give you dominant color. Two silent alleles will give you an albino cat. And two temperature-sensitive alleles will give you coloration in the “colder” parts of the cat: the extremities, like a Siamese cat.

By chexov from Brussels, Belgium (Flickr) [CC-BY-2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons

True story: if you make a Siamese kitten wear booties, it will have white feet when you take them off.

One gene involved in red and orange colors in cats is O, the gene on the X chromosome that makes red pigment. Since one X chromosome is randomly silenced in each cell in a female cat, and since this happens fairly early on in development and is relatively persistent throughout cell division, you get patches of cells that all came from the same ancestor-cell and all have the same color. This gene is why you get a female tortoiseshell cat, with some red and some non-red splotches.

By Riosafari (Own work) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

This cat is patterned by a bunch of cellular coin flips.

But what the researchers in question were interested in studying was patterning in the tabby cat. And here you have three-ish types: ticked, mackerel, and classic. (It gets more complicated still, and there are other genes involved that can turn a classic cat into a spotted tabby cat, or marbled, or all sorts of things. Like I said, complicated!) There’s a dominant suppressor, ticked, that causes the Abyssinian, or ticked, pattern. Then there’s the tabby gene itself, with two alleles: mackerel and blotched. Prior research had mapped that final gene – tabby, which determines the difference between a mackerel and a classic tabby cat, to a region on a single chromosome. But up until now, they haven’t been able to find tabby. They knew roughly where it was, in a region that was probably about five million bases long (they didn’t even know how long the region was because there was a gap in the cat genome). But there were no obvious genes in that region that would be involved in cat coat coloration.

Photo by Kattefreakske, a British Shorthair Classic Tabby

What’s the genetic difference between this cat and a mackerel cat?

Enter the current study. They went to spay/neuter clinics around Northern California, got samples of tissue from the largely feral cats brought into those clinics, and sequenced sequenced sequenced. They finally found a mutation in one gene that all of their blotched cats, but none of their mackerel cats, shared. (There are really several steps here; first sequencing some cats to find polymorphisms and genotyping more cats to narrow down the region to one with only three genes, and then carefully sequencing and examining those three genes to find a causative mutation.) Let me just put a personal aside here: this is really beautiful, and really foundational, genetics. This is the kind of experiment that I started doing, when I started doing genetics, something like ten years ago. And thinking about it still makes me smile.

Photo by Hampus Lybeck, a pet mouse

Admittedly, most of my work has been on these little guys.

The gene they found is kind of similar to a human gene called Aminopeptidase Q, but it has a bit that allows it to sit in a cell membrane, so they called it Transmembrane Aminopeptidase Q, or Taqpep. But the protein they call Tabulin, from tabby, because (I think) geneticists love nothing more than naming things. Especially genes.

So, they found the gene. Yay! But then they take it in a really sweet direction: they look at cheetahs. There’s this rare patterning in cheetahs where their spots sort of glomp together to make splotches. They’re called king cheetas and they look, sort of, like a tabby cat. And it turns out the same gene is responsible: the cheetah version of Taqpep is mutated in king cheetahs relative to regular cheetahs.

King Cheetah, photo by flickr user jurvetson

A king cheetah in a zoo. Notice how the spots sort of fuse together.

That’s only about half the paper. (Seriously, after that they talk about a putative master regulator called Edn3 that acts downstream of Taqpep to turn a nascent pattern encoded by which proteins are in a cell into actual pigment. It’s expressed in dark stripes in neonatal and developing cats, and in the dark spots on a cheetah, and it’s a hormone that promotes the growth of pigment-producing cells.) But even just that half is a nice story about what makes a classic tabby cat tabby, and what makes a king cheetah a king, and how certain mutations re-emerge in closely related animals to make similar patterns.

For a little bit more information, or different information, check this article in scienceNOW.

And if you’re fortunate enough to have access, and want to read the original article, go here.

Elizabeth is a PhD Candidate studying Genetics in the San Francisco Bay Area. She specializes in the epigenetics of mammalian development. In her free time, she is an aerialist, a dancer, a clothing designer, and an author. You can find her on tumblr at madgeneticist.tumblr.com, on twitter at @lysine_rich, and also on facebook or google+.

5 Comments

  1. Very interesting to the owner of a tortoiseshell (female, obviously) and a female ginger who are sisters. People keep insisting the ginger must be male because everyone KNOWS all gingers are male. I wonder what the origin of that myth is. And I had no idea torts could only be female.

  2. Now all I can think about is experimenting with the temperature-sensitive thing. Could I give it a ringed tail? Could I, say, tattoo the ears by constantly applying warmth in a particular shape? Could I stamp corporate logos onto neighbourhood cats? MILLION DOLLAR IDEA.

  3. Rachael Dunlop: So, I think the “all gingers are male” idea is just an inversion of the reality that all tortoiseshells are female (true). Thinking about the crosses, male ginger cats should be somewhat more likely than female ones, but female ginger cats are totally possible and should occur about half the time if you cross a female tortoiseshell with a male ginger.

    Quarksparrow: I know, right? So that was a weird thing that I heard in lab meeting when one of the authors of the tabby paper was presenting. I don’t think it’s perfect? And it’s possible that the effect would fade over time. But it would probably work somewhat: siamese kittens are all white, and if they live in warmer climates they stay paler. Although it would definitely be a slow effect, and would be likely to have more than a bit of blur, so I wouldn’t recommend going around, er, branding neighborhood cats.

  4. I have access to the paper, “Specifying and Sustaining
    Pigmentation Patterns in Domestic
    and Wild Cats” doi: 10.1126/science.1220893

    For those interested, the paper is available at https://docs.google.com/open?id=0ByKDdvD61XWqWWF2dndSdTd1YlU

  5. Here is a cool article on using cat coat color to teach genetics to high school and intro college students:

    http://www.genetics.org/content/155/3/999.full

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