Tuesday, November 11, 2014

The Genetics of Cat Coats

By Brandon Keim

  
 
The Cat's Stripes


After years of studying how cats get their color, researchers have pinpointed an elusive gene underlying spots on cheetahs, stripes in house cats and patterns across the feline world. Called Taqpep, it and two other genes produce proteins central to a cascade of cell-level events that ultimately generate your kitty's distinctive coat. "It's something we've been curious about for a long time," said geneticist Stephen O'Brien of the National Cancer Institute. "We've known just three genes were involved, but nobody knew what the genes were."

Wired talks to O'Brien about the findings, which were announced Sept. 20 in Science.

Characteristic Coat Patterns

Feline coat patterns fall into two categories: stripes and spots. Though spots on a house cat may seem unusual to North American eyes, they're more common in Europe, where breeders have historically had different preferences, said O'Brien.

Earlier work by O'Brien and colleagues had pinpointed two other genes, called Agouti and Mc1r, as producing proteins that respectively control whether a coat is banded or solid, light or dark. Add Taqpep, and patterns start getting complicated.


Images: Helmi Flick

Cheetah Clues

O'Brien's team, also led by geneticists Christopher Kaelin and Greg Barsh of Stanford University, originally flagged Taqpep after comparing the genomes of regular, spotted cheetahs with rare king cheetahs, which have unusually patterned coats. They traced the physical differences, so evident in the photograph above, to a single mutation in the DNA sequence of Taqpep (below).

Images: 1) Greg Barsh/Ann van Dyk Cheetah Center 2) A spotted cheetah (at left, top sequence) compared to a king cheetah (at right, bottom sequence). (Kaelin et al./Science)

Three Mutations

Three Mutations

Inspired by the Taqpep differences between regular and king cheetahs, O'Brien and colleagues looked in the genomes of house cats, which for obvious reasons are easier to study and more abundant. They found three distinctive mutations, any of which could turn a cat from striped to splotched. "Only one mutation is required, but there are three ways to do it," O'Brien said.
Image: Helmi Flick

 Under the Skin

Under the Skin

Microscopic images of hair follicle cross-sections from cats show the tissue-scale patterning produced by Taqpep mutations. At the cell level, however, the researchers aren't yet sure what's happening. They know the genes involved, and some of the protein and molecular products, but how these interact is unknown. "We know Taqpep is a peptidase, an enzyme, a cell surface molecule that interacts with ligands," said O'Brien. "We know a little about the pathway. But the details of the physiology and the firing are not entirely clear."
Image: Kaelin et al./Science

 Testing Alan Turing

Testing Alan Turing

The great mathematician Alan Turing, best known for his accomplishments in computer science, also proposed that many natural patterns could be explained as products of what he called a reaction-diffusion system: The interplay between an "activator" chemical that makes more of itself, an "inhibitor" that slows production of the activator, and something to diffuse the chemicals.

The coats of leopards and cheetahs are considered archetypal examples of reaction-diffusion patterns, though it's still hypothetical. That may change. "Reaction-diffusion processes are a theoretical explanation for mammalian color patterns, but until molecular components of the process are identified, it is impossible to know exactly how those patterns arise," wrote study co-author Greg Barsh in an email. "Identification of Taqpeprepresents an entry point to test this idea directly.
Image: King cheetah. (Wild Cat Education and Conservation Fund)

More Than Camouflage?

More Than Camouflage?

The researchers also studied black-footed cats, a species of small, endangered feline living in southern Africa. Taqpep mutations explained their coat patterns, but their mutations' precise DNA lettering was different than in cheetahs or house cats. "These mutations occur multiple times in other species of cats, but always at different sites in the gene," said O'Brien, who finds these species-specific mutations intriguing. "The evolutionary benefit everyone always thinks of is camouflage," but he's not convinced.

O'Brien noted that the Taqpep protein, along with those produced by Agouti and Mc1r, the other coat pattern genes, belong to a unique class of proteins that move across cell membranes. Because viruses target points of potential cell entry, these transmembrane structures are often involved in immune system function.

According to O'Brien, mutations that produce coat pattern variations might also influence immune function. For now, this is just a hypothesis -- but perhaps stripes and spots have a meaning that's more than skin deep.
Image: Zbyszko/Wikimedia Commons



Citation: “Specifying and Sustaining Pigmentation Patterns in Domestic and Wild Cats.” By Christopher B. Kaelin, Xiao Xu, Lewis Z. Hong, Victor A. David, Kelly A. McGowan, Anne Schmidt-Küntzel, Melody E. Roelke, Javier Pino, Joan Pontius, Gregory M. Cooper, Hermogenes Manuel, William F. Swanson, Laurie Marker, Cindy K. Harper, Ann van Dyk,0 Bisong Yue, James C. Mullikin, Wesley C. Warren, Eduardo Eizirik, Lidia Kos, Stephen J. O’Brien, Gregory S. Barsh, Marilyn Menotti-Raymond. Science, Vol. 337 No. 6101, Sept. 19, 2012

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